Molecules

2024

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11 pages, 1069 KiB

Open AccessArticle

Stilbenes in Carex acuta and Carex lepidocarpa

by Jan Tříska, Naděžda Vrchotová, Štěpán Horník, Jan Sýkora and Andrea Kučerová

Molecules 2024, 29(16), 3840; https://doi.org/10.3390/molecules29163840 - 13 Aug 2024

Viewed by 535

Abstract

Stilbenes in the roots of Carex acuta and Carex lepidocarpa were studied. Root samples were extracted with 100% methanol and analyzed by HPLC and LC-MS. In this way, trans-resveratrol dimers (m/z 455 Da [M + H]⁺), trimers [...] Read more.

Stilbenes in the roots of Carex acuta and Carex lepidocarpa were studied. Root samples were extracted with 100% methanol and analyzed by HPLC and LC-MS. In this way, trans-resveratrol dimers (m/z 455 Da [M + H]⁺), trimers (m/z 681 Da [M + H]⁺) and tetramers (m/z 907 Da [M + H]⁺) were identified in the extracts. Using LC-NMR in stop-flow mode, pallidol and trans-ε-viniferin as dimers were identified. After the separation of individual peaks and their measurement by ¹H NMR, cis and trans-miyabenol A as a tetramer and cis-miyabenol C as a trimer were identified. In the case of miyabenol A, it is a chromatographically inseparable mixture of cis and trans isomers in the ratio of 2:3 according to ¹H NMR measurement. In the case of cis-miyabenol C, the Z-trans-trans-miyabenol C configuration was confirmed. The remaining unidentified peak with a practically identical UV-VIS spectrum to that of cis-miyabenol C is most likely another isomer of miyabenol C. Full article

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15 pages, 3563 KiB

Open AccessArticle

Pleurotus sajor-caju (Fr.) Singer β-1,3-Glucanoligosaccharide (Ps-GOS) Suppresses RANKL-Induced Osteoclast Differentiation and Function in Pre-Osteoclastic RAW 264.7 Cells by Inhibiting the RANK/NFκB/cFOS/NFATc1 Signalling Pathway

by Purithat Rattajak, Aratee Aroonkesorn, Carl Smythe, Rapepun Wititsuwannakul and Thanawat Pitakpornpreecha

Molecules 2024, 29(9), 2113; https://doi.org/10.3390/molecules29092113 - 2 May 2024

Viewed by 1451

Abstract

Edible grey oyster mushroom, Pleurotus sajor-caju, β (1,3), (1,6) glucan possesses a wide range of biological activities, including anti-inflammation, anti-microorganism and antioxidant. However, its biological activity is limited by low water solubility resulting from its high molecular weight. Our previous study demonstrated [...] Read more.

Edible grey oyster mushroom, Pleurotus sajor-caju, β (1,3), (1,6) glucan possesses a wide range of biological activities, including anti-inflammation, anti-microorganism and antioxidant. However, its biological activity is limited by low water solubility resulting from its high molecular weight. Our previous study demonstrated that enzymatic hydrolysis of grey oyster mushroom β-glucan using Hevea β-1,3-glucanase isozymes obtains a lower molecular weight and higher water solubility, Pleurotus sajor-caju glucanoligosaccharide (Ps-GOS). Additionally, Ps-GOS potentially reduces osteoporosis by enhancing osteoblast–bone formation, whereas its effect on osteoclast–bone resorption remains unknown. Therefore, our study investigated the modulatory activities and underlying mechanism of Ps-GOS on Receptor activator of nuclear factor kappa-Β ligand (RANKL) -induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. Cell cytotoxicity of Ps-GOS on RAW 264.7 cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and its effect on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining. Additionally, its effect on osteoclast bone-resorptive ability was detected by pit formation assay. The osteoclastogenic-related factors were assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), Western blot and immunofluorescence. The results revealed that Ps-GOS was non-toxic and significantly suppressed the formation of mature osteoclast multinucleated cells and their resorption activity by reducing the number of TRAP-positive cells and pit formation areas in a dose-dependent manner. Additionally, Ps-GOS attenuated the nuclear factor kappa light chain-enhancer of activated B cells’ P65 (NFκB-P65) expression and their subsequent master osteoclast modulators, including nuclear factor of activated T cell c1 (NFATc1) and Fos proto-oncogene (cFOS) via the NF-κB pathway. Furthermore, Ps-GOS markedly inhibited RANK expression, which serves as an initial transmitter of many osteoclastogenesis-related cascades and inhibited proteolytic enzymes, including TRAP, matrix metallopeptidase 9 (MMP-9) and cathepsin K (CTK). These findings indicate that Ps-GOS could potentially be beneficial as an effective natural agent for bone metabolic disease. Full article

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2023

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12 pages, 1536 KiB

Open AccessArticle

Toxicity and Repellency Efficacy of Benzyl Alcohol and Benzyl Benzoate as Eco-Friendly Choices to Control the Red Flour Beetle Tribolium castaneum (Herbst. 1797)

by Shawky M. Aboelhadid, Samar M. Ibrahium, Heba Abdel-Tawab, Ahmed O. Hassan, Saleh Al-Quraishy, Fatma El-zahraa R. Saleh and Abdel-Azeem S. Abdel-Baki

Molecules 2023, 28(23), 7731; https://doi.org/10.3390/molecules28237731 - 23 Nov 2023

Cited by 4 | Viewed by 1822

Abstract

Tribolium castaneum is a damaging pest of stored grains, causing significant losses and secreting lethal quinones, which render the grains unfit for human consumption. Chemical insecticides are the most commonly used approach for control; however, they create insecticide resistance and affect the health [...] Read more.

Tribolium castaneum is a damaging pest of stored grains, causing significant losses and secreting lethal quinones, which render the grains unfit for human consumption. Chemical insecticides are the most commonly used approach for control; however, they create insecticide resistance and affect the health of humans, animals, and the environment. As a result, it is critical to find an environmentally friendly pest-management strategy. In this study, two naturally occurring chemicals, benzyl alcohol (BA) and benzoyl benzoate (BB), were investigated for insecticidal activity against T. castaneum using different assays (impregnated-paper, contact toxicity, fumigant, and repellency assays). The results showed that BA had a significant insecticidal effect, with the LC₅₀ achieved at a lower concentration in the direct-contact toxicity test (1.77%) than in the impregnated-paper assay (2.63%). BB showed significant effects in the direct-contact toxicity test, with an LC₅₀ of 3.114%, and a lower toxicity in the impregnated-paper assay, with an LC₅₀ of 11.75%. Furthermore, BA exhibited significant fumigant toxicity against T. castaneum, with an LC₅₀ of 6.72 µL/L, whereas BB exhibited modest fumigant toxicity, with an LC₅₀ of 464 µL/L. Additionally, at different concentrations (0.18, 0.09, 0.045, and 0.0225 µL/cm²), BA and BB both showed a notable and potent repelling effect. BA and BB significantly inhibited acetylcholinesterase, reduced glutathione (GSH), and increased malondialdehyde (MDA) in treated T. castaneum. This is the first report of BA insecticidal activity against the red flour beetle. Also, the outcomes of various assays demonstrated that the application of BA induces a potent bio-insecticidal effect. BA may be a promising eco-friendly alternative to control T. castaneum due to its safety and authorization by the EFSA (European Food Safety Authority). Full article

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13 pages, 1283 KiB

Open AccessArticle

Computer Analysis of the Inhibition of ACE2 by Flavonoids and Identification of Their Potential Antiviral Pharmacophore Site

by Andrey Bogoyavlenskiy, Madina Alexyuk, Pavel Alexyuk, Vladimir Berezin, Faisal A. Almalki, Taibi Ben Hadda, Alaa M. Alqahtani, Saleh A. Ahmed, Stefano Dall’Acqua and Joazaizulfazli Jamalis

Molecules 2023, 28(9), 3766; https://doi.org/10.3390/molecules28093766 - 27 Apr 2023

Cited by 2 | Viewed by 2277

Abstract

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory [...] Read more.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time. Full article

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2022

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14 pages, 629 KiB

Open AccessCommunication

Comment on Pyrrolizidine Alkaloids and Terpenes from Senecio (Asteraceae): Chemistry and Research Gaps in Africa

by Nicholas John Sadgrove

Molecules 2022, 27(24), 8868; https://doi.org/10.3390/molecules27248868 - 13 Dec 2022

Cited by 3 | Viewed by 1986

Abstract

The genus Senecio is one of the largest in Asteraceae. There are thousands of species across the globe, either confirmed or awaiting taxonomic delimitation. While the species are best known for the toxic pyrrolizidine alkaloids that contaminate honeys (as bees select pollen from [...] Read more.

The genus Senecio is one of the largest in Asteraceae. There are thousands of species across the globe, either confirmed or awaiting taxonomic delimitation. While the species are best known for the toxic pyrrolizidine alkaloids that contaminate honeys (as bees select pollen from the species) and teas via lateral transfer and accumulation from adjacent roots of Senecio in the rhizosphere, they are also associated with more serious cases leading to fatality of grazing ruminants or people by contamination or accidental harvesting for medicine. Surprisingly, there are significantly more sesquiterpenoid than pyrrolizidine alkaloid-containing species. The main chemical classes, aside from alkaloids, are flavonoids, cacalols, eremophilanes, and bisabolols, often in the form of furan derivatives or free acids. The chemistry of the species across the globe generally overlaps with the 469 confirmed species of Africa. A small number of species express multiple classes of compounds, meaning the presence of sesquiterpenes does not exclude alkaloids. It is possible that there are many species that express the pyrrolizidine alkaloids, in addition to the cacalols, eremophilanes, and bisabolols. The aim of the current communication is, thus, to identify the research gaps related to the chemistry of African species of Senecio and reveal the possible chemical groups in unexplored taxa by way of example, thereby creating a summary of references that could be used to guide chemical assignment in future studies. Full article

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3 pages, 635 KiB

Open AccessCorrection

Correction: Wang et al. Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum acmosepalum. Molecules 2019, 24, 50

by Jiao Wang, Mengjiao Shi, Jiajia Wang, Jin Li and Tengfei Ji

Molecules 2022, 27(13), 3986; https://doi.org/10.3390/molecules27133986 - 21 Jun 2022

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Abstract

The authors wish to make the following correction to their paper [...] Full article

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13 pages, 1152 KiB

Open AccessArticle

Bromatological Analysis and Characterization of Phenolics in Snow Mountain Garlic

by Yolanda Terán-Figueroa, Denisse de Loera, Alberto Toxqui-Terán, Gabriela Montero-Morán and María Zenaida Saavedra-Leos

Molecules 2022, 27(12), 3712; https://doi.org/10.3390/molecules27123712 - 9 Jun 2022

Cited by 1 | Viewed by 2729

Abstract

The remarkable properties of garlic A. sativum L. have been described, but little is known about Snow mountain garlic. Understanding general aspects of this garlic composition, including the presence of phenolics, will establish its possible use for health or infer which compounds can [...] Read more.

The remarkable properties of garlic A. sativum L. have been described, but little is known about Snow mountain garlic. Understanding general aspects of this garlic composition, including the presence of phenolics, will establish its possible use for health or infer which compounds can contribute to improving it. This study aimed to determine the ash content, lipid profile, and characterization of phenolics in Snow mountain garlic. The organic content was obtained by common techniques (oven drying, calcination, Kjeldahl method, etc.). The quantitative analysis of the ashes was made by Inductively Coupled Plasma Emission Spectrometry. The fatty acid profile was determined by Gas Chromatography. The presence of phenolics was determined by foam, Libermann–Burchard, Dragendorff, Salkowski, ferric chloride, vanillin, catechin, Constantinescu, and Shinoda reactions. The total phenolic content was determined via the Folin–Ciocalteu method, and antioxidant activity was determined using the DPPH radical method. The bromatological analysis showed a 51.1% humidity, and the main organic compounds were carbohydrates (46.7%). Ash analysis showed 287.46 g/kg of potassium. The fatty acid profile showed 75.61% of polyunsaturated fatty acid. Phenolics like saponins, alkaloids, triterpenes, tannins, and flavonoids were present. Antioxidant activity was found by radical DPPH of 25.64 (±0.78) µmol TE/1 g dw. Snow mountain garlic shares a composition similar to those found in other garlic. Full article

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14 pages, 1014 KiB

Open AccessArticle

Monoterpenoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities

by Shi-Hui Lu, Jing Huang, Hao-Jiang Zuo, Zhong-Bo Zhou, Cai-Yan Yang and Zu-Liang Huang

Molecules 2022, 27(12), 3709; https://doi.org/10.3390/molecules27123709 - 9 Jun 2022

Cited by 6 | Viewed by 1870

Abstract

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat, remove toxins, and treat obesity and diabetes, in Southwest China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of eight [...] Read more.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat, remove toxins, and treat obesity and diabetes, in Southwest China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of eight new monoterpenoid glycosides (1–8) and three known monoterpenoid glycosides (9–11). Compounds 1–11 were tested for the inhibitory activities on fatty acid synthase (FAS), α-glucosidase, α-amylase, and the antioxidant effects. Compound 2 showed stronger FAS inhibitory activity (IC₅₀: 2.36 ± 0.10 μM) than the positive control orlistat (IC₅₀: 4.46 ± 0.13 μM), while compounds 1, 2, 5 and 11 displayed more potent ABTS radical scavenging activity (IC₅₀: 6.91 ± 0.10~9.41 ± 0.22 μM) than the positive control L-(+)-ascorbic acid (IC₅₀: 10.06 ± 0.19 μM). This study provided a theoretical basis for the leaves of L. robustum as a functional tea to treat obesity. Full article

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13 pages, 2934 KiB

Open AccessArticle

Saprophytic Bacillus Accelerates the Release of Effective Components in Agarwood by Degrading Cellulose

by Huizhen Yang, Runying He, Yao Cui, Ying Li and Xizhen Ge

Molecules 2022, 27(4), 1428; https://doi.org/10.3390/molecules27041428 - 20 Feb 2022

Cited by 3 | Viewed by 2891

Abstract

The value of Agarwood increases with time due to the gradual release of its major components, but the mechanism behind this remains unclear. Herein we reveal that the potential driving force of this process is the degradation of cellulose in Agarwood by its [...] Read more.

The value of Agarwood increases with time due to the gradual release of its major components, but the mechanism behind this remains unclear. Herein we reveal that the potential driving force of this process is the degradation of cellulose in Agarwood by its saprophytic Bacillus subtilis. We selected 10-year-old Agarwood from different places and then isolated the saprophytic bacteria. We confirmed these bacteria from different sources are all Bacillus and confirmed they can degrade cellulose, and the highest cellulase activity reached 0.22 U/mL. By co-cultivation of the bacterium and Agarwood powder, we found that three of the strains could release the effective components of Agarwood, while they had little effect in increasing the same components in living Aquilaria sinensis. Finally, we demonstrated that these saprophytic Bacillus subtilis have similar effects on Zanthoxylum bungeanum Maxim and Dalbergiaod orifera T. Chen, but not on Illicium verum Hook. f, Cinnamomum cassia Presl and Phellodendron chinense Schneid. In conclusion, our experiment revealed that the saprophytic Bacillus release the effective components of Agarwood by degrading cellulose, and we provide a promising way to accelerate this process by using this bacterial agent. Full article

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19 pages, 2152 KiB

Open AccessArticle

In Vivo Anti-Inflammatory Effect, Antioxidant Activity, and Polyphenolic Content of Extracts from Capsicum chinense By-Products

by Lilian Dolores Chel-Guerrero, Gabriela Castañeda-Corral, Misael López-Castillo, Matteo Scampicchio, Ksenia Morozova, Julio Enrique Oney-Montalvo, Giovanna Ferrentino, Juan José Acevedo-Fernández and Ingrid Mayanín Rodríguez-Buenfil

Molecules 2022, 27(4), 1323; https://doi.org/10.3390/molecules27041323 - 16 Feb 2022

Cited by 14 | Viewed by 3932

Abstract

By-products of Capsicum chinense Jacq., var Jaguar could be a source of bioactive compounds. Therefore, we evaluated the anti-inflammatory effect, antioxidant activity, and their relationship with the polyphenol content of extracts of habanero pepper by-products obtained from plants grown on black or red [...] Read more.

By-products of Capsicum chinense Jacq., var Jaguar could be a source of bioactive compounds. Therefore, we evaluated the anti-inflammatory effect, antioxidant activity, and their relationship with the polyphenol content of extracts of habanero pepper by-products obtained from plants grown on black or red soils of Yucatán, Mexico. Moreover, the impact of the type of extraction on their activities was evaluated. The dry by-product extracts were obtained by maceration (ME), Soxhlet (SOX), and supercritical fluid extraction (SFE). Afterward, the in vivo anti-inflammatory effect (TPA-induced ear inflammation) and the in vitro antioxidant activity (ABTS) were evaluated. Finally, the polyphenolic content was quantified by Ultra-Performance Liquid Chromatography (UPLC), and its correlation with both bioactivities was analyzed. The results showed that the SFE extract of stems of plants grown on red soil yielded the highest anti-inflammatory effect (66.1 ± 3.1%), while the extracts obtained by ME and SOX had the highest antioxidant activity (2.80 ± 0.0052 mM Trolox equivalent) and polyphenol content (3280 ± 15.59 mg·100 g⁻¹ dry basis), respectively. A negative correlation between the anti-inflammatory effect, the antioxidant activity, and the polyphenolic content was found. Overall, the present study proposed C. chinense by-products as a valuable source of compounds with anti-inflammatory effect and antioxidant activity. Full article

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12 pages, 2942 KiB

Open AccessArticle

Effects of Physical Properties and Processing Methods on Astragaloside IV and Flavonoids Content in Astragali radix

by Mei-Yin Chien, Chih-Min Yang and Chao-Hsiang Chen

Molecules 2022, 27(2), 575; https://doi.org/10.3390/molecules27020575 - 17 Jan 2022

Cited by 7 | Viewed by 2366

Abstract

The aim of this study was to investigate the effects of the physical properties (diameter size, powder particle size, composition of bark- and wood-tissue, and turnover rate) and processing methods on the content of active ingredients in Astragali radix (AR), a popular Chinese [...] Read more.

The aim of this study was to investigate the effects of the physical properties (diameter size, powder particle size, composition of bark- and wood-tissue, and turnover rate) and processing methods on the content of active ingredients in Astragali radix (AR), a popular Chinese herbal medicine. The astragaloside IV and flavonoid contents increased with decreasing diameter size. Bark-tissue had significantly higher astragaloside IV and formononetin content than that in the wood-tissue. As a higher proportion of bark-tissue is associated with decreasing diameter, a strong correlation was also shown between bark- to wood-tissue ratio and active ingredients’ content. Furthermore, an increase in astragaloside IV content was observed in thin powder as compared to coarse powder ground from the whole root. However, this association between active ingredients’ content and powder particle size was abolished when isolating bark- and wood-tissue individually. Moreover, AR stir-frying with refined honey, a typical processing method of AR, increased formononetin content. The turnover rate of active constituents upon decoction ranged from 61.9–81.4%. Assessing the active constituent contents using its physical properties and processing methods allows for a more comprehensive understanding of optimizing and strengthening the therapeutic potentials of AR used in food and herbal supplements. Full article

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2021

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18 pages, 2489 KiB

Open AccessArticle

Antibacterial Activities of Prenylated Isoflavones from Maclura tricuspidata against Fish Pathogenic Streptococcus: Their Structure-Activity Relationships and Extraction Optimization

by Jae-Woong Lim, Yang Hee Jo, Ji-Seok Choi, Mi Kyeong Lee, Ki Yong Lee and So Young Kang

Molecules 2021, 26(24), 7451; https://doi.org/10.3390/molecules26247451 - 9 Dec 2021

Cited by 9 | Viewed by 2133

Abstract

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an [...] Read more.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95–500 μg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part’s antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box–Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture. Full article

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13 pages, 840 KiB

Open AccessArticle

Effect of Edible Onion (Allium cepa L.) Film on Quality, Sensory Properties and Shelf Life of Beef Burger Patties

by Kallyne Sousa Soares, Marthyna Pessoa Souza, Edson C. Silva-Filho, Hernane Silva Barud, Clóvis Augusto Ribeiro, Diógenes Dias Santos, Karla Nayalle Souza Rocha, José Fabio Paulino de Moura, Ronaldo Lopes Oliveira and Leilson Rocha Bezerra

Molecules 2021, 26(23), 7202; https://doi.org/10.3390/molecules26237202 - 27 Nov 2021

Cited by 13 | Viewed by 3891

Abstract

The production of edible film from onion (Allium cepa L.) to be applied as packaging is attractive, due to its chemical properties and biodegradable characteristics. Thus, we tested the hypothesis that edible onion film can positively influence the sensory properties, quality and [...] Read more.

The production of edible film from onion (Allium cepa L.) to be applied as packaging is attractive, due to its chemical properties and biodegradable characteristics. Thus, we tested the hypothesis that edible onion film can positively influence the sensory properties, quality and increasing shelf life of beef burgers patties. The experiment was designed in a 4 × 2 factorial scheme, with two treatments (beef burgers patties with or without edible onion film) at an interval of four storage times (0, 3, 6 and 9 days) at 4 °C. The uncoated burger patties (control) suffered the most intense color modifications during the storage (p < 0.05). The luminosity index was higher (p < 0.05) in the control at all storage times, except at day 6, and redness, yellowness and chrome were higher (p < 0.05) in the edible onion film patties at all storage times. The pH of the beef burger patties was lower (p < 0.05) at all storage times when the edible onion film was applied. For the texture profile, only the chewiness was affected, as the inclusion of the edible onion film improved the chewing of the beef burgers patties over the storage time (p < 0.05). Additionally, there was an inhibition of the microbial growth of mesophiles and psychrophiles with the application of the edible onion film in beef burgers patties. The use of edible onion film improved the perception of panelists for the variables texture, color, flavor, odor and overall appearance, and increased the preference of panelists. The edible onion film is recommended for preserving beef burgers patties, as it delays the proliferation of unwanted microorganisms, stabilizes and improves the color parameters and sensory attributes, and increases the overall acceptance of the consumer. Full article

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12 pages, 285 KiB

Open AccessArticle

Chemical Composition and Biological Activities of Essential Oils from the Leaves, Stems, and Roots of Kadsura coccinea

by Tianming Zhao, Chao Ma and Guofei Zhu

Molecules 2021, 26(20), 6259; https://doi.org/10.3390/molecules26206259 - 16 Oct 2021

Cited by 12 | Viewed by 2780

Abstract

The chemical composition and biological activities of the essential oils from the leaves, stems, and roots of Kadsura coccinea (K. coccinea) were investigated. The essential oils were extracted by hydro distillation and analyzed by gas chromatography mass spectrometry (GC-MS) and gas [...] Read more.

The chemical composition and biological activities of the essential oils from the leaves, stems, and roots of Kadsura coccinea (K. coccinea) were investigated. The essential oils were extracted by hydro distillation and analyzed by gas chromatography mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Antioxidant activities of the essential oils were examined with DPPH radical scavenging assay, ABTS cation radical scavenging assay, and ferric reducing antioxidant power assay. Antimicrobial activities were evaluated by determining minimum inhibitory concentrations (MIC) and minimum microbiocidal concentrations (MMC). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of the essential oils were also tested. A total of 46, 44, and 47 components were identified in the leaf, stem, and root oils, representing 95.66%, 97.35%, and 92.72% of total composition, respectively. The major compounds of three essential oils were α-pinene (16.60–42.02%), β-pinene (10.03–18.82%), camphene (1.56–10.95%), borneol (0.50–7.71%), δ-cadinene (1.52–7.06%), and β-elemene (1.86–4.45%). The essential oils were found to have weak antioxidant activities and cholinesterase inhibition activities. The essential oils showed more inhibitory effects against Staphylococcus aureus (S. aureus) than those of other strains. The highest antimicrobial activity was observed in the root oil against S. aureus, with MIC of 0.78 mg/mL. Therefore, K. coccinea essential oils might be considered as a natural antibacterial agent against S. aureus with potential application in food and pharmaceutical industries. Full article

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16 pages, 1646 KiB

Open AccessArticle

Apigenin Ameliorates Scopolamine-Induced Cognitive Dysfunction and Neuronal Damage in Mice

by Yeojin Kim, Jihyun Kim, Meitong He, Ahyoung Lee and Eunju Cho

Molecules 2021, 26(17), 5192; https://doi.org/10.3390/molecules26175192 - 27 Aug 2021

Cited by 28 | Viewed by 4849

Abstract

We investigated the protective effect and mechanisms of apigenin against cognitive impairments in a scopolamine-injected mouse model. Our results showed that intraperitoneal (i.p.) injection of scopolamine leads to learning and memory dysfunction, whereas the administration of apigenin (synthetic compound, 100 and 200 mg/kg/day) [...] Read more.

We investigated the protective effect and mechanisms of apigenin against cognitive impairments in a scopolamine-injected mouse model. Our results showed that intraperitoneal (i.p.) injection of scopolamine leads to learning and memory dysfunction, whereas the administration of apigenin (synthetic compound, 100 and 200 mg/kg/day) improved cognitive ability, which was confirmed by behavioral tests such as the T-maze test, novel objective recognition test, and Morris water maze test in mice. In addition, scopolamine-induced lipid peroxidation in the brain was attenuated by administration of apigenin. To further evaluate the protective mechanisms of apigenin on cognitive and memory function, Western blot analysis was carried out. Administration of apigenin decreased the B-cell lymphoma 2-associated X/B-cell lymphoma 2 (Bax/Bcl-2) ratio and suppressed caspase-3 and poly ADP ribose polymerase cleavage. Furthermore, apigenin down-regulated the β-site amyloid precursor protein-cleaving enzyme, along with presenilin 1 (PS1) and PS2 protein levels. Apigenin-administered mice showed lower protein levels of a receptor for advanced glycation end-products, whereas insulin-degrading enzyme, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) expression were promoted by treatment with apigenin. Therefore, this study demonstrated that apigenin is an active substance that can improve cognitive and memory functions by regulating apoptosis, amyloidogenesis, and BDNF/TrkB signaling pathways. Full article

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9 pages, 261 KiB

Open AccessArticle

Cardioprotective Potential of Garlic Oil and Its Active Constituent, Diallyl Disulphide, in Presence of Carvedilol during Chronic Isoprenaline Injection-Mediated Myocardial Necrosis in Rats

by Syed Mohammed Basheeruddin Asdaq, Abdulhakeem S. Alamri, Walaa F. Alsanie and Majid Alhomrani

Molecules 2021, 26(17), 5137; https://doi.org/10.3390/molecules26175137 - 25 Aug 2021

Cited by 9 | Viewed by 2667

Abstract

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with [...] Read more.

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR’s cardioprotective impact and protected rats from developing ISO-induced myocardial infarction. Full article

19 pages, 2013 KiB

Open AccessArticle

Chemical Constitution and Antimicrobial Activity of Kombucha Fermented Beverage

by Abdul-Raouf Al-Mohammadi, Ahmed A. Ismaiel, Rehab A. Ibrahim, Ahmed H. Moustafa, Azza Abou Zeid and Gamal Enan

Molecules 2021, 26(16), 5026; https://doi.org/10.3390/molecules26165026 - 19 Aug 2021

Cited by 40 | Viewed by 7555

Abstract

Kombucha is a traditional beverage of sweetened black tea fermented with a symbiotic association of acetic acid bacteria and yeasts. In this study, kombucha fermented beverage (KFB) appeared to include nine chemical groups (alcohols, acids, lactones, condensed heterocyclic compounds, antibiotics, esters, aldehydes, fatty [...] Read more.

Kombucha is a traditional beverage of sweetened black tea fermented with a symbiotic association of acetic acid bacteria and yeasts. In this study, kombucha fermented beverage (KFB) appeared to include nine chemical groups (alcohols, acids, lactones, condensed heterocyclic compounds, antibiotics, esters, aldehydes, fatty acids, and alkaloids) of many bioactive metabolites, as elucidated by gas chromatography–mass spectrometry (GC-MS) and IR spectra. The fermented metabolic components of KFB seem collectively to act in a synergistic action giving rise to the antimicrobial activity. Four types of kombucha preparations (fermented, neutralized, heat-treated and unfermented) were demonstrated with respect to their antimicrobial activity against some pathogenic bacterial and fungal strains using agar well diffusion assay. KFB exerted the strongest antimicrobial activities when compared with neutralized and heat-treated kombucha beverages (NKB and HKB). Staphylococcus aureus ATCC6538 (S. aureus) and Escherichia coli ATCC11229 (E. coli) were the organisms most susceptible to the antimicrobial activity of kombucha beverage preparations. Finally, the KFB preparation showed remarkable inhibitory activity against S. aureus and E. coli bacteria in a brain heart infusion broth and in some Egyptian fruit juices (apple, guava, strawberry, and tomato). These data reveal that kombucha is not only a prophylactic agent, but also appears to be promising as a safe alternative biopreservative, offering protection against pathogenic bacteria and fungi. Full article

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10 pages, 7476 KiB

Open AccessArticle

Amber Extract Reduces Lipid Content in Mature 3T3-L1 Adipocytes by Activating the Lipolysis Pathway

by Erica Sogo, Siqi Zhou, Haruna Haeiwa, Reiko Takeda, Kazuma Okazaki, Marie Sekita, Takuya Yamamoto, Mikio Yamano and Kazuichi Sakamoto

Molecules 2021, 26(15), 4630; https://doi.org/10.3390/molecules26154630 - 30 Jul 2021

Cited by 11 | Viewed by 2873

Abstract

Amber—the fossilized resin of trees—is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. [...] Read more.

Amber—the fossilized resin of trees—is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases. Full article

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17 pages, 1609 KiB

Open AccessArticle

Determination of Triterpenoids and Phenolic Acids from Sanguisorba officinalis L. by HPLC-ELSD and Its Application

by Jiahui Sun, Chunli Gan, Jing Huang, Zhenyue Wang, Chengcui Wu, Shuang Jiang, Xinrong Yang, Hesong Peng, Fanshu Wei and Chunjuan Yang

Molecules 2021, 26(15), 4505; https://doi.org/10.3390/molecules26154505 - 27 Jul 2021

Cited by 8 | Viewed by 2727

Abstract

A novel analytical method involving high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for simultaneous determination of 11 phenolic acids and 12 triterpenes in Sanguisorba officinalis L. Chromatographic separation was conducted with gradient elution mode by using a Diamonsil^TM [...] Read more.

A novel analytical method involving high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for simultaneous determination of 11 phenolic acids and 12 triterpenes in Sanguisorba officinalis L. Chromatographic separation was conducted with gradient elution mode by using a Diamonsil^TM C₁₈ column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.1% acetic acid water (A) and methanol (B). The drift tube temperature of ELSD was set at 70 °C and the nitrogen cumulative flow rate was 1.6 L/min. The method was fully validated to be linear over a wide concentration range (R² ≥ 0.9991). The precisions (RSD) were less than 3.0% and the recoveries were between 97.7% and 101.4% for all compounds. The results indicated that this method is accurate and effective for the determination of 23 functional components in Sanguisorba officinalis L. and could also be successfully applied to study the influence of processing method on those functional components in Sanguisorba officinalis L. Full article

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12 pages, 2801 KiB

Open AccessArticle

Antifungal Activities of cis-trans Citral Isomers against Trichophyton rubrum with ERG6 as a Potential Target

by Yin Zheng, Yanhong Shang, Mengyun Li, Yunzhou Li and Wuqing Ouyang

Molecules 2021, 26(14), 4263; https://doi.org/10.3390/molecules26144263 - 14 Jul 2021

Cited by 19 | Viewed by 2779

Abstract

Trichophyton rubrum causes ringworm worldwide. Citral (CIT), extracted from Pectis plants, is a monoterpene and naturally composed of geometric isomers neral (cis-citral) and geranial (trans-citral). CIT has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. [...] Read more.

Trichophyton rubrum causes ringworm worldwide. Citral (CIT), extracted from Pectis plants, is a monoterpene and naturally composed of geometric isomers neral (cis-citral) and geranial (trans-citral). CIT has promising antifungal activities and ergosterol biosynthesis inhibition effects against several pathogenic fungi. However, no study has focused on neral and geranial against T. rubrum, which hinders the clinical application of CIT. This study aimed to compare antifungal activities of neral and geranial and preliminarily elucidate their ergosterol biosynthesis inhibition mechanism against T. rubrum. Herein, the disc diffusion assays, cellular leakage measurement, flow cytometry, SEM/TEM observation, sterol quantification, and sterol pattern change analyses were employed. The results showed geranial exhibited larger inhibition zones (p < 0.01 or 0.05), higher cellular leakage rates (p < 0.01), increased conidia with damaged membranes (p < 0.01) within 24 h, more distinct shriveled mycelium in SEM, prominent cellular material leakage, membrane damage, and morphological changes in TEM. Furthermore, geranial possessed more promising ergosterol biosynthesis inhibition effects than neral, and both induced the synthesis of 7-Dehydrodesmosterol and Cholesta-5,7,22,24-tetraen-3β-ol, which represented marker sterols when ERG6 was affected. These results suggest geranial is more potent than neral against T. rubrum, and both inhibit ergosterol biosynthesis by affecting ERG6. Full article

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6 pages, 951 KiB

Open AccessCommunication

Pyrrolizidine-Derived Alkaloids: Highly Toxic Components in the Seeds of Crotalaria cleomifolia Used in Popular Beverages in Madagascar

by Anjaramampionona Henintsoa Duvale Solofomalala, Clara Fredeline Rajemiarimoelisoa, Randriamampianina Lovarintsoa Judicael, Hanitra Ranjana Randrianarivo, Danielle Aurore Doll Rakoto, Victor Louis Jeannoda and Ahcène Boumendjel

Molecules 2021, 26(11), 3464; https://doi.org/10.3390/molecules26113464 - 7 Jun 2021

Cited by 4 | Viewed by 2307

Abstract

Seeds of Crotalaria cleomifolia (Fabaceae) are consumed in Madagascar in preparation of popular beverages. The investigation of extracts from the seeds of this species revealed the presence of high amounts of alkaloids from which two pyrrolizidine-derived alkaloids were isolated. One of them was [...] Read more.

Seeds of Crotalaria cleomifolia (Fabaceae) are consumed in Madagascar in preparation of popular beverages. The investigation of extracts from the seeds of this species revealed the presence of high amounts of alkaloids from which two pyrrolizidine-derived alkaloids were isolated. One of them was fully characterized by spectroscopic and spectrometric methods, which was found to be usaramine. Owing to the high toxicity of these alkaloids, issuing a strong warning among populations consuming the seeds of Crotalaria cleomifolia must be considered. Full article

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20 pages, 10178 KiB

Open AccessReview

Plant Occurring Flavonoids as Modulators of the Aryl Hydrocarbon Receptor

by Elizabeth Goya-Jorge, María Elisa Jorge Rodríguez, Maité Sylla-Iyarreta Veitía and Rosa M. Giner

Molecules 2021, 26(8), 2315; https://doi.org/10.3390/molecules26082315 - 16 Apr 2021

Cited by 47 | Viewed by 4667

Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR [...] Read more.

The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR ligands are recognized, with plant occurring flavonoids being the largest group of natural ligands of AhR in the human diet. The biological implications of the modulatory effects of flavonoids on AhR could be highlighted from a toxicological and environmental concern and for the possible pharmacological applicability. Overall, the possible AhR-mediated harmful and/or beneficial effects of flavonoids need to be further investigated, since in many cases they are contradictory. Similar to other AhR modulators, flavonoids commonly exhibit tissue, organ, and species-specific activities on AhR. Such cellular-context dependency could be probably beneficial in their pharmacotherapeutic use. Flavones, flavonols, flavanones, and isoflavones are the main subclasses of flavonoids reported as AhR modulators. Some of the structural features of these groups of flavonoids that could be influencing their AhR effects are herein summarized. However, limited generalizations, as well as few outright structure-activity relationships can be suggested on the AhR agonism and/or antagonism caused by flavonoids. Full article

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12 pages, 1699 KiB

Open AccessArticle

Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

by Kamel Arraki, Perle Totoson, Alain Decendit, Andy Zedet, Justine Maroilley, Alain Badoc, Céline Demougeot and Corine Girard

Molecules 2021, 26(6), 1694; https://doi.org/10.3390/molecules26061694 - 18 Mar 2021

Cited by 7 | Viewed by 2342

Abstract

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these [...] Read more.

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC₅₀ values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model. Full article

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13 pages, 7705 KiB

Open AccessArticle

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

by Reda F. A. Abdelhameed, Eman S. Habib, Ahmed K. Ibrahim, Koji Yamada, Maged S. Abdel-Kader, Safwat A. Ahmed, Amany K. Ibrahim, Jihan M. Badr and Mohamed S. Nafie

Molecules 2021, 26(4), 940; https://doi.org/10.3390/molecules26040940 - 10 Feb 2021

Cited by 13 | Viewed by 2636

Abstract

Different extracts of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, [...] Read more.

Different extracts of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, it was subjected to chromatographic separation, which resulted in the isolation of a new natural product; 7-hydroxy, 5-methoxy, methyl cinnamate (1), together with four known compounds. The structures of the pure isolated compounds were deduced based on different spectroscopic data. The new compound (1) was screened against the HepG2 and MCF-7 cells and showed IC₅₀ values of 7.43 and 10.65 µM, respectively. It induced apoptotic cell death in HepG2 with total apoptotic cell death of 58.6% (12.44-fold) compared to 4.71% in control by arresting cell cycle progression at the G1 phase. Finally, compound 1 was validated as EGFR tyrosine kinase inhibitor in both enzymatic levels (IC₅₀ = 98.65 nM compared to Erlotinib (IC₅₀ = 78.65 nM). Finally, in silico studies of compound 1 through the molecular docking indicated its high binding affinity towards EGFR protein and the ADME pharmacokinetics indicated it as a drug-like. Full article

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18 pages, 634 KiB

Open AccessReview

Colour Me Blue: The History and the Biotechnological Potential of Pyocyanin

by Thiago Gonçalves and Ulrich Vasconcelos

Molecules 2021, 26(4), 927; https://doi.org/10.3390/molecules26040927 - 10 Feb 2021

Cited by 47 | Viewed by 7001

Abstract

Pyocyanin was the first natural phenazine described. The molecule is synthesized by about 95% of the strains of Pseudomonas aeruginosa. From discovery up to now, pyocyanin has been characterised by a very rich and avant-garde history, which includes its use in antimicrobial therapy, [...] Read more.

Pyocyanin was the first natural phenazine described. The molecule is synthesized by about 95% of the strains of Pseudomonas aeruginosa. From discovery up to now, pyocyanin has been characterised by a very rich and avant-garde history, which includes its use in antimicrobial therapy, even before the discovery of penicillin opened the era of antibiotic therapy, as well as its use in electric current generation. Exhibiting an exuberant blue colour and being easy to obtain, this pigment is the subject of the present review, aiming to narrate its history as well as to unveil its mechanisms and suggest new horizons for applications in different areas of engineering, biology and biotechnology. Full article

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17 pages, 1734 KiB

Open AccessReview

Epigenetic Modifications Induced by Olive Oil and Its Phenolic Compounds: A Systematic Review

by Roberto Fabiani, Nicolò Vella and Patrizia Rosignoli

Molecules 2021, 26(2), 273; https://doi.org/10.3390/molecules26020273 - 7 Jan 2021

Cited by 22 | Viewed by 4406

Abstract

Many studies demonstrated that olive oil (especially extra virgin olive oil: EVOO) phenolic compounds are bioactive molecules with anti-cancer, anti-inflammatory, anti-aging and neuroprotective activities. These effects have been recently attributed to the ability of these compounds to induce epigenetics modifications such as miRNAs [...] Read more.

Many studies demonstrated that olive oil (especially extra virgin olive oil: EVOO) phenolic compounds are bioactive molecules with anti-cancer, anti-inflammatory, anti-aging and neuroprotective activities. These effects have been recently attributed to the ability of these compounds to induce epigenetics modifications such as miRNAs expression, DNA methylation and histone modifications. In this study, we systematically review and discuss, following the PRISMA statements, the epigenetic modifications induced by EVOO and its phenols in different experimental systems. At the end of literature search through “PubMed”, “Web of Science” and “Scopus”, 43 studies were selected.Among them, 22 studies reported data on miRNAs, 15 on DNA methylation and 13 on histone modification. Most of the “epigenomic” changes observed in response to olive oil phenols’ exposure were mechanistically associated with the cancer preventive and anti-inflammatory effects. In many cases, the epigenetics effects regarding the DNA methylation were demonstrated for olive oil but without any indication regarding the presence or not of phenols. Overall, the findings of the present systematic review may have important implications for understanding the epigenetic mechanisms behind the health effects of olive oil. However, generally no direct evidence was provided for the causal relationships between epigenetics modification and EVOO health related effects. Further studies are necessary to demonstrate the real physiological consequences of the epigenetics modification induced by EVOO and its phenolic compounds. Full article

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13 pages, 1404 KiB

Open AccessArticle

Flavonol Glycosides: In Vitro Inhibition of DPPIV, Aldose Reductase and Combating Oxidative Stress are Potential Mechanisms for Mediating the Antidiabetic Activity of Cleome droserifolia

by Amira Abdel Motaal, Heba H. Salem, Dalia Almaghaslah, Abdulrhman Alsayari, Abdullatif Bin Muhsinah, Mohammad Y. Alfaifi, Serag Eldin I. Elbehairi, Ali A. Shati and Hesham El-Askary

Molecules 2020, 25(24), 5864; https://doi.org/10.3390/molecules25245864 - 11 Dec 2020

Cited by 24 | Viewed by 2696

Abstract

Diabetes is a major health problem that is associated with high risk of various complications. Medicinal plants hold great promise against diabetes. The traditional use of Cleome droserifolia as an antidiabetic agent was correlated to its flavonol glycosides content. In the current study, [...] Read more.

Diabetes is a major health problem that is associated with high risk of various complications. Medicinal plants hold great promise against diabetes. The traditional use of Cleome droserifolia as an antidiabetic agent was correlated to its flavonol glycosides content. In the current study, five major flavonol glycosides appeared on the RP-HPLC chromatogram of the aqueous extract namely; quercetin-3-O-β-d-glucosyl-7-O-α-rhamnoside (1), isorhamnetin-7-O-β-neohesperidoside (2), isorhamnetin-3-O-β-d-glucoside (3) kaempferol-4′-methoxy-3,7-O-α-dirhamnoside (4), and isorhamnetin-3-O-α-(4″-acetylrhamnoside)-7-O-α-rhamnoside (5). The inhibitory activities of these compounds were tested in vitro against several enzymes involved in diabetes management. Only the relatively less polar methoxylated flavonol glycosides (4, 5) showed mild to moderate α-amylase and α-glucosidase inhibitory activities. Compounds 1–4 displayed remarkable inhibition of dipeptidyl peptidase IV (DPPIV) enzyme (IC₅₀ 0.194 ± 0.06, 0.573 ± 0.03, 0.345 ± 0.02 and 0.281 ± 0.05 µg/mL, respectively) comparable to vildagliptin (IC₅₀ 0.154 ± 0.02 µg/mL). Moreover, these compounds showed high potential in preventing diabetes complications through inhibiting aldose reductase enzyme and combating oxidative stress. Both isorhamnetin glycoside derivatives (2, 3) exhibited the highest activities in aldose reductase inhibition and compound 2 (IC₅₀ 5.45 ± 0.26 µg/mL) was even more potent than standard quercetin (IC₅₀ 7.77 ± 0.43 µg/mL). Additionally, these flavonols exerted excellent antioxidant capacities through 2, 2-diphenyl-1-picrylhydrazil (DPPH) and ferric reducing antioxidant (FRAP) assays. Full article

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32 pages, 2428 KiB

Open AccessReview

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

by Catarina Serafim, Maria Elaine Araruna, Edvaldo Alves Júnior, Margareth Diniz, Clélia Hiruma-Lima and Leônia Batista

Molecules 2020, 25(22), 5431; https://doi.org/10.3390/molecules25225431 - 20 Nov 2020

Cited by 61 | Viewed by 16327

Abstract

Peptic ulcers are characterized by erosions on the mucosa of the gastrointestinal tract that may reach the muscle layer. Their etiology is multifactorial and occurs when the balance between offensive and protective factors of the mucosa is disturbed. Peptic ulcers represent a global [...] Read more.

Peptic ulcers are characterized by erosions on the mucosa of the gastrointestinal tract that may reach the muscle layer. Their etiology is multifactorial and occurs when the balance between offensive and protective factors of the mucosa is disturbed. Peptic ulcers represent a global health problem, affecting millions of people worldwide and showing high rates of recurrence. Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important predisposing factors for the development of peptic ulcers. Therefore, new approaches to complementary treatments are needed to prevent the development of ulcers and their recurrence. Natural products such as medicinal plants and their isolated compounds have been widely used in experimental models of peptic ulcers. Flavonoids are among the molecules of greatest interest in biological assays due to their anti-inflammatory and antioxidant properties. The present study is a literature review of flavonoids that have been reported to show peptic ulcer activity in experimental models. Studies published from January 2010 to January 2020 were selected from reference databases. This review refers to a collection of flavonoids with antiulcer activity in vivo and in vitro models. Full article

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14 pages, 2566 KiB

Open AccessArticle

Novel Therapeutic Effects of Pterosin B on Ang II-Induced Cardiomyocyte Hypertrophy

by Chang Youn Lee, Han Ki Park, Bok-Sim Lee, Seongtae Jeong, Sung-Ae Hyun, Jung-Won Choi, Sang Woo Kim, Seahyoung Lee, Soyeon Lim and Ki-Chul Hwang

Molecules 2020, 25(22), 5279; https://doi.org/10.3390/molecules25225279 - 12 Nov 2020

Cited by 15 | Viewed by 3495

Abstract

Pathological cardiac hypertrophy is characterized by an abnormal increase in cardiac muscle mass in the left ventricle, resulting in cardiac dysfunction. Although various therapeutic approaches are being continuously developed for heart failure, several studies have suggested natural compounds as novel potential strategies. Considering [...] Read more.

Pathological cardiac hypertrophy is characterized by an abnormal increase in cardiac muscle mass in the left ventricle, resulting in cardiac dysfunction. Although various therapeutic approaches are being continuously developed for heart failure, several studies have suggested natural compounds as novel potential strategies. Considering relevant compounds, we investigated a new role for Pterosin B for which the potential life-affecting biological and therapeutic effects on cardiomyocyte hypertrophy are not fully known. Thus, we investigated whether Pterosin B can regulate cardiomyocyte hypertrophy induced by angiotensin II (Ang II) using H9c2 cells. The antihypertrophic effect of Pterosin B was evaluated, and the results showed that it reduced hypertrophy-related gene expression, cell size, and protein synthesis. In addition, upon Ang II stimulation, Pterosin B attenuated the activation and expression of major receptors, Ang II type 1 receptor and a receptor for advanced glycation end products, by inhibiting the phosphorylation of PKC-ERK-NF-κB pathway signaling molecules. In addition, Pterosin B showed the ability to reduce excessive intracellular reactive oxygen species, critical mediators for cardiac hypertrophy upon Ang II exposure, by regulating the expression levels of NAD(P)H oxidase 2/4. Our results demonstrate the protective role of Pterosin B in cardiomyocyte hypertrophy, suggesting it is a potential therapeutic candidate. Full article

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11 pages, 1323 KiB

Open AccessArticle

Chemical Constituent of β-Glucuronidase Inhibitors from the Root of Neolitsea acuminatissima

by Chu-Hung Lin, Hsiao-Jung Chou, Chih-Chi Chang, Ih-Sheng Chen, Hsun-Shuo Chang, Tian-Lu Cheng, Yueh-Hsiung Kuo and Horng-Huey Ko

Molecules 2020, 25(21), 5170; https://doi.org/10.3390/molecules25215170 - 6 Nov 2020

Cited by 5 | Viewed by 2335

Abstract

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4–15) were isolated [...] Read more.

Neolitsea acuminatissima (Lauraceae) is an endemic plant in Taiwan. One new carboline alkaloid, demethoxydaibucarboline A (1), two new eudesmanolide-type sesquiterpenes, methyl-neolitacumone A (2), neolitacumone E (3), and twelve known compounds (4–15) were isolated from the root of Neolitsea acuminatissima. Their structures were elucidated by spectroscopic analysis. Glucuronidation represents a major metabolism process of detoxification for carcinogens in the liver. However, intestinal bacterial β-Glucuronidase (βG) has been considered pivotal to colorectal carcinogenesis. To develop specific bacterial-βG inhibitors with no effect on human βG, methanolic extract of roots of N. acuminatissima was selected to evaluate their anti-βG activity. Among the isolates, demethoxydaibucarboline A (1) and quercetin (8) showed a strong bacterial βG inhibitory effect with an inhibition ratio of about 80%. Methylneolitacumone A (2) and epicatechin (10) exhibited a moderate or weak inhibitory effect and the enzyme activity was less than 45% and 74%, respectively. These four compounds specifically inhibit bacterial βG but not human βG. Thus, they are expected to be used for the purpose of reducing chemotherapy-induced diarrhea (CID). The results suggest that the constituents of N. acuminatissima have the potential to be used as CID relief candidates. However, further investigation is required to determine their mechanisms of action. Full article

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17 pages, 793 KiB

Open AccessArticle

Biological Potential of Fruit and Leaves of Strawberry Tree (Arbutus unedo L.) from Croatia

by Jana Šic Žlabur, Sandro Bogdanović, Sandra Voća and Martina Skendrović Babojelić

Molecules 2020, 25(21), 5102; https://doi.org/10.3390/molecules25215102 - 3 Nov 2020

Cited by 20 | Viewed by 3746

Abstract

The strawberry tree fruit and leaf are a rich source of minerals, easily digestible sugars, dietary fibers, vitamins (especially vitamin C) and many bioactive compounds of significant functional value. Due to their favorable chemical composition, fruits have recently become increasingly popular in consumption. [...] Read more.

The strawberry tree fruit and leaf are a rich source of minerals, easily digestible sugars, dietary fibers, vitamins (especially vitamin C) and many bioactive compounds of significant functional value. Due to their favorable chemical composition, fruits have recently become increasingly popular in consumption. The aim of this study was to determine the physical-chemical composition, content of bioactive compounds, and also the antioxidant capacity of the fruit and leaves of wild strawberry tree populations among the Adriatic coast in Croatia, as well as to investigate the influence of location on the content of specific bioactive compounds. According to the obtained results, both fruit and leaves are pronouncedly high in vitamin C content, the average value for fruits amounted to 224.21 mg/100 g FW, while that for leaves amounted to 138.08 mg/100 g FW. Additionally, significantly high values of total polyphenolic compounds were recorded both in fruits (average value of 637.94 mg GAE/100 g FW) and especially in leaves (average value of 2157.01 mg GAE/100 g FW). Several pigments from different categories were determined in the fruit depending on fruit maturity, including: total anthocyanins, β-carotene and lycopene; while in leaves chlorophylls and carotenoids. Given the high content of different bioactive compounds high values of antioxidant capacity were determined (the average value for fruits was 2269.96 µmol TE/kg and for leaves, 2237.16 µmol TE/kg). Location strongly influenced the physical-chemical composition and also the content of specialized metabolites; populations collected from southern areas (central and south Dalmatia) of the Adriatic coast tended to have higher amounts of vitamin C, total phenols, total anthocyanins and β-carotene. Full article

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11 pages, 2605 KiB

Open AccessArticle

Evaluation of Anti-Mycobacterial Compounds in a Silkworm Infection Model with Mycobacteroides abscessus

by Kanji Hosoda, Nobuhiro Koyama, Hiroshi Hamamoto, Akiho Yagi, Ryuji Uchida, Akihiko Kanamoto and Hiroshi Tomoda

Molecules 2020, 25(21), 4971; https://doi.org/10.3390/molecules25214971 - 27 Oct 2020

Cited by 17 | Viewed by 2713

Abstract

Among four mycobacteria, Mycobacterium avium, M. intracellulare, M. bovis BCG and Mycobacteroides (My.) abscessus, we established a silkworm infection assay with My. abscessus. When silkworms (fifth-instar larvae, n = 5) were infected through the hemolymph with My. [...] Read more.

Among four mycobacteria, Mycobacterium avium, M. intracellulare, M. bovis BCG and Mycobacteroides (My.) abscessus, we established a silkworm infection assay with My. abscessus. When silkworms (fifth-instar larvae, n = 5) were infected through the hemolymph with My. abscessus (7.5 × 10⁷ CFU/larva) and bred at 37 °C, they all died around 40 h after injection. Under the conditions, clarithromycin and amikacin, clinically used antimicrobial agents, exhibited therapeutic effects in a dose-dependent manner. Furthermore, five kinds of microbial compounds, lariatin A, nosiheptide, ohmyungsamycins A and B, quinomycin and steffimycin, screened in an in vitro assay to observe anti-My. abscessus activity from 400 microbial products were evaluated in this silkworm infection assay. Lariatin A and nosiheptide exhibited therapeutic efficacy. The silkworm infection model with My. abscessus is useful to screen for therapeutically effective anti-My. abscessus antibiotics. Full article

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9 pages, 400 KiB

Open AccessCommunication

A New Thiopeptide Antibiotic, Micrococcin P3, from a Marine-Derived Strain of the Bacterium Bacillus stratosphericus

by Weihong Wang, Kyu-Hyung Park, Jusung Lee, Eunseok Oh, Chanyoon Park, Eunmo Kang, Juni Lee and Heonjoong Kang

Molecules 2020, 25(19), 4383; https://doi.org/10.3390/molecules25194383 - 24 Sep 2020

Cited by 11 | Viewed by 3302

Abstract

A new thiopeptide (micrococcin P3, 1) and a known one (micrococcin P1, 2) were isolated from the culture broth of a marine-derived strain of Bacillus stratosphericus. The structures of both compounds were elucidated using spectroscopic methods, including extensive 1D and [...] Read more.

A new thiopeptide (micrococcin P3, 1) and a known one (micrococcin P1, 2) were isolated from the culture broth of a marine-derived strain of Bacillus stratosphericus. The structures of both compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR analysis, high resolution mass spectrometry (HRMS), and tandem mass spectrometry. Both compounds exhibited potent antibacterial activities against Gram-positive strains with minimum inhibitory concentration (MIC) values of 0.05−0.8 μg/mL and did not show cytotoxicity in the MTT assay up to a concentration of 10 μM. This study adds a new promising member, micrococcin P3, to the family of thiopeptide antibiotics, which shows potential for the development of new antibiotics targeting Gram-positive bacteria. Full article

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18 pages, 2710 KiB

Open AccessReview

Thymol and Thyme Essential Oil—New Insights into Selected Therapeutic Applications

by Adam Kowalczyk, Martyna Przychodna, Sylwia Sopata, Agnieszka Bodalska and Izabela Fecka

Molecules 2020, 25(18), 4125; https://doi.org/10.3390/molecules25184125 - 9 Sep 2020

Cited by 239 | Viewed by 29741

Abstract

Thymol (2-isopropyl-5-methylphenol) belongs to the phenolic monoterpenes and mostly occurs in thyme species. It is one of the main compounds of thyme essential oil. Both thymol and thyme essential oil have long been used in traditional medicine as expectorant, anti-inflammatory, antiviral, antibacterial, and [...] Read more.

Thymol (2-isopropyl-5-methylphenol) belongs to the phenolic monoterpenes and mostly occurs in thyme species. It is one of the main compounds of thyme essential oil. Both thymol and thyme essential oil have long been used in traditional medicine as expectorant, anti-inflammatory, antiviral, antibacterial, and antiseptic agents, mainly in the treatment of the upper respiratory system. The current search for new directions of biological or therapeutic activities of natural plant substances with known structures includes thyme essential oil and thymol. Novel studies have demonstrated their antibiofilm, antifungal, antileishmanial, antiviral, and anticancer properties. Also, their new therapeutic formulations, such as nanocapsules containing these constituents, can be beneficial in medicinal practice and create opportunities for their extensive use. Extensive application of thymol and thyme essential oil in the healthcare sector is very promising but requires further research and analysis. Full article

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29 pages, 3117 KiB

Open AccessReview

Encapsulation of Lipid-Soluble Bioactives by Nanoemulsions

by Shahin Banasaz, Ksenia Morozova, Giovanna Ferrentino and Matteo Scampicchio

Molecules 2020, 25(17), 3966; https://doi.org/10.3390/molecules25173966 - 31 Aug 2020

Cited by 49 | Viewed by 6400

Abstract

Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for oxidation. Lipid-soluble bioactives, such as vitamins A, E, D and K, carotenoids, polyunsaturated fatty acids (PUFA) and essential oils are [...] Read more.

Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for oxidation. Lipid-soluble bioactives, such as vitamins A, E, D and K, carotenoids, polyunsaturated fatty acids (PUFA) and essential oils are generally dispersed in water-based solutions by homogenization. Among the different homogenization technologies available, nanoemulsions are one of the most promising. Accordingly, this review aims to summarize the most recent advances in nanoemulsion technology for the encapsulation of lipid-soluble bioactives. Modern approaches for producing nanoemulsion systems will be discussed. In addition, the challenges on the encapsulation of common food ingredients, including the physical and chemical stability of the nanoemulsion systems, will be also critically examined. Full article

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9 pages, 852 KiB

Open AccessArticle

In Vitro Scolicidal Activity of the Sesquiterpenes Isofuranodiene, α-Bisabolol and Farnesol on Echinococcus granulosus Protoscoleces

by Mohammad Reza Youssefi, Ali Nikpay, Niloufar Hassanpour, Aida Mirzapour, Parisa Saleh Tabari, Roman Pavela, Filippo Maggi and Riccardo Petrelli

Molecules 2020, 25(16), 3593; https://doi.org/10.3390/molecules25163593 - 7 Aug 2020

Cited by 13 | Viewed by 3243

Abstract

Cystic echinococcosis (CE) remains an important challenge both in humans and animals. There is no safe and suitable remedy for CE, so the discovery of new compounds with promising scolicidal effects, particularly from herbal sources, is of great importance for therapeutic uses in [...] Read more.

Cystic echinococcosis (CE) remains an important challenge both in humans and animals. There is no safe and suitable remedy for CE, so the discovery of new compounds with promising scolicidal effects, particularly from herbal sources, is of great importance for therapeutic uses in the treatment and prevention of CE reappearance. Sesquiterpenes are C15 organic compounds made up of three isoprene units and mostly occurring as fragrant components of essential oils. They are of economic importance for the cosmetic and pharmaceutical industry, and recently attracted the attention of the scientific community for their remarkable parasiticidal properties. In the present study, we have focused on three known sesquiterpenes, isofuranodiene (IFD), α-bisabolol (BSB), and farnesol (FOH), as important phytoconstituents of the essential oils of wild celery (Smyrnium olusatrum), chamomile (Matricaria chamomilla), and acacia farnese (Vachellia farnesiana), respectively. Protoscoleces were recovered from fertile hydatid cysts and were exposed to different concentrations of the three tested compounds for different exposure times. The viability of protoscoleces was confirmed by 0.1% eosin staining. Results of scolicidal activity evaluations showed that IFD possessed the best effect against Echinococcus granulosus protoscoleces (LC₅₀ and LC₉₀ values of 8.87 and 25.48 µg/mL, respectively), followed by BSB (LC₅₀ of 103.2 µg/mL) and FOH (LC₅₀ of 113.68 µg/mL). The overall toxicity of IFD differed significantly from those of FOH and BSB, while there was no significant difference in toxicity between the latter compounds (p > 0.05). The present study showed that IFD seems to be a promising scolicidal agent and can be further tested to become a candidate for CE treatment. Full article

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14 pages, 464 KiB

Open AccessArticle

Mineral Composition of Three Popular Wild Mushrooms from Poland

by Michalina Gałgowska and Renata Pietrzak-Fiećko

Molecules 2020, 25(16), 3588; https://doi.org/10.3390/molecules25163588 - 6 Aug 2020

Cited by 16 | Viewed by 3682

Abstract

The region of Warmia and Mazury is characterized by the special diversity and richness of its natural environment, including large forest complexes, where wild mushrooms are commonly collected and consumed. This study aimed to examine the differences in mineral content (calcium, magnesium, sodium, [...] Read more.

The region of Warmia and Mazury is characterized by the special diversity and richness of its natural environment, including large forest complexes, where wild mushrooms are commonly collected and consumed. This study aimed to examine the differences in mineral content (calcium, magnesium, sodium, potassium, iron, zinc, copper, manganese) of three species of mushrooms collected in north-eastern Poland. The research material consisted of dried samples of king bolete (Boletus edulis), bay bolete (Boletus badius), and chanterelle (Cantharellus cibarius) collected in the region of Warmia and Mazury. The content of the above-mentioned elements in mushroom fruit bodies was determined using the flame atomic absorption spectrometry (acetylene-air flame) and the emission technique (acetylene-air flame) for sodium and potassium. For the majority of micro- and macroelements, the studies confirmed the presence of significant differences in their content, depending on the species of fungi. The studied mushrooms cover a significant percentage of daily demand for many of the minerals. This concerns mainly copper, zinc, and potassium, although none of the species was a good source of calcium and sodium. Among the analyzed mushrooms, chanterelle is the best source of most minerals. Full article

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14 pages, 1116 KiB

Open AccessArticle

Recovery of Anthocyanins from Passion Fruit Epicarp for Food Colorants: Extraction Process Optimization and Evaluation of Bioactive Properties

by Bejaoui Ghada, Eliana Pereira, José Pinela, Miguel A. Prieto, Carla Pereira, Ricardo C. Calhelha, Dejan Stojković, Marina Sokóvić, Khalil Zaghdoudi, Lillian Barros and Isabel C. F. R. Ferreira

Molecules 2020, 25(14), 3203; https://doi.org/10.3390/molecules25143203 - 14 Jul 2020

Cited by 28 | Viewed by 5139

Abstract

The potential of passion fruit (Passiflora edulis Sims) epicarp to produce anthocyanin-based colorants with bioactive properties was evaluated. First, a five-level three-factor factorial design coupled with response surface methodology was implemented to optimize the extraction of anthocyanins from dark purple epicarps. The [...] Read more.

The potential of passion fruit (Passiflora edulis Sims) epicarp to produce anthocyanin-based colorants with bioactive properties was evaluated. First, a five-level three-factor factorial design coupled with response surface methodology was implemented to optimize the extraction of anthocyanins from dark purple epicarps. The extraction yield and cyanidin-3-O-glucoside content were used as response criteria. The constructed models were fitted to the experimental data and used to calculate the optimal processing conditions (t = 38 min, T = 20 °C, S = 0% ethanol/water (v/v) acidified with citric acid to pH 3, and R_S/L = 50 g/L) that lead to maximum responses (3.4 mg/g dried epicarp and 9 mg/g extract). Then, the antioxidant, antimicrobial, and cytotoxic activities of anthocyanin extracts obtained using the optimized method and a conventional extraction method were evaluated in vitro. The extract obtained by the optimized method revealed a higher bioactivity, in agreement with the higher cyanidin-3-O-glucoside content. This study highlighted the coloring and bioactive potential of a bio-based ingredient recycled from a bio-waste, which promotes a sustainable bioeconomy in the agri-food sector. Full article

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16 pages, 3249 KiB

Open AccessArticle

Characterization, Classification and Authentication of Turmeric and Curry Samples by Targeted LC-HRMS Polyphenolic and Curcuminoid Profiling and Chemometrics

by Nerea Núñez, Oscar Vidal-Casanella, Sonia Sentellas, Javier Saurina and Oscar Núñez

Molecules 2020, 25(12), 2942; https://doi.org/10.3390/molecules25122942 - 26 Jun 2020

Cited by 19 | Viewed by 4610

Abstract

The importance of monitoring bioactive substances as food features to address sample classification and authentication is increasing. In this work, targeted liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) polyphenolic and curcuminoid profiles were evaluated as chemical descriptors to deal with the characterization [...] Read more.

The importance of monitoring bioactive substances as food features to address sample classification and authentication is increasing. In this work, targeted liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) polyphenolic and curcuminoid profiles were evaluated as chemical descriptors to deal with the characterization and classification of turmeric and curry samples. The profiles corresponding to bioactive substances were obtained by TraceFinder^TM software using accurate mass databases with 53 and 24 polyphenolic and curcuminoid related compounds, respectively. For that purpose, 21 turmeric and 9 curry samples commercially available were analyzed in triplicate by a simple liquid–solid extraction procedure using dimethyl sulfoxide as extracting solvent. The obtained results demonstrate that the proposed profiles were excellent chemical descriptors for sample characterization and classification by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), achieving 100% classification rates. Curcuminoids and some specific phenolic acids such as trans-cinnamic, ferulic and sinapic acids, helped on the discrimination of turmeric samples; polyphenols, in general, were responsible for the curry sample distinction. Besides, the combination of both polyphenolic and curcuminoid profiles was necessary for the simultaneous characterization and classification of turmeric and curry samples. Discrimination among turmeric species such as Curcuma longa vs. Curcuma zedoaria, as well as among different Curcuma longa varieties (Alleppey, Madras and Erode) was also accomplished. Full article

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11 pages, 464 KiB

Open AccessArticle

Influence of Drying Method on Some Bioactive Compounds and the Composition of Volatile Components in Dried Pink Rock Rose (Cistus creticus L.)

by Natalia Matłok, Sabina Lachowicz, Józef Gorzelany and Maciej Balawejder

Molecules 2020, 25(11), 2596; https://doi.org/10.3390/molecules25112596 - 3 Jun 2020

Cited by 16 | Viewed by 3611

Abstract

This study investigates the effects of various drying methods applied to leaves of Cistus creticus L. on the contents of polyphenols and the composition of the volatile fraction. The following four drying methods were used: convection drying at a temperature of 40 °C [...] Read more.

This study investigates the effects of various drying methods applied to leaves of Cistus creticus L. on the contents of polyphenols and the composition of the volatile fraction. The following four drying methods were used: convection drying at a temperature of 40 °C (CD 40 °C), 50 °C (CD 50 °C), and 60 °C (CD 60 °C); vacuum-microwave (VMD 240 W); combined drying, involving convection pre-drying (50 °C) and vacuum-microwave (240 W) finish drying (CPD-VMFD) as well as freeze-drying (FD). Polyphenols in the dried leaves were determined using chromatography-photodiode detector-quadrupole/time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS). The contents of odoriferous substances in the dry material were determined by means of head space-solid phase microextraction (HS-SPME) with the use of a gas chromatograph (GC). Thirty-seven polyphenol components including 21 flavonols, eight flavan-3-ols, and eight hydrolyzed tannins in dry Pink Rock Rose material were found for the first time. The highest contents of polyphenols, totaling 2.8 g 100 g⁻¹ dry matter (d.m.), were found in the samples subjected to the CPD/VMFD drying method. Pink Rock Rose subjected to this drying method was characterized by large quantities of odoriferous compounds, mainly eugenol, thymol, and carvacrol, which contribute to its antiseptic properties. By using CPD/VMFD methods, it is possible to obtain fine quality dry material from the leaves of C. creticus. Full article

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9 pages, 1736 KiB

Open AccessArticle

Bioactivity-Guided Identification of Anti-Adipogenic Isothiocyanates in the Moringa (Moringa oleifera) Seed and Investigation of the Structure-Activity Relationship

by Linhua Huang, Chunmao Yuan and Yu Wang

Molecules 2020, 25(11), 2504; https://doi.org/10.3390/molecules25112504 - 28 May 2020

Cited by 12 | Viewed by 3658

Abstract

Due to the side effects of obesity medications, many studies have focused on the natural products used in the daily diet to control weight. Moringa seed pods and leaves are widely used as vegetables or diet supplements due to the high nutrition value. [...] Read more.

Due to the side effects of obesity medications, many studies have focused on the natural products used in the daily diet to control weight. Moringa seed pods and leaves are widely used as vegetables or diet supplements due to the high nutrition value. However, no bioactivity-guided anti-adipogenic study was previously conducted. Therefore, a preadipocyte cell line was adopted as the bioactivity assay to identify the anti-adipogenic compounds in the peeled Moringa seed. Two known sulphur-containing compounds (1 and 2) were isolated and identified. Compound 2, 4-(α-l-rhamnosyloxy) benzyl isothiocyanate, showed a great anti-adipogneic effect with an IC₅₀ value of 9.2 μg/mL. The isothiocyanate (ITC) group in compound 2 could be responsible for the inhibitory activity. In addition, a series of compounds with the ITC group were used to further investigate the structure-activity relationship, indicating foods containing ITC derivatives have the potential of being used to control weight. Full article

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17 pages, 2839 KiB

Open AccessArticle

Anti-Acne Action of Peptides Isolated from Burdock Root—Preliminary Studies and Pilot Testing

by Malgorzata Miazga-Karska, Katarzyna Michalak and Grazyna Ginalska

Molecules 2020, 25(9), 2027; https://doi.org/10.3390/molecules25092027 - 27 Apr 2020

Cited by 20 | Viewed by 7154

Abstract

This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW [...] Read more.

This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW peptides fraction of this plant. Br-p were isolated using gel filtration and a 10 kDa cut-off membrane. The obtained peptides were identified by MALDI TOF/TOF. Antibacterial activity was tested against acne strains using diffusion tests, MIC and MBC. The fibroblast cytotoxicity of Br-p was tested, and the selectivity index (SI) value was determined. The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. One of the Br-p peptides assessed on MALDI RapidDeNovo was LRCDYGRFFASKSLYDPLKKRR cationic peptide. It was analogous to that contained in A. lappa protein, and theoretically it was matched as a peptide with antibiotic nature. Br-p did not show toxicity to fibroblasts in the tested concentration up to 10 mg/mL, obtaining CC₅₀ 10 mg/mL. The SI value for the tested Propionibacterium strains ranged from 160 to 320. Finally, an active dressing based on chitosan/alginate/genipin was prepared using freeze-drying. The formed dressing was evaluated for its anti-acne activity. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin. Full article

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15 pages, 694 KiB

Open AccessArticle

Profiling of Individual Desulfo-Glucosinolate Content in Cabbage Head (Brassica oleracea var. capitata) Germplasm

by Shiva Ram Bhandari, Juhee Rhee, Chang Sun Choi, Jung Su Jo, Yu Kyeong Shin and Jun Gu Lee

Molecules 2020, 25(8), 1860; https://doi.org/10.3390/molecules25081860 - 17 Apr 2020

Cited by 26 | Viewed by 4119

Abstract

Individual glucosinolates (GSLs) were assessed to select cabbage genotypes for a potential breeding program. One hundred forty-six cabbage genotypes from different origins were grown in an open field from March to June 2019; the cabbage heads were used for GSL analyses. Seven aliphatics [...] Read more.

Individual glucosinolates (GSLs) were assessed to select cabbage genotypes for a potential breeding program. One hundred forty-six cabbage genotypes from different origins were grown in an open field from March to June 2019; the cabbage heads were used for GSL analyses. Seven aliphatics [glucoiberin (GIB), progoitrin (PRO), epi-progoitrin (EPI), sinigrin (SIN), glucoraphanin (GRA), glucoerucin (GER) and gluconapin (GNA)], one aromatic [gluconasturtiin (GNS)] and four indolyl GSLs [glucobrassicin (GBS), 4-hydroxyglucobrassicin (4HGBS), 4-methoxyglucobrassicin (4MGBS), neoglucobrassicin (NGBS)] were found this study. Significant variation was observed in the individual GSL content and in each class of GSLs among the cabbage genotypes. Aliphatic GSLs were predominant (58.5%) among the total GSLs, followed by indolyl GSL (40.7%) and aromatic GSLs (0.8%), showing 46.4, 51.2 and 137.8% coefficients of variation, respectively. GIB, GBS and NGBS were the most common GSLs found in all genotypes. GBS was the most dominant GSL, with an average value of 3.91 µmol g⁻¹ (0.79 to 13.14 µmol g⁻¹). SIN, GIB, PRO and GRA were the other major GSLs, showing average values of 3.45, 1.50, 0.77 and 0.62 µmol g⁻¹, respectively. The genotypes with relatively high contents of GBS, SIN, GIB and GRA warrant detailed studies for future breeding programs since the hydrolysis products of these GSLs have several anti-cancer properties. Full article

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13 pages, 2983 KiB

Open AccessArticle

The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet

by Shichen Pu, Yumin Liu, Shan Liang, Pin Liu, Hongmei Qian, Qian Wu and Yuliang Wang

Molecules 2020, 25(6), 1392; https://doi.org/10.3390/molecules25061392 - 18 Mar 2020

Cited by 6 | Viewed by 3038

Abstract

Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in [...] Read more.

Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in hamsters and analyzed the metabolic changes using gas chromatography time-of-flight mass spectrometry (GC/TOF MS). Compared with the model group, a variety of different metabolites of artesunate and ursolic acid, alone or in combination, were found and confirmed. These differential metabolites, including fatty acids, lipids, and amino acids, were involved in lipid metabolism, energy metabolism, and amino acid metabolism. It indicated that two agents of artesunate and ursolic acid could attenuate or normalize the metabolic transformation on these metabolic pathways. Full article

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14 pages, 2411 KiB

Open AccessArticle

Anti-Adipogenic and Anti-Inflammatory Activities of (−)-epi-Osmundalactone and Angiopteroside from Angiopteris helferiana C.Presl

by Ramakanta Lamichhane, Prakash Raj Pandeya, Kyung-Hee Lee, Se-Gun Kim, Hari Prasad Devkota and Hyun-Ju Jung

Molecules 2020, 25(6), 1337; https://doi.org/10.3390/molecules25061337 - 15 Mar 2020

Cited by 13 | Viewed by 3943

Abstract

Angiopteris helferiana C.Presl is a gigantic fleshy-type fern, belonging to Marattiaceae family. In previous study, we reported the potent anti-adipogenic and anti-inflammatory activities of ethylacetate (EtOAc) and n-butanol (BuOH) fractions of methanol extract of rhizomes of A. helferiana. In continuation, in [...] Read more.

Angiopteris helferiana C.Presl is a gigantic fleshy-type fern, belonging to Marattiaceae family. In previous study, we reported the potent anti-adipogenic and anti-inflammatory activities of ethylacetate (EtOAc) and n-butanol (BuOH) fractions of methanol extract of rhizomes of A. helferiana. In continuation, in this study, we report the isolation, characterization, and bioactivity analysis of principle bioactive compounds in these fractions. (−)-epi-Osmundalactone (1) and angiopteroside (2) were isolated from EtOAc and BuOH fractions, respectively. The structures of these compounds were established on the basis of NMR spectroscopic data. The quantification study using UPLC revealed the contents of compounds 1 and 2 in the dried rhizome to be 1.54% and 3.2%, respectively. These compounds were evaluated for their anti-adipogenic and anti-inflammatory activities using 3T3-L1 and RAW 264.7 cells, respectively. Compound 1 (2.5 µg/mL) and 2 (20 µg/mL) inhibited the lipid production by 35% and 25%, respectively. Regarding the anti-inflammatory activity, compound 1 (5 µg/mL) inhibited the nitrite production by nearly 82%. In conclusion, the presence of potent anti-adipogenic and anti-inflammatory compounds in A. helferiana indicate its potential role in the use of herb-based treatment for obesity and other related diseases. Full article

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15 pages, 3962 KiB

Open AccessArticle

The Protective Effect of the Polysaccharide Precursor, D-Isofloridoside, from Laurencia undulata on Alcohol-Induced Hepatotoxicity in HepG2 Cells

by Shengtao Yang, Mei-Fang Chen, Bomi Ryu, Jiali Chen, Zhenbang Xiao, Pengzhi Hong, Shengli Sun, Di Wang, Zhong-Ji Qian and Chunxia Zhou

Molecules 2020, 25(5), 1024; https://doi.org/10.3390/molecules25051024 - 25 Feb 2020

Cited by 11 | Viewed by 3579

Abstract

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that [...] Read more.

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods. Full article

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13 pages, 2374 KiB

Open AccessArticle

Isolation of Unstable Isomers of Lucilactaene and Evaluation of Anti-Inflammatory Activity of Secondary Metabolites Produced by the Endophytic Fungus Fusarium sp. QF001 from the Roots of Scutellaria baicalensis

by Sailesh Maharjan, Sang Bong Lee, Geum Jin Kim, Sung Jin Cho, Joo-Won Nam, Jungwook Chin and Hyukjae Choi

Molecules 2020, 25(4), 923; https://doi.org/10.3390/molecules25040923 - 19 Feb 2020

Cited by 14 | Viewed by 4336

Abstract

The filamentous fungal pathogen Fusarium sp. causes several crop diseases. Some Fusarium sp. are endophytes that produce diverse valuable bioactive secondary metabolites. Here, extensive chemical investigation of the endophytic fungus, Fusarium sp. QF001, isolated from the inner rotten part of old roots of [...] Read more.

The filamentous fungal pathogen Fusarium sp. causes several crop diseases. Some Fusarium sp. are endophytes that produce diverse valuable bioactive secondary metabolites. Here, extensive chemical investigation of the endophytic fungus, Fusarium sp. QF001, isolated from the inner rotten part of old roots of Scutellariae baicalensis resulted in the isolation of two new photosensitive geometrical isomers of lucilactaene (compounds 2 and 3) along with lucilactaene (6) and six other known compounds (fusarubin (1), (+)-solaniol (4), javanicin (5), 9-desmethylherbarine (7), NG391 (8) and NG393 (9)). Newly isolated isomers and lucilactaene were unstable under light at room temperature and tended to be a mixture in equilibrium state when exposed to a polar protic solvent during reversed phase chromatography. Normal phase chromatography under dim light conditions with an aprotic mobile phase led to the successful isolation of the relatively unstable isomers 2 and 3. Their structures were elucidated as 8(Z)-lucilactaene (2) and 4(Z)-lucilactaene (3) based on spectroscopic data. The absolute configuration of 4 was speculated to be R by computer-assisted specific rotation analysis. The isolated compounds could inhibit NO production and suppress pro-inflammatory cytokines expression in LPS-stimulated macrophage cells. These properties of the isolated compounds indicate their potential use as anti-inflammatory drugs. Full article

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20 pages, 2069 KiB

Open AccessReview

A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders

by Mariangela Marrelli, Giancarlo Statti and Filomena Conforti

Molecules 2020, 25(3), 649; https://doi.org/10.3390/molecules25030649 - 3 Feb 2020

Cited by 44 | Viewed by 5930

Abstract

Wild foods constitute an essential component of people’s diets around the world. According to the Food and Agriculture Organization (FAO), over 100 million people in the EU consume wild foods, while 65 million collect some form of wild food themselves. The Mediterranean basin [...] Read more.

Wild foods constitute an essential component of people’s diets around the world. According to the Food and Agriculture Organization (FAO), over 100 million people in the EU consume wild foods, while 65 million collect some form of wild food themselves. The Mediterranean basin is a biodiversity hotspot of wild edible species. Nowadays, due to the renewed interest in alimurgic plants and the recent findings on the beneficial role of their phytochemical constituents, these species have been defined as “new functional foods”. Research on natural products has recently regained importance with the growing understanding of their biological significance. Botanical food supplements marketed for weight and fat loss in obese subjects will be one of the most important items in marketed nutraceuticals. The aim of this report was to review the phytochemical compounds of Mediterranean wild edible species and their therapeutic potential against obesity and its related disorders. Results on the in vitro and in vivo activity of the most interesting plant extracts and their bioactive components are presented and discussed. The most interesting discoveries on their mechanisms of action are reported as well. Overall, this contribution highlights the importance and beneficial health roles of wild edible species. Full article

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9 pages, 1246 KiB

Open AccessArticle

Naphthoquinone Derivatives with Anti-Inflammatory Activity from Mangrove-Derived Endophytic Fungus Talaromyces sp. SK-S009

by Hongju Liu, Chong Yan, Changqun Li, Tingting You and Zhigang She

Molecules 2020, 25(3), 576; https://doi.org/10.3390/molecules25030576 - 29 Jan 2020

Cited by 37 | Viewed by 3690

Abstract

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3–12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis [...] Read more.

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3–12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis of the nuclear magnetic resonance (NMR), mass spectrometry (MS) and circular dichroism (CD), as well as by comparison with literature data. These compounds significantly inhibited the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophage cell line (RAW 264.7 cells). The half maximal inhibitory concentration (IC₅₀) values, except for compound 2, were lower than that of indomethacin (26.3 μM). Compound 9 inhibited the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in RAW 264.7 macrophages. Additionally, compound 9 reduced the mRNA levels of pro-inflammatory factors interleukin (IL)1β, IL-6, and tumor necrosis factor (TNF)-α. The results of this study demonstrated that these 1, 4-naphthoquinone derivatives can inhibit LPS-induced inflammation. Full article

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10 pages, 1349 KiB

Open AccessArticle

Pestalotiones A–D: Four New Secondary Metabolites from the Plant Endophytic Fungus Pestalotiopsis Theae

by Longfang Guo, Jie Lin, Shubin Niu, Shuchun Liu and Ling Liu

Molecules 2020, 25(3), 470; https://doi.org/10.3390/molecules25030470 - 22 Jan 2020

Cited by 17 | Viewed by 3562

Abstract

Two new xanthone derivatives, pestalotiones A (1) and B (2), one new diphenyl ketone riboside, pestalotione C (7), and one new diphenyl ether, pestalotione D (8), along with five known compounds isosulochrin dehydrate (3 [...] Read more.

Two new xanthone derivatives, pestalotiones A (1) and B (2), one new diphenyl ketone riboside, pestalotione C (7), and one new diphenyl ether, pestalotione D (8), along with five known compounds isosulochrin dehydrate (3), 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), isosulochrin (5), chloroisosulochrin (6), and pestalotether D (9), were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). The structures of the new compounds were unambiguously deduced by HRESIMS and 1D/2D-NMR spectroscopic data. Compound 6 showed modest cytotoxicity against the HeLa cell line with an IC₅₀ value of 35.2 μM. Compound 9 also showed cytotoxic to the HeLa and MCF-7 cell lines, with IC₅₀ values of 60.8 and 22.6 μM, respectively. Additionally, compounds 1 and 2 exhibited antioxidant activity in scavenging DPPH radical with IC₅₀ values of 54.2 and 59.2 μg/mL, respectively. Full article

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17 pages, 2748 KiB

Open AccessArticle

Effects of Orange Extracts on Longevity, Healthspan, and Stress Resistance in Caenorhabditis elegans

by Jing Wang, Na Deng, Hong Wang, Tong Li, Ling Chen, Bisheng Zheng and Rui Hai Liu

Molecules 2020, 25(2), 351; https://doi.org/10.3390/molecules25020351 - 15 Jan 2020

Cited by 60 | Viewed by 6598

Abstract

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on [...] Read more.

Orange, with various bioactive phytochemicals, exerts various beneficial health effects, including anti-cancer, antioxidant, and anti-inflammatory properties. However, its anti-aging effects remain unclear. In this study, the Caenorhabditis elegans (C. elegans) model was used to evaluate the effects of orange extracts on lifespan and stress resistance. The results indicated that orange extracts dose-dependently increased the mean lifespan of C. elegans by 10.5%, 18.0%, and 26.2% at the concentrations of 100, 200, and 400 mg/mL, respectively. Meanwhile, orange extracts promoted the healthspan by improving motility, and decreasing the accumulation of age pigment and intracellular reactive oxygen species (ROS) levels without damaging fertility. The survival rates of orange extract-fed worms were obviously higher than those of untreated worms against thermal and ultraviolet-B (UV-B) stress. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly enhanced while malondialdehyde (MDA) contents were diminished. Further investigation revealed that worms supplemented with orange extracts resulted in upregulated levels of genes, including daf-16, sod-3, gst-4, sek-1, and skn-1, and the downregulation of age-1 expression. These findings revealed that orange extracts have potential anti-aging effects through extending the lifespan, enhancing stress resistance, and promoting the healthspan. Full article

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2019

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8 pages, 1536 KiB

Open AccessCommunication

An Autophagy Inducing Triterpene Saponin Derived from Aster koraiensis

by Jaeyoung Kwon, Keebeom Ko, Lijun Zhang, Dong Zhao, Hyun Ok Yang and Hak Cheol Kwon

Molecules 2019, 24(24), 4489; https://doi.org/10.3390/molecules24244489 - 7 Dec 2019

Cited by 11 | Viewed by 3571

Abstract

Autophagy is an important self-degradative mechanism that plays a key role in treating neurodegeneration diseases. This research aimed at discovering bioactive compounds from Aster koraiensis. A new triterpene saponin, astersaponin I (1), was isolated from the EtOH extract of A. [...] Read more.

Autophagy is an important self-degradative mechanism that plays a key role in treating neurodegeneration diseases. This research aimed at discovering bioactive compounds from Aster koraiensis. A new triterpene saponin, astersaponin I (1), was isolated from the EtOH extract of A. koraiensis. The structure of 1 was characterized by spectroscopic methods, ECD calculation, and acid hydrolysis. The biochemical analysis showed that compound 1 significantly increased the expression of microtubule-associated protein 1A/1B light chain 3B (LC3-II) expression in SH-SY5Y cells, which indicates the induction of autophagy. Thus, further study may be needed to clarify whether compound 1 exerts beneficial effects on neurodegeneration diseases like Parkinson’s disease through autophagy induction. Full article

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15 pages, 1257 KiB

Open AccessReview

The Genus Nerine Herb. (Amaryllidaceae): Ethnobotany, Phytochemistry, and Biological Activity

by Lucie Cahlíková, Nina Vaněčková, Marcela Šafratová, Kateřina Breiterová, Gerald Blunden, Daniela Hulcová and Lubomír Opletal

Molecules 2019, 24(23), 4238; https://doi.org/10.3390/molecules24234238 - 21 Nov 2019

Cited by 20 | Viewed by 4827

Abstract

Nerine Herbert, family Amaryllidaceae, is a genus of about 30 species that are native to South Africa, Botswana, Lesotho, Namibia, and Swatini (formerly known as Swaziland). Species of Nerine are autumn-flowering, perennial, bulbous plants, which inhabit areas with summer rainfall and cool, dry [...] Read more.

Nerine Herbert, family Amaryllidaceae, is a genus of about 30 species that are native to South Africa, Botswana, Lesotho, Namibia, and Swatini (formerly known as Swaziland). Species of Nerine are autumn-flowering, perennial, bulbous plants, which inhabit areas with summer rainfall and cool, dry winters. Most Nerine species have been cultivated for their elegant flowers, presenting a source of innumerable horticultural hybrids. For many years, species of Nerine have been subjected to extensive phytochemical and pharmacological investigations, which resulted in either the isolation or identification of more than fifty Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Nerine. Full article

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18 pages, 1362 KiB

Open AccessReview

Mushrooms of the Genus Ganoderma Used to Treat Diabetes and Insulin Resistance

by Katarzyna Wińska, Wanda Mączka, Klaudia Gabryelska and Małgorzata Grabarczyk

Molecules 2019, 24(22), 4075; https://doi.org/10.3390/molecules24224075 - 11 Nov 2019

Cited by 59 | Viewed by 7514

Abstract

Pharmacotherapy using natural substances can be currently regarded as a very promising future alternative to conventional therapy of diabetes mellitus, especially in the case of chronic disease when the body is no longer able to produce adequate insulin or when it cannot use [...] Read more.

Pharmacotherapy using natural substances can be currently regarded as a very promising future alternative to conventional therapy of diabetes mellitus, especially in the case of chronic disease when the body is no longer able to produce adequate insulin or when it cannot use the produced insulin effectively. This minireview summarizes the perspectives, recent advances, and major challenges of medicinal mushrooms from Ganoderma genus with reference to their antidiabetic activity. The most active ingredients of those mushrooms are polysaccharides and triterpenoids. We hope this review can offer some theoretical basis and inspiration for the mechanism study of the bioactivity of those compounds. Full article

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12 pages, 3006 KiB

Open AccessArticle

Investigation on the Antifungal Ingredients of Saccharothrix Yanglingensis Hhs.015, an Antagonistic Endophytic Actinomycete Isolated from Cucumber Plant

by Hua Wang, Runze Tian, Qizhen Tian, Xia Yan, Lili Huang and Zhiqin Ji

Molecules 2019, 24(20), 3686; https://doi.org/10.3390/molecules24203686 - 13 Oct 2019

Cited by 11 | Viewed by 3459

Abstract

Apple tree canker infected by Valsa mali var. mali is a serious and widely distributed disease in China. Saccharothrix yanglingensis Hhs.015 is an endophytic actinomycete isolated from cucumber roots, and it has been proven that this strain is a promising biocontrol agent on [...] Read more.

Apple tree canker infected by Valsa mali var. mali is a serious and widely distributed disease in China. Saccharothrix yanglingensis Hhs.015 is an endophytic actinomycete isolated from cucumber roots, and it has been proven that this strain is a promising biocontrol agent on apple tree canker in previous studies. The aim of this study was to elucidate the active ingredients in its metabolites. Two pentaene macrolides, WH01 and WH02, were isolated from strain Hhs.015, and their structures were elucidated based on the extensive spectroscopic analysis. WH01 and WH02 were identified as fungichromin and 1′-deoxyfungichromin, among which WH02 is a novel compound. These two compounds showed strong in vitro and in vivo antifungal activity against V. mali. By comparison of the structures of hyphae cells treated by pure compound and fermentation broth, it has been proven that pentaene macrolides are the main active ingredients in the metabolites of strain Hhs.015. This is the first report on the antifungal activity of fungichromin and its analogs on V. mali, and the 28-member pentaene macrolides were also firstly isolated from the genus of Saccharothrix. Full article

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20 pages, 6708 KiB

Open AccessArticle

Characterization, Antioxidant, Anti-Aging and Organ Protective Effects of Sulfated Polysaccharides from Flammulina velutipes

by Fangfang Yuan, Zheng Gao, Wenbo Liu, Huaping Li, Yiwen Zhang, Yanbo Feng, Xinling Song, Wenshuai Wang, Jianjun Zhang, Chunyan Huang and Le Jia

Molecules 2019, 24(19), 3517; https://doi.org/10.3390/molecules24193517 - 28 Sep 2019

Cited by 56 | Viewed by 4936

Abstract

As an irreversible and complex degenerative physiological process, the treatment for aging seems strategically necessary, and polysaccharides play important roles against aging owing to their abundant bioactivities. In this paper, the antioxidant and anti-aging activities of Flammulina velutipes polysaccharides (FPS) and its sulfated [...] Read more.

As an irreversible and complex degenerative physiological process, the treatment for aging seems strategically necessary, and polysaccharides play important roles against aging owing to their abundant bioactivities. In this paper, the antioxidant and anti-aging activities of Flammulina velutipes polysaccharides (FPS) and its sulfated FPS (SFPS) on d-galactose-induced aging mice were investigated. The in vitro antioxidant activities demonstrated that SFPS had strong reducing power and superior scavenging effects on 2, 2-diphenylpicrylhydrazyl (DPPH), hydroxyl radicals and the chelating activities of Fe²⁺. The in vivo animal experiments manifested that the SFPS showed superior antioxidant and protective abilities against the d-galactose-induced aging by increasing the antioxidant enzyme activities, decreasing lipid peroxidation, improving the inflammatory response and ameliorating the anile condition of mice. Furthermore, the structural analysis of SFPS was investigated through FT-IR, NMR, and HPLC analysis, and the results indicated that SFPS was a homogeneous heteropolysaccharide with a weight-average molecular weight of 2.81 × 10³ Da. Furthermore, SFPS has also changed in characteristic functional groups and monosaccharide composition compared to FPS. These results suggested that sulfated modification could enhance the anti-oxidation, anti-aging and protective activities of F. velutipes polysaccharides, which may provide references for the development of functional foods and natural medicines. Full article

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11 pages, 642 KiB

Open AccessArticle

Accramycin A, A New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

by Fleurdeliz Maglangit, Qing Fang, Valentin Leman, Sylvia Soldatou, Rainer Ebel, Kwaku Kyeremeh and Hai Deng

Molecules 2019, 24(18), 3384; https://doi.org/10.3390/molecules24183384 - 17 Sep 2019

Cited by 32 | Viewed by 5706

Abstract

Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain [...] Read more.

Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed. Full article

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12 pages, 4395 KiB

Open AccessArticle

Antioxidant Effect of Extracts from Native Chilean Plants on the Lipoperoxidation and Protein Oxidation of Bovine Muscle

by Raquel Bridi, Ady Giordano, Maria Fernanda Peñailillo and Gloria Montenegro

Molecules 2019, 24(18), 3264; https://doi.org/10.3390/molecules24183264 - 7 Sep 2019

Cited by 14 | Viewed by 3865

Abstract

The present study investigated the antioxidant potential and the ability to inhibit lipid and protein oxidation in bovine meat of four native Chilean species: canelo (Drimys winteri), nalca (Gunnera tinctoria), tiaca (Caldcluvia paniculata), and ulmo (Eucryphia [...] Read more.

The present study investigated the antioxidant potential and the ability to inhibit lipid and protein oxidation in bovine meat of four native Chilean species: canelo (Drimys winteri), nalca (Gunnera tinctoria), tiaca (Caldcluvia paniculata), and ulmo (Eucryphia cordifolia). Phenolic acids (gallic, chlorogenic, caffeic, and coumaric) and flavonoids (catechin, epicatechin, and rutin) were identified and quantified by HPLC-MS/MS. Drimys winteri extract exhibited the highest antioxidant capacity evaluated by oxygen radical absorption capacity-red pyrogallol method (ORAC-PGR) and ferric ion reducing antioxidant power (FRAP) assays. All extracts decreased lipid oxidation induced by 2,2’-azo-bis(2-amidinopropane) dihydrochloride (AAPH) derived peroxyl radicals by anywhere between 30% and 50% the. In addition, canelo and nalca extracts decreased spontaneous oxidation by around 57% and 37% in relation to the control group, being even more efficient than butylated hydroxyanisole (BHT) a synthetic antioxidant. Protein oxidation in the myofibrillar proteins was evaluated by the formation of protein carbonyls and loss of protein thiols. The canelo, ulmo, and nalca extracts decreased the formation of carbonyls by around 30%. Plant extracts and BHT did not show an antioxidant effect on protein thiol loss. However, tiaca and ulmo extracts exerted a pro-oxidant effect, favoring the oxidation of sulfhydryl groups. The oxidizing system induced structural changes in myofibrillar protein (SDS−PAGE). A protective effect on protein structure from the canelo extract can be observed during the incubation when compared to samples incubated with AAPH. Full article

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9 pages, 672 KiB

Open AccessCommunication

New Sesquiterpenoids from the Fermented Broth of Termitomyces albuminosus and Their Anti-Acetylcholinesterase Activity

by Wei Li, Qian Liu, Shimian Cheng, Shanren Li and Yongbiao Zheng

Molecules 2019, 24(16), 2980; https://doi.org/10.3390/molecules24162980 - 16 Aug 2019

Cited by 14 | Viewed by 3334

Abstract

Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids—teucdiol C (1), D (2), E (3 [...] Read more.

Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids—teucdiol C (1), D (2), E (3), and F (4), together with two known sesquiterpenoids teucdiol B (5) and epi-guaidiol A (6)—were obtained from its fermented broth of T. albuminosus. Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction. Epi-guaidiol A showed obvious anti-acetylcholinesterase activity in a dose-dependent manner. The experimental results displayed that T. albuminosus possess the pharmaceutical potential for Alzheimer’s disease, and it was an effective way to dig new pharmaceutical agent of T. albuminosus with the microbial fermentation technique. Full article

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16 pages, 1973 KiB

Open AccessArticle

Differences in the Moisture Capacity and Thermal Stability of Tremella fuciformis Polysaccharides Obtained by Various Drying Processes

by Chun-Ping Lin and Shu-Yao Tsai

Molecules 2019, 24(15), 2856; https://doi.org/10.3390/molecules24152856 - 6 Aug 2019

Cited by 32 | Viewed by 5776

Abstract

We compared the proportions and differences in the polysaccharides of Tremella fuciformis (Berkeley) after drying them by various processes, such as 18 °C cold air, 50 °C hot air, and freeze-drying. We also focused on the moisture capacity kinetic parameters of Tremella fuciformis [...] Read more.

We compared the proportions and differences in the polysaccharides of Tremella fuciformis (Berkeley) after drying them by various processes, such as 18 °C cold air, 50 °C hot air, and freeze-drying. We also focused on the moisture capacity kinetic parameters of Tremella fuciformis polysaccharides using various thermal analyses, including differential scanning calorimetry and thermogravimetric techniques. Erofeev’s kinetic and proto-kinetic equations, utilized for kinetic model simulation, can predict the moisture capacity due to the thermal effect. Among the various drying processes, cold air-drying had the highest molecular weight of 2.41 × 10⁷ Da and a moisture content of 13.05% for Tremella fuciformis polysaccharides. Overall, the freeze-dried products had the best thermal decomposition properties under the conditions of a closed system, with an air or nitrogen atmosphere, and had an excellent moisture capacity of around 35 kJ/kg under a closed system for all samples. Full article

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10 pages, 829 KiB

Open AccessArticle

Phytotoxic Activity and Structure–Activity Relationships of Radicinin Derivatives against the Invasive Weed Buffelgrass (Cenchrus ciliaris)

by Marco Masi, Fabrizio Freda, Suzette Clement, Alessio Cimmino, Massimo Cristofaro, Susan Meyer and Antonio Evidente

Molecules 2019, 24(15), 2793; https://doi.org/10.3390/molecules24152793 - 31 Jul 2019

Cited by 13 | Viewed by 3322

Abstract

Radicinin (1), is a fungal dihydropyranopyran-4,5-dione isolated together with some analogues, namely 3-epi-radicinin, radicinol, 3-epi-radicinol, and cochliotoxin (2–5), from the culture filtrates of the fungus Cochliobolus australiensis, a foliar pathogen of buffelgrass [...] Read more.

Radicinin (1), is a fungal dihydropyranopyran-4,5-dione isolated together with some analogues, namely 3-epi-radicinin, radicinol, 3-epi-radicinol, and cochliotoxin (2–5), from the culture filtrates of the fungus Cochliobolus australiensis, a foliar pathogen of buffelgrass (Cenchrus ciliaris), an invasive weed in North America. Among the different metabolites 1 showed target-specific activity against the host plant and no toxicity on zebrafish embryos, promoting its potential use to develop a natural bioherbicide formulation to manage buffelgrass. These data and the peculiar structural feature of 1 suggested to carry out a structure-activity relationship study, preparing some key hemisynthetic derivatives and to test their phytotoxicity. In particular, p-bromobenzoyl, 5-azidopentanoyl, stearoyl, mesyl and acetyl esters of radicinin were semisynthesized as well as the monoacetyl ester of 3-epi-radicinin, the diacetyl esters of radicinol and its 3 epimer, and two hexa-hydro derivatives of radicinin. The spectroscopic characterization and the activity by leaf puncture bioassay against buffelgrass of all the derivatives is reported. Most of the compounds showed phytotoxicity but none of them had comparable or higher activity than radicinin. Thus, the presence of an α,β unsaturated carbonyl group at C-4, as well as, the presence of a free secondary hydroxyl group at C-3 and the stereochemistry of the same carbon proved to be the essential feature for activity. Full article

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20 pages, 4095 KiB

Open AccessArticle

The Antioxidant and Anti-Aging Effects of Acetylated Mycelia Polysaccharides from Pleurotus djamor

by Huaping Li, Huajie Zhao, Zheng Gao, Xinling Song, Wenshuai Wang, Fangfang Yuan, Yanbo Feng, Yiwen Zhang, Jianjun Zhang, Shuliang Zhang and Le Jia

Molecules 2019, 24(15), 2698; https://doi.org/10.3390/molecules24152698 - 24 Jul 2019

Cited by 29 | Viewed by 5053

Abstract

The present work mainly describes the preparation of acetylated mycelia polysaccharides (AMPS) from Pleurotus djamor and investigates the antioxidant and anti-aging effects in d-galactose-induced aging mice. The optimized procedure indicates the acetyl substitution degree of AMPS is 0.54 ± 0.04 under the [...] Read more.

The present work mainly describes the preparation of acetylated mycelia polysaccharides (AMPS) from Pleurotus djamor and investigates the antioxidant and anti-aging effects in d-galactose-induced aging mice. The optimized procedure indicates the acetyl substitution degree of AMPS is 0.54 ± 0.04 under the conditions of a reaction time of 56 h, a reaction temperature of 37 °C, and 4 mL of added acetic anhydride. The in vitro analysis and in vivo animal experiments indicate that the AMPS could alleviate the aging properties by scavenging the radicals, elevating the enzyme activities, and reducing the lipid contents. As for serum levels, the AMPS can improve the serum biochemical indices and enhance immunological activity. The histopathological observations indicate that the injuries to the liver, kidney, and brain can be remitted by AMPS intervention. The characterization showed that AMPS was one kind of β-pyranose with the weight-average molecular weights of 3.61 × 10⁵ Da and the major monosaccharides of mannose and glucose. The results suggest that AMPS can be used as a dietary supplement and functional food for the prevention of aging and age-related diseases. Full article

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21 pages, 9020 KiB

Open AccessArticle

The Antiglycoxidative Ability of Selected Phenolic Compounds—An In Vitro Study

by Agnieszka Piwowar, Anna Rorbach-Dolata and Izabela Fecka

Molecules 2019, 24(15), 2689; https://doi.org/10.3390/molecules24152689 - 24 Jul 2019

Cited by 27 | Viewed by 3318

Abstract

Hyperglycemia and oxidative stress may be observed in different diseases as important factors connected with their development. They often occur simultaneously and are considered together as one process: Glycoxidation. This can influence the function or structure of many macromolecules, for example albumin, by [...] Read more.

Hyperglycemia and oxidative stress may be observed in different diseases as important factors connected with their development. They often occur simultaneously and are considered together as one process: Glycoxidation. This can influence the function or structure of many macromolecules, for example albumin, by changing their physiological properties. This disturbs the homeostasis of the organism, so the search for natural compounds able to inhibit the glycoxidation process is a current and important issue. The aim of this study was the examination of the antiglycoxidative capacity of 16 selected phenolic compounds, belonging to three phenolic groups, as potential therapeutic agents. Their antiglycoxidative ability, in two concentrations (2 and 20 µM), were examined by in vitro study. The inhibition of the formation of both glycoxidative products (advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)) were assayed. Stronger antiglycoxidative action toward the formation of both AOPPs and AGEs was observed for homoprotocatechuic and ferulic acids in lower concentrations, as well as catechin, quercetin, and 8-O-methylurolithin A in higher concentrations. Homoprotocatechuic acid demonstrated the highest antiglycoxidative capacity in both examined concentrations and amongst all of them. A strong, significant correlation between the percentage of AOPPs and AGEs inhibition by compounds from all phenolic groups, in both examined concentrations, was observed. The obtained results give an insight into the antiglycoxidative potential of phenolic compounds and indicate homoprotocatechuic acid to be the most promising antiglycoxidative agent, but further biological and pharmacological studies are needed. Full article

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15 pages, 463 KiB

Open AccessArticle

Solidago graminifolia L. Salisb. (Asteraceae) as a Valuable Source of Bioactive Polyphenols: HPLC Profile, In Vitro Antioxidant and Antimicrobial Potential

by Anca Toiu, Laurian Vlase, Dan Cristian Vodnar, Ana-Maria Gheldiu and Ilioara Oniga

Molecules 2019, 24(14), 2666; https://doi.org/10.3390/molecules24142666 - 23 Jul 2019

Cited by 39 | Viewed by 4863

Abstract

Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of [...] Read more.

Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities. Full article

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9 pages, 972 KiB

Open AccessArticle

Inhibitory Activity of Plant Essential Oils against E. coli 1-Deoxy-d-xylulose-5-phosphate reductoisomerase

by Ge Yan, Bo-Rong Zhu, Fang-Lin Tian, Xian Hui, Heng Li, Yi-Ming Li and Wen-Yun Gao

Molecules 2019, 24(14), 2518; https://doi.org/10.3390/molecules24142518 - 10 Jul 2019

Cited by 7 | Viewed by 3231

Abstract

The rate-limiting enzyme of the 2-methyl-d-erythritol-4-phosphate (MEP) terpenoid biosynthetic pathway, 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), provides the perfect target for screening new antibacterial substances. In this study, we tested the DXR inhibitory effect of 35 plant essential oils (EOs), which have [...] Read more.

The rate-limiting enzyme of the 2-methyl-d-erythritol-4-phosphate (MEP) terpenoid biosynthetic pathway, 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), provides the perfect target for screening new antibacterial substances. In this study, we tested the DXR inhibitory effect of 35 plant essential oils (EOs), which have long been recognized for their antimicrobial properties. The results show that the EOs of Zanbthoxylum bungeanum (ZB), Schizonepetae tenuifoliae (ST), Thymus quinquecostatus (TQ), Origanum vulgare (OV), and Eugenia caryophyllata (EC) displayed weak to medium inhibitory activity against DXR, with IC₅₀ values of 78 μg/mL, 65 μg/mL, 59 μg/mL, 48 μg/mL, and 37 μg/mL, respectively. GC-MS analyses of the above oils and further DXR inhibitory activity tests of their major components revealed that eugenol (EC) and carvacrol (TQ and OV) possess medium inhibition against the protein (68.3% and 55.6%, respectively, at a concentration of 20 μg/mL), whereas thymol (ST, TQ, and OV), carveol (ZB), and linalool (ZB, ST, and OV) only exhibited weak inhibition against DXR, at 20 μg/mL (23%−26%). The results add more details to the antimicrobial mechanisms of plant EOs, which could be very helpful in the direction of the reasonable use of EOs in the food industry and in the control of phytopathogenic microbials. Full article

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11 pages, 268 KiB

Open AccessFeature PaperArticle

A Comparative Study of Black and White Allium sativum L.: Nutritional Composition and Bioactive Properties

by Joana Botas, Ângela Fernandes, Lillian Barros, Maria José Alves, Ana Maria Carvalho and Isabel C.F.R. Ferreira

Molecules 2019, 24(11), 2194; https://doi.org/10.3390/molecules24112194 - 11 Jun 2019

Cited by 35 | Viewed by 5415

Abstract

Garlic (Allium sativum L.) has been used worldwide not only for its being a subject of dietary interest, but also for medicinal purposes, in prophylaxis, and for the treatment of diverse pathologies. New processing techniques have been developed and placed on the [...] Read more.

Garlic (Allium sativum L.) has been used worldwide not only for its being a subject of dietary interest, but also for medicinal purposes, in prophylaxis, and for the treatment of diverse pathologies. New processing techniques have been developed and placed on the market in recent years to improve the organoleptic and nutritional value of food products. The present work aimed to study bulbils (cloves) of white (commercial and traditionally cultivated samples with different proveniences) and black (processed samples) garlic. All samples were compared with regard to their nutritional composition as well as their antioxidant and antimicrobial activities. Black garlic had the lowest moisture content but the highest total amount of sugars and energetic value. Black garlic also presented the highest antioxidant and antimicrobial (especially against methicillin-resistant Staphylococcus aureus) activities. Thus, black garlic, obtained by processing techniques, can be considered a promising product with high value that will be able to be exploited by the functional food/nutraceutical industry. Full article

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11 pages, 239 KiB

Open AccessArticle

In Vitro Human Metabolism and Inhibition Potency of Verbascoside for CYP Enzymes

by Anna-Mari Reid, Risto Juvonen, Pasi Huuskonen, Marko Lehtonen, Markku Pasanen and Namrita Lall

Molecules 2019, 24(11), 2191; https://doi.org/10.3390/molecules24112191 - 11 Jun 2019

Cited by 12 | Viewed by 3564

Abstract

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism [...] Read more.

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism in human hepatic microsomes and cytosol incubations as well as the presence and quantity of verbascoside within Lippia scaberrima. Additionally, studied are the inhibitory properties on human hepatic CYP enzymes together with antioxidant and cytotoxic properties. The results yielded no metabolites in the hydrolysis or cytochrome P450 (CYP) oxidation incubations. However, five different methylated conjugates of verbascoside could be found in S-adenosylmethionine incubation, three different sulphate conjugates with 3′-phosphoadenosine 5′-phosphosulfate (PAPS) incubation with human liver samples, and very low levels of glucuronide metabolites after incubation with recombinant human uridine 5’-diphospho-glucuronosyltransferase (UGT) 1A7, UGT1A8, and UGT1A10. Additionally, verbascoside showed weak inhibitory potency against CYP1A2 and CYP1B1 with IC₅₀ values of 83 µM and 86 µM, respectively. Potent antioxidant and low cytotoxic potential were observed. Based on these data, verbascoside does not possess any clinically relevant CYP-mediated interaction potential, but it has effective biological activity. Therefore, verbascoside could be considered as a lead compound for further drug development and as an adjuvant during tuberculosis treatment. Full article

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11 pages, 780 KiB

Open AccessCommunication

Anti-Inflammatory Compounds from Atractylodes macrocephala

by Dawoon Jeong, Guang-zhi Dong, Hwa Jin Lee and Jae-Ha Ryu

Molecules 2019, 24(10), 1859; https://doi.org/10.3390/molecules24101859 - 14 May 2019

Cited by 27 | Viewed by 4374

Abstract

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1 [...] Read more.

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases. Full article

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14 pages, 1965 KiB

Open AccessReview

A Review on Daphnane-Type Diterpenoids and Their Bioactive Studies

by Yue-Xian Jin, Lei-Ling Shi, Da-Peng Zhang, Hong-Yan Wei, Yuan Si, Guo-Xu Ma and Jing Zhang

Molecules 2019, 24(9), 1842; https://doi.org/10.3390/molecules24091842 - 13 May 2019

Cited by 38 | Viewed by 6130

Abstract

Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat [...] Read more.

Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019. Full article

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12 pages, 466 KiB

Open AccessFeature PaperArticle

Phenolic Profile and Bioactive Properties of Carissa macrocarpa (Eckl.) A.DC.: An In Vitro Comparative Study between Leaves, Stems, and Flowers

by Fedia Souilem, Maria Inês Dias, Lillian Barros, Ricardo C. Calhelha, Maria José Alves, Fethia Harzallah-Skhiri and Isabel C.F.R. Ferreira

Molecules 2019, 24(9), 1696; https://doi.org/10.3390/molecules24091696 - 30 Apr 2019

Cited by 25 | Viewed by 4075

Abstract

The present work aimed to characterize leaves, stems, and flowers of Carissa macrocarpa (Eckl.) A.DC., by performing an analysis of the phenolic compounds by HPLC-DAD/ESI-MS, correlating them with bioactive properties, such as antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities. Thirty polyphenols were identified in [...] Read more.

The present work aimed to characterize leaves, stems, and flowers of Carissa macrocarpa (Eckl.) A.DC., by performing an analysis of the phenolic compounds by HPLC-DAD/ESI-MS, correlating them with bioactive properties, such as antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities. Thirty polyphenols were identified in the hydroethanolic extract, including phenolic acids, flavan-3-ols, and flavonol glycosides derivatives (which presented the highest number of identified compounds). However, flavan-3-ols showed the highest concentration in stems (mainly owing to the presence of dimers, trimmers, and tetramers of type B (epi)catechin). Leaves were distinguished by their high antioxidant and anti-inflammatory activities, as well as their bactericidal effect against E. coli, while stems presented a higher cytotoxic activity and bactericidal effect against Gram-positive bacteria. Moreover, a high correlation between the studied bioactivities and the presence of phenolic compounds was also verified. The obtained results bring added value to the studied plant species. Full article

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13 pages, 3903 KiB

Open AccessArticle

Anticancer Effects of Five Biflavonoids from Ginkgo Biloba L. Male Flowers In Vitro

by Min Li, Bin Li, Zi-Ming Xia, Ying Tian, Dan Zhang, Wen-Jing Rui, Jun-Xing Dong and Feng-Jun Xiao

Molecules 2019, 24(8), 1496; https://doi.org/10.3390/molecules24081496 - 16 Apr 2019

Cited by 69 | Viewed by 5700

Abstract

Ginkgo biloba L., an ancient dioecious gymnosperm, is now cultivated worldwide for landscaping and medical purposes. A novel biflavonoid—amentoflavone 7′′-O-β-d-glucopyranoside (1)—and four known biflavonoids were isolated and identified from the male flowers of Ginkgo. The anti-proliferative [...] Read more.

Ginkgo biloba L., an ancient dioecious gymnosperm, is now cultivated worldwide for landscaping and medical purposes. A novel biflavonoid—amentoflavone 7′′-O-β-d-glucopyranoside (1)—and four known biflavonoids were isolated and identified from the male flowers of Ginkgo. The anti-proliferative activities of five biflavonoids were evaluated on different cancer lines. Bilobetin (3) and isoginkgetin (4) exhibited better anti-proliferative activities on different cancer lines. Their effects were found to be cell-specific and in a dose and time dependent manner for the most sensitive HeLa cells. The significant morphological changes validated their anticancer effects in a dose-dependent manner. They were capable of arresting the G2/M phase of the cell cycle, inducing the apoptosis of HeLa cells dose-dependently and activating the proapoptotic protein Bax and the executor caspase-3. Bilobetin (3) could also inhibit the antiapoptotic protein Bcl-2. These might be the mechanism underlying their anti-proliferation. In short, bilobetin (3) and isoginkgetin (4) might be the early lead compounds for new anticancer agents. Full article

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8 pages, 708 KiB

Open AccessArticle

Discovery of Nosiheptide, Griseoviridin, and Etamycin as Potent Anti-Mycobacterial Agents against Mycobacterium avium Complex

by Kanji Hosoda, Nobuhiro Koyama, Akihiko Kanamoto and Hiroshi Tomoda

Molecules 2019, 24(8), 1495; https://doi.org/10.3390/molecules24081495 - 16 Apr 2019

Cited by 17 | Viewed by 4352

Abstract

Mycobacterium avium complex (MAC) is a serious disease mainly caused by M. avium and M. intracellulare. Although the incidence of MAC infection is increasing worldwide, only a few agents are clinically used, and their therapeutic effects are limited. Therefore, new anti-MAC agents are [...] Read more.

Mycobacterium avium complex (MAC) is a serious disease mainly caused by M. avium and M. intracellulare. Although the incidence of MAC infection is increasing worldwide, only a few agents are clinically used, and their therapeutic effects are limited. Therefore, new anti-MAC agents are needed. Approximately 6600 microbial samples were screened for new anti-mycobacterial agents that inhibit the growth of both M. avium and M. intracellulare, and two culture broths derived from marine actinomycete strains OPMA1245 and OPMA1730 had strong activity. Nosiheptide (1) was isolated from the culture broth of OPMA1245, and griseoviridin (2) and etamycin (viridogrisein) (3) were isolated from the culture broth of OPMA1730. They had potent anti-mycobacterial activity against M. avium and M. intracellulare with minimum inhibitory concentrations (MICs) between 0.024 and 1.56 μg/mL. In addition, a combination of 2 and 3 markedly enhanced the anti-mycobacterial activity against both M. avium and M. intracellulare. Furthermore, a combination 2 and 3 had a therapeutic effect comparable to that of ethambutol in a silkworm infection assay with M. smegmatis. Full article

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9 pages, 780 KiB

Open AccessCommunication

A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study

by Xiaoyong Zheng, Feng Feng, Xiunan Jiang, Jieying Qiu, Xiaojun Cai and Zheng Xiang

Molecules 2019, 24(7), 1403; https://doi.org/10.3390/molecules24071403 - 10 Apr 2019

Cited by 5 | Viewed by 3077

Abstract

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer’s agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry [...] Read more.

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer’s agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL (R² = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2–86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D. Full article

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20 pages, 3873 KiB

Open AccessReview

Alcyonium Octocorals: Potential Source of Diverse Bioactive Terpenoids

by Ahmed Abdel-Lateff, Walied Mohamed Alarif, Najla Ali Alburae and Mardi Mohamed Algandaby

Molecules 2019, 24(7), 1370; https://doi.org/10.3390/molecules24071370 - 8 Apr 2019

Cited by 18 | Viewed by 4302

Abstract

Alcyonium corals are benthic animals, which live in different climatic areas, including temperate, Antarctic and sub-Antarctic waters. They were found to produce different chemical substances with molecular diversity and unique architectures. These metabolites embrace several terpenoidal classes with different functionalities. This wide array [...] Read more.

Alcyonium corals are benthic animals, which live in different climatic areas, including temperate, Antarctic and sub-Antarctic waters. They were found to produce different chemical substances with molecular diversity and unique architectures. These metabolites embrace several terpenoidal classes with different functionalities. This wide array of structures supports the productivity of genus Alcyonium. Yet, majority of the reported compounds are still biologically unscreened and require substantial efforts to explore their importance. This review is an entryway to push forward the bio-investigation of this genus. It covers the era from the beginning of reporting metabolites from Alcyonium up to March 2019. Ninety-two metabolites are presented; forty-two sesquiterpenes, twenty-five diterpenes and twenty-five steroids have been reported from sixteen species. Full article

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9 pages, 571 KiB

Open AccessArticle

The Impact of Processing Parameters on the Content of Phenolic Compounds in New Gluten-Free Precooked Buckwheat Pasta

by Anna Oniszczuk, Kamila Kasprzak, Agnieszka Wójtowicz, Tomasz Oniszczuk and Marta Olech

Molecules 2019, 24(7), 1262; https://doi.org/10.3390/molecules24071262 - 1 Apr 2019

Cited by 12 | Viewed by 3477

Abstract

Buckwheat is a generous source of phenolic compounds, vitamins and essential amino acids. This paper discusses the procedure of obtaining innovative gluten-free, precooked pastas from roasted buckwheat grains flour, a fertile source of natural antioxidants, among them, phenolic acids. The authors also determined [...] Read more.

Buckwheat is a generous source of phenolic compounds, vitamins and essential amino acids. This paper discusses the procedure of obtaining innovative gluten-free, precooked pastas from roasted buckwheat grains flour, a fertile source of natural antioxidants, among them, phenolic acids. The authors also determined the effect of the extruder screw speed and the level of moisture content in the raw material on the quantity of free phenolic acids. The qualitative and quantitative analysis of phenolic acids in pasta was carried out using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The chromatographic method was validated. For extracts with the highest total content of free phenolic acids and unprocessed flour from roasted buckwheat grain, the TLC-DPPH test was also performed to determine the antioxidant properties of the tested pasta. The level of moisture in the raw material had an impact on the content of phenolic acids. All pastas made from buckwheat flour moistened up to 32% exhibited a higher total content of free phenolic acids than other mixes moistened to 30 and 34% of water. Full article

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13 pages, 2200 KiB

Open AccessArticle

Four Novel Dammarane-Type Triterpenoids from Pearl Knots of Panax ginseng Meyer cv. Silvatica

by Zeng Qi, Zhuo Li, Xuewa Guan, Cuizhu Wang, Fang Wang, Pingya Li and Jinping Liu

Molecules 2019, 24(6), 1159; https://doi.org/10.3390/molecules24061159 - 23 Mar 2019

Cited by 7 | Viewed by 3490

Abstract

Panax ginseng Meyer cv. Silvatica (PGS), which is also known as “Lin-Xia-Shan-Shen” or “Zi-Hai” in China, is grown in forests and mountains by broadcasting the seeds of ginseng and is harvested at the cultivation age of 15–20 years. In this study, four new [...] Read more.

Panax ginseng Meyer cv. Silvatica (PGS), which is also known as “Lin-Xia-Shan-Shen” or “Zi-Hai” in China, is grown in forests and mountains by broadcasting the seeds of ginseng and is harvested at the cultivation age of 15–20 years. In this study, four new dammarane-type triterpenoids, ginsengenin-S1 (1), ginsengenin-S2 (2), ginsenoside-S3 (3), ginsenoside-S4 (4), along with one known compound were isolated from pearl knots of PGS. Ginsengenin-S2 significantly alleviated oxidative damage when A549 cells were exposed to cigarette smoke (CS) extract. In addition, ginsengenin-S2 could inhibit the CS-induced inflammatory reaction in A549 cells. Protective effects of ginsengenin-S2 against CS-mediated oxidative stress and the inflammatory response in A549 cells may involve the Nrf2 and HDAC2 pathways. Full article

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10 pages, 933 KiB

Open AccessFeature PaperArticle

Cytinus hypocistis (L.) L. subsp. macranthus Wettst.: Nutritional Characterization

by Ana Rita Silva, Ângela Fernandes, Pablo A. García, Lillian Barros and Isabel C.F.R. Ferreira

Molecules 2019, 24(6), 1111; https://doi.org/10.3390/molecules24061111 - 20 Mar 2019

Cited by 12 | Viewed by 4233

Abstract

The habit of eating wild plants in Europe is often associated with times of famine; an example of such is the nectar of Cytinus hypocistis (L.) L., a parasitic plant. To the authors’ best knowledge, there are no studies on its nutritional and [...] Read more.

The habit of eating wild plants in Europe is often associated with times of famine; an example of such is the nectar of Cytinus hypocistis (L.) L., a parasitic plant. To the authors’ best knowledge, there are no studies on its nutritional and chemical composition; thus, the whole C. hypocistis (L.) L. subsp. macranthus Wettst. plant (CH) and its nectar (NCH) were nutritionally and chemically characterized. The proximate composition of CH and NCH were very similar in terms of energy, ash, and carbohydrate content. Protein and fat were approximately 2-fold higher in NCH, and crude fiber was 4.6-fold higher in CH compared to NCH. Fructose, glucose, sucrose, and trehalose were the free sugars present in both samples. Oxalic, malic, and citric acids were the identified organic acids in both samples, with citric acid as the most abundant molecule. For both samples, polyunsaturated and saturated fatty acids (PUFA and SFA, respectively) predominate over monounsaturated fatty acids (MUFA) due to the significant contribution of linoleic and palmitic acids, respectively. However, unsaturated fatty acids (UFA) prevail over SFA in CH and NCH. Therefore, CH proved to be an excellent source of nutritional compounds, which supports its use during past periods of scarcity. Full article

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15 pages, 1030 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Phenolic Compounds from Annona muricata By-Products and Pulp

by Gabriela Aguilar-Hernández, María de Lourdes García-Magaña, María de los Ángeles Vivar-Vera, Sonia Guadalupe Sáyago-Ayerdi, Jorge Alberto Sánchez-Burgos, Juliana Morales-Castro, Luis Miguel Anaya-Esparza and Efigenia Montalvo González

Molecules 2019, 24(5), 904; https://doi.org/10.3390/molecules24050904 - 5 Mar 2019

Cited by 50 | Viewed by 5205

Abstract

Ultrasound-assisted extraction (UAE) is widely used; however, the efficiency of extraction depends on the raw materials. Therefore, optimization of UAE must be investigated for each type of plant material. By-products from soursop fruit have not been studied as a source of bioactive compounds. [...] Read more.

Ultrasound-assisted extraction (UAE) is widely used; however, the efficiency of extraction depends on the raw materials. Therefore, optimization of UAE must be investigated for each type of plant material. By-products from soursop fruit have not been studied as a source of bioactive compounds. In this work, the optimization of UAE conditions (extraction time (5, 10, and 15 min), pulse cycle (0.4, 0.7, and 1 s), and sonication amplitude (40%, 70%, and 100%)) for the extraction of phenolic compounds (soluble, hydrolyzable, condensed tannins, and total polyphenols) from soursop by-products (seed, peel, and columella) and pulp was evaluated using response surface methodology. The optimal conditions for UAE to obtain the highest total polyphenol content from by-products and pulp was dependent on the raw material. Peel resulted in the highest content of total polyphenols (187.32 mg/g dry matter [DM]) followed by columella (164.14 mg/g DM), seed (36.15 mg/g DM), and pulp (33.24 mg/g DM). The yield of polyphenolic content from peel and columella obtained with UAE was higher (32–37%) than conventional extraction for 2 h under stirring (14–16%). The contents of gallic acid (0.36–15.86 µg/g DM), coumaric acid (0.07–1.37 µg/g DM), and chlorogenic acid (9.18–32.67 µg/g DM) in the different parts of the fruit were higher in the extracts obtained by UAE compared with a conventional extraction method (0.08–0.61, 0.05–0.08, 3.15–13.08 µg/g DM, respectively), although it was dependent on the raw materials. Soursop by-products can be functionally important if they are used to extract bioactive compounds by UAE; a technology with high potential for commercial extraction on a large scale. Full article

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11 pages, 2416 KiB

Open AccessArticle

Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor

by Chieh-Ju Wu, Mei-Yin Chien, Nan-Hei Lin, Yi-Chiao Lin, Wen-Ying Chen, Chao-Hsiang Chen and Jason T. C. Tzen

Molecules 2019, 24(4), 720; https://doi.org/10.3390/molecules24040720 - 17 Feb 2019

Cited by 20 | Viewed by 7712

Abstract

Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides—echinacoside, tubuloside A, and acteoside—were detected in the water extract of Cistanche tubulosa (Schenk) [...] Read more.

Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides—echinacoside, tubuloside A, and acteoside—were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10⁻⁶ M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg¹, D-Phe⁵, D-Trp^7,9, Leu¹¹]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin. Full article

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24 pages, 989 KiB

Open AccessReview

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

by Asad Ullah, Sidra Munir, Yahia Mabkhot and Syed Lal Badshah

Molecules 2019, 24(4), 678; https://doi.org/10.3390/molecules24040678 - 14 Feb 2019

Cited by 47 | Viewed by 6673

Abstract

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent [...] Read more.

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances. Full article

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8 pages, 728 KiB

Open AccessArticle

Sclerin, a New Cytotoxic Cyclononapeptide from Annona scleroderma

by Francisco Cen-Pacheco, Gerardo Valerio-Alfaro, Dalia Santos-Luna and José Javier Fernández

Molecules 2019, 24(3), 554; https://doi.org/10.3390/molecules24030554 - 3 Feb 2019

Cited by 10 | Viewed by 3872

Abstract

A new cytotoxic cyclononapeptide, sclerin, cyclo(–Dab¹–Ser²–Tyr³–Gly⁴–Thr⁵–Val⁶–Ala⁷– Ile⁸–Pro⁹–) (1), was isolated from the methanol extract of the seeds of Annona scleroderma, together with [...] Read more.

A new cytotoxic cyclononapeptide, sclerin, cyclo(–Dab¹–Ser²–Tyr³–Gly⁴–Thr⁵–Val⁶–Ala⁷– Ile⁸–Pro⁹–) (1), was isolated from the methanol extract of the seeds of Annona scleroderma, together with the known metabolite, cyclosenegalin A, cyclo(–Pro¹–Gly²–Leu³–Ser⁴–Ala⁵–Val⁶–Thr⁷–) (2). The planar structures for the two compounds were established by comprehensive analysis of NMR and ESI-HRMS data, and the absolute stereochemistry was stablished by Marfey’s method. Compound 1 showed moderate cytotoxic activity against the human prostate carcinoma cell line DU-145 at µM concentration. Full article

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8 pages, 1063 KiB

Open AccessCommunication

Discovery of Three New Phytotoxins from the Fungus Aspergillus nidulans by Pathway Inactivation

by Lijuan Liao, Xiaolei Zhang, Yi Lou, Chengzeng Zhou, Qianqian Yuan and Jiangtao Gao

Molecules 2019, 24(3), 515; https://doi.org/10.3390/molecules24030515 - 31 Jan 2019

Cited by 4 | Viewed by 3779

Abstract

Fungi are a source of novel phytotoxic compounds to be explored in the search for effective and environmentally safe herbicides. The genetic inactivation of the biosynthetic pathway of the new phytotoxin cichorine has led to the isolation of three novel phytotoxins from the [...] Read more.

Fungi are a source of novel phytotoxic compounds to be explored in the search for effective and environmentally safe herbicides. The genetic inactivation of the biosynthetic pathway of the new phytotoxin cichorine has led to the isolation of three novel phytotoxins from the fungus Aspergillus nidulans: 8-methoxycichorine (4), 8-epi-methoxycichorine (5), and N-(4’-carboxybutyl) cichorine (6). The structure of the new compounds was clearly determined by a combination of nuclear magnetic resonance (NMR) analysis and high-resolution electrospray ionization (HRESIMS). The phytotoxic bioassay was studied on leaves from Zea mays and Medicago polymorpha L. at the concentration of 5 × 10⁻³ M by using a moist chamber technique. Novel phytotoxins 8-methoxycichorine (4), 8-epi-methoxycichorine (5), and N-(4’-carboxybutyl) cichorine (6) exhibited a better phytotoxic effect than cichorine. Full article

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9 pages, 1226 KiB

Open AccessArticle

Rare Acetogenins with Anti-Inflammatory Effect from the Red Alga Laurencia obtusa

by Walied Mohamed Alarif, Sultan Semran Al-Lihaibi, Nahed Obaid Bawakid, Ahmed Abdel-Lateff and Hamdan Salem Al-malky

Molecules 2019, 24(3), 476; https://doi.org/10.3390/molecules24030476 - 29 Jan 2019

Cited by 4 | Viewed by 3310

Abstract

Three new rare C₁₂ acetogenins (enyne derivatives 1–3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data [...] Read more.

Three new rare C₁₂ acetogenins (enyne derivatives 1–3) were isolated from the organic extract obtained from the red alga Laurencia obtusa, collected from the Red Sea. The chemical structures of the isolated compounds were established by spectroscopical data analyses. Potent anti-inflammatory effect of the isolated metabolites was evidenced by inhibition of the release of inflammatory mediators (e.g., TNF-α, IL-1β and IL-6) by employing Human Peripheral Blood Mononuclear Cells (PBMC). Full article

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34 pages, 8776 KiB

Open AccessReview

A Review on the Phytochemistry, Medicinal Properties and Pharmacological Activities of 15 Selected Myanmar Medicinal Plants

by Mya Mu Aye, Hnin Thanda Aung, Myint Myint Sein and Chabaco Armijos

Molecules 2019, 24(2), 293; https://doi.org/10.3390/molecules24020293 - 15 Jan 2019

Cited by 108 | Viewed by 11325

Abstract

Medicinal plants are a reservoir of biologically active compounds with therapeutic properties that over time have been reported and used by diverse groups of people for treatment of various diseases. This review covers 15 selected medicinal plants distributed in Myanmar, including Dalbergia cultrata [...] Read more.

Medicinal plants are a reservoir of biologically active compounds with therapeutic properties that over time have been reported and used by diverse groups of people for treatment of various diseases. This review covers 15 selected medicinal plants distributed in Myanmar, including Dalbergia cultrata, Eriosema chinense, Erythrina suberosa, Millettia pendula, Sesbania grandiflora, Tadehagi triquetrum, Andrographis echioides, Barleria cristata, Justicia gendarussa, Premna integrifolia, Vitex trifolia, Acacia pennata, Cassia auriculata, Croton oblongifolius and Glycomis pentaphylla. Investigation of the phytochemical constituents, biological and pharmacological activities of the selected medicinal plants is reported. This study aims at providing a collection of publications on the species of selected medicinal plants in Myanmar along with a critical review of the literature data. As a country, Myanmar appears to be a source of traditional drugs that have not yet been scientifically investigated. This review will be support for further investigations on the pharmacological activity of medicinal plant species in Myanmar. Full article

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10 pages, 639 KiB

Open AccessFeature PaperArticle

Erubescensoic Acid, a New Polyketide and a Xanthonopyrone SPF-3059-26 from the Culture of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA 0220 and Antibacterial Activity Evaluation of Some of Its Constituents

by Decha Kumla, Tida Dethoup, Luís Gales, José A. Pereira, Joana Freitas-Silva, Paulo M. Costa, Artur M. S. Silva, Madalena M. M. Pinto and Anake Kijjoa

Molecules 2019, 24(1), 208; https://doi.org/10.3390/molecules24010208 - 8 Jan 2019

Cited by 19 | Viewed by 4750

Abstract

A new polyketide erubescensoic acid (1), and the previously reported xanthonopyrone, SPF-3059-26 (2), were isolated from the uninvestigated fractions of the ethyl acetate crude extract of the marine sponge-associated fungus Penicillium erubescens KUFA0220. The structures of the new compound, [...] Read more.

A new polyketide erubescensoic acid (1), and the previously reported xanthonopyrone, SPF-3059-26 (2), were isolated from the uninvestigated fractions of the ethyl acetate crude extract of the marine sponge-associated fungus Penicillium erubescens KUFA0220. The structures of the new compound, erubescensoic acid (1), and the previously reported SPF-3059-26 (2), were elucidated by extensive analysis of 1D and 2D-NMR spectra as well as HRMS. The absolute configuration of the stereogenic carbon of erubescensoic acid (1) was determined by X-ray analysis. Erubescensoic acid (1) and SPF-3059-26 (2), together with erubescenschromone B (3), penialidin D (4), and 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromen-5-carboxylic acid (5), recently isolated from this fungus, were assayed for their antibacterial activity against gram-positive and gram-negative reference strains and the multidrug-resistant (MDR) strains from the environment. The capacity of these compounds to interfere with the bacterial biofilm formation and their potential synergism with clinically relevant antibiotics for the MDR strains were also investigated. Full article

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20 pages, 789 KiB

Open AccessArticle

Chemical Eustress Elicits Tailored Responses and Enhances the Functional Quality of Novel Food Perilla frutescens

by Youssef Rouphael, Marios C. Kyriacou, Petronia Carillo, Fabiana Pizzolongo, Raffaele Romano and Maria Isabella Sifola

Molecules 2019, 24(1), 185; https://doi.org/10.3390/molecules24010185 - 6 Jan 2019

Cited by 44 | Viewed by 4893

Abstract

Consumer demand for fresh and functional horticultural products is on the rise. Perilla frutescens, L. Britt (Lamiaceae) is a potential specialty/niche crop for consumption and therapeutic uses with high contents of phenolic and volatile compounds. Plant growth, mineral composition, polyphenol [...] Read more.

Consumer demand for fresh and functional horticultural products is on the rise. Perilla frutescens, L. Britt (Lamiaceae) is a potential specialty/niche crop for consumption and therapeutic uses with high contents of phenolic and volatile compounds. Plant growth, mineral composition, polyphenol profile and aroma volatile components of two perilla genotypes in response to salinity (non-salt control, 10, 20 or 30 mM NaCl) applied as chemical eustressor were assessed. Salinity suppressed growth and yield of both genotypes, although the red-pigmented genotype was less sensitive than the green-pigmented one. Mild (10 mM NaCl) and moderate (20 and 30 mM NaCl) salinity suppressed foliar potassium, magnesium, nitrate and chlorophyll a concentrations of both genotypes and increased the levels of rosmarinic acid, total polyphenols and target aroma volatile components. Green perilla showed higher yield and biomass production and higher content of protein, dry matter, calcium, magnesium, perilla ketone and cis-jasmone, whereas red perilla exhibited higher content of potassium, chlorophyll a, rosmarinic acid, total polyphenols, perilla aldehyde and benzaldehyde. Our findings support that chemical eustressors such as mild to moderate salinity offer valuable means to manipulate phytochemical and aroma profiles. Full article

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2018

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15 pages, 1832 KiB

Open AccessArticle

Identification of Antioxidant Peptides in Enzymatic Hydrolysates of Carp (Cyprinus Carpio) Skin Gelatin

by Joanna Tkaczewska, Michal Bukowski and Paweł Mak

Molecules 2019, 24(1), 97; https://doi.org/10.3390/molecules24010097 - 28 Dec 2018

Cited by 66 | Viewed by 5385

Abstract

The protein by-products from carp (Cyprinus carpio) are normally discarded as industrial waste during fish processing. The objective of this study was to identify and characterise the peptides with a potential antioxidant activity that are released from carp skin proteins during [...] Read more.

The protein by-products from carp (Cyprinus carpio) are normally discarded as industrial waste during fish processing. The objective of this study was to identify and characterise the peptides with a potential antioxidant activity that are released from carp skin proteins during hydrolysis by the Protamex enzyme mixture. This study shows that a hydrolysate of carp skin gelatin and its reversed-phase chromatography fractions have strong in vitro antioxidant properties. Among these fractions, the alanine-tyrosine (Ala-Tyr) dipeptide was identified as the major compound with high antioxidant potential. The peptide has good stability during in vitro enzymatic digestion assay and can inhibit the angiotensin-converting enzyme (ACE). In conclusion, our study proves that both the unfractionated hydrolysate of carp skin gelatin and the above-mentioned Ala-Tyr dipeptide represents attractive novel compounds for the formulation of antioxidant foods. Full article

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10 pages, 1065 KiB

Open AccessArticle

Isolation, Chemical Profile and Antimalarial Activities of Bioactive Compounds from Rauvolfia caffra Sond

by Dorcas B. Tlhapi, Isaiah D. I. Ramaite, Teunis Van Ree, Chinedu P. Anokwuru, Taglialatela-Scafati Orazio and Heinrich C. Hoppe

Molecules 2019, 24(1), 39; https://doi.org/10.3390/molecules24010039 - 21 Dec 2018

Cited by 11 | Viewed by 4318

Abstract

In this study, the chemical profile of a crude methanol extract of Rauvolfia caffra Sond was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Column chromatography and preparative thin layer chromatography were used to isolate three indole alkaloids (raucaffricine, N-methylsarpagine and spegatrine) and [...] Read more.

In this study, the chemical profile of a crude methanol extract of Rauvolfia caffra Sond was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Column chromatography and preparative thin layer chromatography were used to isolate three indole alkaloids (raucaffricine, N-methylsarpagine and spegatrine) and one triterpenoid (lupeol). The antiplasmodial activity was determined using the parasite lactate dehydrogenase (pLDH) assay. The UPLC-MS profile of the crude extract reveals that the major constituents of R. caffra are raucaffricine (m/z 513.2) and spegatrine (m/z 352.2). Fraction 3 displayed the highest antiplasmodial activity with an IC₅₀ of 6.533 μg/mL. However, raucaffricine, isolated from the active fraction did not display any activity. The study identifies the major constituents of R. caffra and also demonstrates that the major constituents do not contribute to the antiplasmodial activity of R. caffra. Full article

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30 pages, 3435 KiB

Open AccessReview

The Potential Use of Plant Natural Products and Plant Extracts with Antioxidant Properties for the Prevention/Treatment of Neurodegenerative Diseases: In Vitro, In Vivo and Clinical Trials

by Franziska Pohl and Paul Kong Thoo Lin

Molecules 2018, 23(12), 3283; https://doi.org/10.3390/molecules23123283 - 11 Dec 2018

Cited by 195 | Viewed by 16059

Abstract

Neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, present a major health issue and financial burden for health care systems around the world. The impact of these diseases will further increase over the next decades due to increasing life expectancies. No [...] Read more.

Neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, present a major health issue and financial burden for health care systems around the world. The impact of these diseases will further increase over the next decades due to increasing life expectancies. No cure is currently available for the treatment of these conditions; only drugs, which merely alleviate the symptoms. Oxidative stress has long been associated with neurodegeneration, whether as a cause or as part of the downstream results caused by other factors. Thus, the use of antioxidants to counter cellular oxidative stress within the nervous system has been suggested as a potential treatment option for neurological disorders. Over the last decade, significant research has focused on the potential use of natural antioxidants to target oxidative stress. However, clinical trial results have lacked success for the treatment of patients with neurological disorders. The knowledge that natural extracts show other positive molecular activities in addition to antioxidant activity, however, has led to further research of natural extracts for their potential use as prevention or treatment/management of neurodegenerative diseases. This review will cover several in vitro and in vivo research studies, as well as clinical trials, and highlight the potential of natural antioxidants. Full article

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14 pages, 1773 KiB

Open AccessArticle

Simultaneous Quantitation of Isoprenoid Pyrophosphates in Plasma and Cancer Cells Using LC-MS/MS

by Yashpal S. Chhonker, Staci L. Haney, Veenu Bala, Sarah A. Holstein and Daryl J. Murry

Molecules 2018, 23(12), 3275; https://doi.org/10.3390/molecules23123275 - 11 Dec 2018

Cited by 19 | Viewed by 6363

Abstract

Isoprenoids (IsoP) are an important class of molecules involved in many different cellular processes including cholesterol synthesis. We have developed a sensitive and specific LC-MS/MS method for the quantitation of three key IsoPs in bio-matrices, geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl [...] Read more.

Isoprenoids (IsoP) are an important class of molecules involved in many different cellular processes including cholesterol synthesis. We have developed a sensitive and specific LC-MS/MS method for the quantitation of three key IsoPs in bio-matrices, geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP). LC-MS/MS analysis was performed using a Nexera UPLC System connected to a LCMS-8060 (Shimadzu Scientific Instruments, Columbia, MD) with a dual ion source. The electrospray ionization source was operated in the negative MRM mode. The chromatographic separation and detection of analytes was achieved on a reversed phase ACCQ-TAG Ultra C18 (1.7 µm, 100 mm × 2.1 mm I.D.) column. The mobile phase consisted of (1) a 10 mM ammonium carbonate with 0.1% ammonium hydroxide in water, and (2) a 0.1% ammonium hydroxide in acetonitrile/methanol (75/25). The flow rate was set to 0.25 mL/min in a gradient condition. The limit of quantification was 0.04 ng/mL for all analytes with a correlation coefficient (r2) of 0.998 or better and a total run time of 12 min. The inter- and intra-day accuracy (85–115%) precision (<15%), and recovery (40–90%) values met the acceptance criteria. The validated method was successfully applied to quantitate basal concentrations of GPP, FPP and GGPP in human plasma and in cultured cancer cell lines. Our LC-MS/MS method may be used for IsoP quantification in different bio-fluids and to further investigate the role of these compounds in various physiological processes. Full article

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14 pages, 3041 KiB

Open AccessArticle

Chemical Characterization and Hypoglycaemic Activities In Vitro of Two Polysaccharides from Inonotus obliquus by Submerged Culture

by Jiao Xue, Shisheng Tong, Zhaorun Wang and Ping Liu

Molecules 2018, 23(12), 3261; https://doi.org/10.3390/molecules23123261 - 10 Dec 2018

Cited by 33 | Viewed by 3941

Abstract

Polysaccharides from the fungus Inonotus obliquus have been found to be biologically active. In this study, we carried out a preliminary characterisation and assessment of the hypoglycaemic activities of the polysaccharides (IOEP) from Inonotus obliquus obtained by liquid fermentation. Two polysaccharides, IOEP1 and [...] Read more.

Polysaccharides from the fungus Inonotus obliquus have been found to be biologically active. In this study, we carried out a preliminary characterisation and assessment of the hypoglycaemic activities of the polysaccharides (IOEP) from Inonotus obliquus obtained by liquid fermentation. Two polysaccharides, IOEP1 and IOEP2, were isolated from IOEP. IOEP1, with a molecular weight of 20 KDa, was mainly composed of galatose and mannose, while IOEP2, with a molecular weight of 200 KDa, was mainly composed of arabinose. Fourier-transform infrared analysis showed that both IOEP1 and IOEP2 were pyran-type polysaccharides. ¹H-NMR spectra showed that the glycosidic bonds of IOEP1 and IOEP2 were both α-type and β-type. In addition, IOEP1 and IOEP2 strongly increased the glucose consumption of HepG2 cells and insulin-resistant HepG2 cells in vitro. These findings provide a theoretical basis that IOEP1 and IOEP2 might be suitable as anti-diabetes agents in functional foods and natural drugs. Full article

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13 pages, 1281 KiB

Open AccessArticle

Crystal Structures and Cytotoxicity of ent-Kaurane-Type Diterpenoids from Two Aspilia Species

by Souaibou Yaouba, Arto Valkonen, Paolo Coghi, Jiaying Gao, Eric M. Guantai, Solomon Derese, Vincent K. W. Wong, Máté Erdélyi and Abiy Yenesew

Molecules 2018, 23(12), 3199; https://doi.org/10.3390/molecules23123199 - 4 Dec 2018

Cited by 8 | Viewed by 7166

Abstract

A phytochemical investigation of the roots of Aspilia pluriseta led to the isolation of ent-kaurane-type diterpenoids and additional phytochemicals (1–23). The structures of the isolated compounds were elucidated based on Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric [...] Read more.

A phytochemical investigation of the roots of Aspilia pluriseta led to the isolation of ent-kaurane-type diterpenoids and additional phytochemicals (1–23). The structures of the isolated compounds were elucidated based on Nuclear Magnetic Resonance (NMR) spectroscopic and mass spectrometric analyses. The absolute configurations of seven of the ent-kaurane-type diterpenoids (3–6, 6b, 7 and 8) were determined by single crystal X-ray diffraction studies. Eleven of the compounds were also isolated from the roots and the aerial parts of Aspilia mossambicensis. The literature NMR assignments for compounds 1 and 5 were revised. In a cytotoxicity assay, 12α-methoxy-ent-kaur-9(11),16-dien-19-oic acid (1) (IC₅₀ = 27.3 ± 1.9 µM) and 9β-hydroxy-15α-angeloyloxy-ent-kaur-16-en-19-oic acid (3) (IC₅₀ = 24.7 ± 2.8 µM) were the most cytotoxic against the hepatocellular carcinoma (Hep-G2) cell line, while 15α-angeloyloxy-16β,17-epoxy-ent-kauran-19-oic acid (5) (IC₅₀ = 30.7 ± 1.7 µM) was the most cytotoxic against adenocarcinomic human alveolar basal epithelial (A549) cells. Full article

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13 pages, 1541 KiB

Open AccessArticle

Anti-Inflammatory, Antioxidant, and Hypolipidemic Effects of Mixed Nuts in Atherogenic Diet-Fed Rats

by Mee Young Hong, Shauna Groven, Amanda Marx, Caitlin Rasmussen and Joshua Beidler

Molecules 2018, 23(12), 3126; https://doi.org/10.3390/molecules23123126 - 29 Nov 2018

Cited by 27 | Viewed by 5565

Abstract

Nut consumption is associated with reduced risk of cardiovascular disease (CVD). Because most studies have administered single nut varieties, it is unknown whether mixed nuts will also reduce CVD risk. The objective of this study was to compare the effects of mixed nut [...] Read more.

Nut consumption is associated with reduced risk of cardiovascular disease (CVD). Because most studies have administered single nut varieties, it is unknown whether mixed nuts will also reduce CVD risk. The objective of this study was to compare the effects of mixed nut and pistachio consumption on lipid profiles, glucose, inflammation, oxidative stress, and antioxidant capacity in rats fed an atherogenic diet. Thirty male Sprague-Dawley rats (21 days old) were assigned into three groups (n = 10) based on initial body weight and fed either an isocaloric control diet (no nuts), 8.1% pistachio diet (single nut), or 7.5% mixed nut diet (almonds, brazil nuts, cashews, macadamia nuts, peanuts, pecans, pistachios, and walnuts) for 8 weeks. Both pistachios and mixed nuts significantly decreased triglycerides, total cholesterol, and LDL-cholesterol (p < 0.05) compared with controls. Both nut groups exhibited reductions in C-reactive protein (p = 0.045) and oxidative stress (p = 0.004). The mixed nut group had greater superoxide dismutase (p = 0.004) and catalase (p = 0.044) and lower aspartate aminotransferase (p = 0.048) activities. Gene expression for Fas, Hmgcr, and Cox2 was downregulated for both nut groups compared to controls (p < 0.05). In conclusion, mixed nuts and individual nut varieties have comparable effects on CVD risk factors in rats. Full article

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13 pages, 1674 KiB

Open AccessArticle

Characterization and Prebiotic Potential of Longan Juice Obtained by Enzymatic Conversion of Constituent Sucrose into Fructo-Oligosaccharides

by Yongxia Cheng, Haibo Lan, Lei Zhao, Kai Wang and Zhuoyan Hu

Molecules 2018, 23(10), 2596; https://doi.org/10.3390/molecules23102596 - 10 Oct 2018

Cited by 22 | Viewed by 4599

Abstract

The prebiotic potential of longan juice obtained by a commercial Viscozyme L for conversion of constituent sucrose to fructo-oligosaccharide was investigated. The physicochemical properties and carbohydrate composition of the longan juice was evaluated before and after enzymatic treatment. The stimulation effects of the [...] Read more.

The prebiotic potential of longan juice obtained by a commercial Viscozyme L for conversion of constituent sucrose to fructo-oligosaccharide was investigated. The physicochemical properties and carbohydrate composition of the longan juice was evaluated before and after enzymatic treatment. The stimulation effects of the treated longan juice on probiotic bacteria growth were also studied in vitro. The results showed that total soluble solids, yield and clarity of longan juice were all significantly improved after enzyme treatment. The water-soluble polysaccharide content, including pectin, was significantly increased. Compared with the natural longan pulp, the enzyme treated juice showed a significant decrease in sucrose content. Substantial fructo-oligosaccharides including 1-kestose and nystose were synthesized after enzyme treatment. The molecular weight distribution and the monosaccharide composition of the water-soluble polysaccharide were significantly changed by enzyme treatment. The treated longan juice and its ethanol-soluble sugar fraction promoted the growth of Streptococus thermophiles, Lactobacillus acidophilus and Lactobacillus delbrueckii, showing a good potential of the treated longan juice for producing functional foods and nutraceuticals. Full article

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11 pages, 1922 KiB

Open AccessArticle

Identification of Anti-Melanogenesis Constituents from Morus alba L. Leaves

by Hong Xu Li, Jung Up Park, Xiang Dong Su, Kyung Tae Kim, Jong Seong Kang, Young Ran Kim, Young Ho Kim and Seo Young Yang

Molecules 2018, 23(10), 2559; https://doi.org/10.3390/molecules23102559 - 8 Oct 2018

Cited by 42 | Viewed by 6432

Abstract

The individual parts of Morus alba L. including root bark, branches, leaves, and fruits are used as a cosmetic ingredient in many Asian countries. This study identified several anti-melanogenesis constituents in a 70% ethanol extract of M. alba leaves. The ethyl acetate fraction [...] Read more.

The individual parts of Morus alba L. including root bark, branches, leaves, and fruits are used as a cosmetic ingredient in many Asian countries. This study identified several anti-melanogenesis constituents in a 70% ethanol extract of M. alba leaves. The ethyl acetate fraction of the initial ethanol extract decreased the activity of tyrosinase, a key enzyme in the synthetic pathway of melanin. Twelve compounds were isolated from this fraction and their structures were identified based on spectroscopic spectra. Then, the authors investigated the anti-melanogenesis effects of the isolated compounds in B16-F10 mouse melanoma cells. Compounds 3 and 8 significantly inhibited not only melanin production but also intracellular tyrosinase activity in alpha-melanocyte-stimulating-hormone (α-MSH)-induced B16-F10 cells in a dose-dependent manner. These same compounds also inhibited melanogenesis-related protein expression such as microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1). Compound 3 modulated the cAMP-responsive element-binding protein (CREB) and p38 signaling pathways in α-MSH-activated B16-F10 melanoma cells, which resulted in the anti-melanogenesis effects. These results suggest that compound 3, isolated from M. alba leaves, could be used to inhibit melanin production via the regulation of melanogenesis-related protein expression. Full article

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19 pages, 1664 KiB

Open AccessArticle

Similarity of Data from Bee Bread with the Same Taxa Collected in India and Romania

by Adriana Cristina Urcan, Adriana Dalila Criste, Daniel Severus Dezmirean, Rodica Mărgăoan, André Caeiro and Maria Graça Campos

Molecules 2018, 23(10), 2491; https://doi.org/10.3390/molecules23102491 - 28 Sep 2018

Cited by 57 | Viewed by 5196

Abstract

Bee Bread samples from Romania and India were analysed by microscopy and High Performance Liquid Chromatography with Diode Array Detection (HPLC/DAD) and compared with pollen from the correspondent taxa. The quantification of sugars, fructose/glucose ratio, total phenolics and flavonoids was also carried out. [...] Read more.

Bee Bread samples from Romania and India were analysed by microscopy and High Performance Liquid Chromatography with Diode Array Detection (HPLC/DAD) and compared with pollen from the correspondent taxa. The quantification of sugars, fructose/glucose ratio, total phenolics and flavonoids was also carried out. From the results was possible to identify Brassica and Eucalyptus samples that present similar HPLC/DAD profiles with the respective ultraviolet (UV) identification of the main compounds as Kaempferol-3-O-glycosides and Hydrocinnamic acid derivatives. The Fructose/Glucose (F/G) ratio and the total amounts of phenolics and flavonoids was in line with the prevalence of the specie identified. These coincident fingerprints gave the identification of the samples, as was previously proposed for bee pollens. This paper relates for the first time the achievement on the taxon carried out previously only for bee pollens. It was reported for the first time that this phenolic profile remains unchanged in the case of floral pollen (hand collected), bee pollen and bee bread. Despite the biochemical transformation that occurs during the fermentation of bee bread, it seems that these phenolic compounds are not affected and remain unchanged. Also, variables such as soil and climate do not seem to influence these compounds for the kind of samples under study. Full article

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18 pages, 4074 KiB

Open AccessArticle

Anti-Inflammatory, Anti-Diabetic, and Anti-Alzheimer’s Effects of Prenylated Flavonoids from Okinawa Propolis: An Investigation by Experimental and Computational Studies

by Md Shahinozzaman, Nozomi Taira, Takahiro Ishii, Mohammad A. Halim, Md Amzad Hossain and Shinkichi Tawata

Molecules 2018, 23(10), 2479; https://doi.org/10.3390/molecules23102479 - 27 Sep 2018

Cited by 74 | Viewed by 8327

Abstract

Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on Caenorhabditis elegans through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated flavonoids from OP, nymphaeol-A (NA), nymphaeol-B (NB), nymphaeol-C (NC), isonymphaeol-B (INB), [...] Read more.

Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on Caenorhabditis elegans through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated flavonoids from OP, nymphaeol-A (NA), nymphaeol-B (NB), nymphaeol-C (NC), isonymphaeol-B (INB), and 3′-geranyl-naringenin (GN), were evaluated for their anti-inflammatory, anti-diabetic, and anti-Alzheimer’s effects using in vitro techniques. They showed significant anti-inflammatory effects through inhibition of albumin denaturation (half maximal inhibitory concentration (IC₅₀) values of 0.26–1.02 µM), nitrite accumulation (IC₅₀ values of 2.4–7.0 µM), and cyclooxygenase-2 (COX-2) activity (IC₅₀ values of 11.74–24.03 µM). They also strongly suppressed in vitro α-glucosidase enzyme activity with IC₅₀ values of 3.77–5.66 µM. However, only INB and NA inhibited acetylcholinesterase significantly compared to the standard drug donepezil, with IC₅₀ values of 7.23 and 7.77 µM, respectively. Molecular docking results indicated that OP compounds have good binding affinity to the α-glucosidase and acetylcholinesterase proteins, making non-bonded interactions with their active residues and surrounding allosteric residues. In addition, none of the compounds violated Lipinski’s rule of five and showed notable toxicity parameters. Density functional theory (DFT)-based global reactivity descriptors demonstrated their high reactive nature along with the kinetic stability. In conclusion, this combined study suggests that OP components might be beneficial in the treatment of inflammation, type 2 diabetes mellitus, and Alzheimer’s disease. Full article

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11 pages, 744 KiB

Open AccessArticle

Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

by Grażyna Budryn, Joanna Grzelczyk and Horacio Pérez-Sánchez

Molecules 2018, 23(10), 2471; https://doi.org/10.3390/molecules23102471 - 26 Sep 2018

Cited by 15 | Viewed by 4016

Abstract

Actin functions are crucial for the ability of the cell to execute dynamic cytoskeleton reorganization and movement. Nutraceuticals that form complexes with actin and reduce its polymerization can be used in cancer therapy to prevent cell migration and metastasis of tumors. The aim [...] Read more.

Actin functions are crucial for the ability of the cell to execute dynamic cytoskeleton reorganization and movement. Nutraceuticals that form complexes with actin and reduce its polymerization can be used in cancer therapy to prevent cell migration and metastasis of tumors. The aim of this study was to evaluate the ability of isoflavones to form complexes with actin. Docking simulation and isothermal titration calorimetry were used for this purpose. The formation of complexes by hydrogen bonds, hydrophobic and π-π interactions was demonstrated. Interactions occurred at the ATP binding site, which may limit the rotation of the actin molecule observed during polymerization and also at the site responsible for contacts during polymerization, reducing the ability of the molecule to form filaments. The greatest therapeutic potential was demonstrated by isoflavones occurring in red clover sprouts, i.e., biochanin A and formononetin, being methoxy derivatives of genistein and daidzein. Full article

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7 pages, 572 KiB

Open AccessArticle

Daphnauranins C–E, Three New Antifeedants from Daphne aurantiaca Roots

by Sheng Zhuo Huang, Qing Yun Ma, Qi Wang, Hao Fu Dai, Yu Qing Liu, Jun Zhou and You Xing Zhao

Molecules 2018, 23(10), 2429; https://doi.org/10.3390/molecules23102429 - 21 Sep 2018

Cited by 6 | Viewed by 3407

Abstract

Daphnauranins C–E (compounds 1–3), two sesquiterpenoids and one monoterpenoid were isolated from the roots of Daphne aurantiaca Diels. Daphnauranin C is a 9-O-13 etherified and hydroperoxy-substituted guaiane sesquiterpenoid, daphnauranin D is a guaiane sesquiterpenoid ketal, and daphnauranin E [...] Read more.

Daphnauranins C–E (compounds 1–3), two sesquiterpenoids and one monoterpenoid were isolated from the roots of Daphne aurantiaca Diels. Daphnauranin C is a 9-O-13 etherified and hydroperoxy-substituted guaiane sesquiterpenoid, daphnauranin D is a guaiane sesquiterpenoid ketal, and daphnauranin E is a monoterpenoid lactone. Their structures were elucidated by comprehensive analyses of MS, 1D NMR, and 2D NMR spectroscopic data. In an anti-feeding activities test, daphnauranins C–E showed activity against male fruit fly with anti-feeding indexes (AI) up to 39.1, 39.2, and 27.8% respectively, at 1 mM. Full article

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21 pages, 4402 KiB

Open AccessFeature PaperArticle

Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety in Rat by Fingerprint-Efficacy Study

by Shao-Nan Wang, Yong-Sheng Ding, Xiao-Jie Ma, Cheng-Bowen Zhao, Ming-Xuan Lin, Jing Luo, Yi-Nan Jiang, Shuai He, Jian-You Guo and Jin-Li Shi

Molecules 2018, 23(9), 2329; https://doi.org/10.3390/molecules23092329 - 12 Sep 2018

Cited by 19 | Viewed by 4920

Abstract

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to [...] Read more.

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat’s plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat’s cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM. Full article

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16 pages, 1191 KiB

Open AccessArticle

Phenolic Composition Stability and Antioxidant Activity of Sour Cherry Liqueurs

by Anna Sokół-Łętowska, Alicja Z. Kucharska, Antoni Szumny, Katarzyna Wińska and Agnieszka Nawirska-Olszańska

Molecules 2018, 23(9), 2156; https://doi.org/10.3390/molecules23092156 - 27 Aug 2018

Cited by 15 | Viewed by 4130

Abstract

The aim of the study was to evaluate changes of phenolic and anthocyanin contents, antioxidant activity, aroma compounds and color of sour cherry liqueurs with and without sugar during 6 months of storage at temperatures of 15 °C and 30 °C. Contents of [...] Read more.

The aim of the study was to evaluate changes of phenolic and anthocyanin contents, antioxidant activity, aroma compounds and color of sour cherry liqueurs with and without sugar during 6 months of storage at temperatures of 15 °C and 30 °C. Contents of phenolic compounds (HPLC, UPLC-MS) and antiradical activity (ABTS) changes were measured. Color changes were measured by an objective method (ColorQuest XE). During storage fluctuations of phenolic compounds and antioxidant activity content were observed. The content of substances which react with Folin-Ciocalteu reagent was comparable before and after 24 weeks. During the 24 weeks of storage, the highest average antioxidant activity against ABTS radicals was shown by sour cherry liqueurs without sugar, stored at 15 °C. Quicker degradation of anthocyanins was observed in liqueurs without sugar, stored at 30 °C (t_1/2—5.9 weeks in liqueurs with sugar and 6.6 weeks in liqueurs without sugar). Better stability of red color was observed in liqueurs with sugar, stored at 15 °C. The content of the dominant aroma compound, benzaldehyde, increased during storage. Long-term storage and sugar addition decreases color attributes but increases organoleptic value without of great influence on antioxidant activity. Studies on a half-year period of liqueur storage showed that their characteristic features are almost unchanged if stored at 15 °C and without sugar added, but organoleptic properties were better in samples stored at 30 °C. Full article

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9 pages, 803 KiB

Open AccessArticle

New Naphthalene Derivatives from the Bulbs of Eleutherine americana with Their Protective Effect on the Injury of HUVECs

by De-Li Chen, Mei-Geng Hu, Yang-Yang Liu, Rong-Tao Li, Meng Yu, Xu-Dong Xu and Guo-Xu Ma

Molecules 2018, 23(9), 2111; https://doi.org/10.3390/molecules23092111 - 22 Aug 2018

Cited by 11 | Viewed by 4376

Abstract

Five new naphthalene derivatives, named Eleutherols A–C (1–3) and Eleuthinones B–C (4,5), together with three known compounds were isolated from the bulbs of Eleutherine americana. Their structures were elucidated on the basis of spectroscopic [...] Read more.

Five new naphthalene derivatives, named Eleutherols A–C (1–3) and Eleuthinones B–C (4,5), together with three known compounds were isolated from the bulbs of Eleutherine americana. Their structures were elucidated on the basis of spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR techniques. These compounds exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro. Full article

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12 pages, 770 KiB

Open AccessArticle

Phenolic Compounds and Bioactivity of Cytisus villosus Pourr.

by Amel Bouziane, Boulanouar Bakchiche, Maria Inês Dias, Lillian Barros, Isabel C.F.R. Ferreira, Husam A. AlSalamat and Sanaa K. Bardaweel

Molecules 2018, 23(8), 1994; https://doi.org/10.3390/molecules23081994 - 10 Aug 2018

Cited by 18 | Viewed by 7113

Abstract

The present study focuses on the chemical composition, antioxidant, antimicrobial, and antiproliferative activities of the ethyl acetate and aqueous extracts obtained from the aerial parts of Cytisus villosus Pourr. HPLC-DAD-ESI/MSn was used to identify the phenolic compounds, being (epi)gallocatechin dimer the major compound [...] Read more.

The present study focuses on the chemical composition, antioxidant, antimicrobial, and antiproliferative activities of the ethyl acetate and aqueous extracts obtained from the aerial parts of Cytisus villosus Pourr. HPLC-DAD-ESI/MSn was used to identify the phenolic compounds, being (epi)gallocatechin dimer the major compound (111 ± 5 µg/g·dw) in the aqueous extract, while myricetin-O-rhamnoside (226 ± 9 µg/g·dw) was the main molecule in the ethyl acetate extract. Both extracts exhibited good scavenging activities against DPPH radical (EC₅₀ µg/mL of 59 ± 2 and 31 ± 2 for aqueous and ethyl acetate extracts, respectively). However, the ethyl acetate extract demonstrated more potent quenching activities than the aqueous extract. The antimicrobial activities were assessed on selected Gram-positive (Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, as well as on pathogenic fungus Candida glabrata. The extracts possessed selective and potent antimicrobial activities against the Gram-positive bacterium (IC₅₀ of 186 ± 9 μg/mL and 92 ± 3 μg/mL for aqueous and ethyl acetate extracts, respectively). Finally, C. villosus extracts were evaluated for their antiproliferative potential on three human cancer cell lines representing breast and colon cancers. Although both extracts demonstrated sufficient growth inhibition of the three different cell lines, the ethyl acetate extract exhibited higher activity (LD₅₀ values of 1.57 ± 0.06 mg/mL, 2.2 ± 0.1 mg/mL, and 3.2 ± 0.2 mg/mL for T47D, MCF-7, and HCT-116 cell lines). Both the extracts obtained from the aerial parts of C. villosus revealed very promising results and could be applied as functional agents in the food, pharmaceutical, and cosmeceutical industries. Full article

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11 pages, 825 KiB

Open AccessArticle

The Substituent Effect on the Radical Scavenging Activity of Apigenin

by Yan-Zhen Zheng, Da-Fu Chen, Geng Deng and Rui Guo

Molecules 2018, 23(8), 1989; https://doi.org/10.3390/molecules23081989 - 10 Aug 2018

Cited by 23 | Viewed by 4796

Abstract

Flavonoids widely found in natural foods are excellent free radical scavengers. The relationship between the substituent and antioxidative activity of flavonoids has not yet been completely elucidated. In this work, the antioxidative activity of apigenin derivatives with different substituents at the C3 position [...] Read more.

Flavonoids widely found in natural foods are excellent free radical scavengers. The relationship between the substituent and antioxidative activity of flavonoids has not yet been completely elucidated. In this work, the antioxidative activity of apigenin derivatives with different substituents at the C3 position was determined by density functional theory (DFT) calculations. The bond dissociation enthalpy (BDE), ionization potential (IP), and proton affinity (PA) were calculated. Donator acceptor map (DAM) analysis illustrated that the studied compounds are worse electron acceptors than F and also are not better electron donors than Na. The strongest antioxidative group of apigenin derivatives was the same as apigenin. Excellent correlations were found between the BDE/IP/PA and Hammett sigma constants. Therefore, Hammett sigma constants can be used to predict the antioxidative activity of substituted apigenin and to design new antioxidants based on flavonoids. In non-polar phases, the antioxidative activity of apigenin was increased by the electron-withdrawing groups, while it was reduced by the electron-donating groups. Contrary results occurred in the polar phase. The electronic effect of the substituents on BDE(4′-OH), BDE(5-OH), PA(4′-OH), and IP is mainly controlled by the resonance effect, while that on BDE(7-OH), PA(5-OH), and PA(7-OH) is governed by the field/inductive effect. Full article

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15 pages, 2568 KiB

Open AccessArticle

Physicochemical Characterization, Antioxidant and Immunostimulatory Activities of Sulfated Polysaccharides Extracted from Ascophyllum nodosum

by Ligen Chen, Yan Wang, Hui Yang, Han Li, Wei Xu, Guijie Chen and Hongjun Zhu

Molecules 2018, 23(8), 1912; https://doi.org/10.3390/molecules23081912 - 31 Jul 2018

Cited by 22 | Viewed by 4375

Abstract

Polysaccharides from Ascophyllum nodosum (AnPS) were extracted and purified via an optimized protocol. The optimal extraction conditions were as follows: extraction time of 4.3 h, extraction temperature of 84 °C and ratio (v/w, mL/g) of extraction solvent (water) to [...] Read more.

Polysaccharides from Ascophyllum nodosum (AnPS) were extracted and purified via an optimized protocol. The optimal extraction conditions were as follows: extraction time of 4.3 h, extraction temperature of 84 °C and ratio (v/w, mL/g) of extraction solvent (water) to raw material of 27. The resulting yield was 9.15 ± 0.23% of crude AnPS. Two fractions, named AnP1-1 and AnP2-1 with molecular weights of 165.92 KDa and 370.68 KDa, were separated from the crude AnPS by chromatography in DEAE Sepharose Fast Flow and Sephacryl S-300, respectively. AnP1-1 was composed of mannose, ribose, glucuronic acid, glucose and fucose, and AnP2-1 was composed of mannose, glucuronic acid, galactose and fucose. AnPS, AnP1-1 and AnP2-1 exhibited high scavenging activities against ABTS radical and superoxide radical, and showed protective effect on H₂O₂-induced oxidative injury in RAW264.7 cells. Furthermore, the immunostimulatory activities of AnP1-1 and AnP2-1 were evaluated by Caco-2 cells, the results showed both AnP1-1 and AnP2-1 could significantly promote the production of immune reactive molecules such as interleukin (IL)-8, IL-1β, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Therefore, the results suggest that AnPS and its two fractions may be explored as a potential functional food supplement. Full article

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12 pages, 1560 KiB

Open AccessArticle

Effects of Linalyl Acetate on Thymic Stromal Lymphopoietin Production in Mast Cells

by Phil-Dong Moon, Na-Ra Han, Jin Soo Lee, Hyung-Min Kim and Hyun-Ja Jeong

Molecules 2018, 23(7), 1711; https://doi.org/10.3390/molecules23071711 - 13 Jul 2018

Cited by 17 | Viewed by 4871

Abstract

Thymic stromal lymphopoietin (TSLP) is an important factor responsible for the pathogenesis of allergic diseases, such as atopic dermatitis and asthma. Because linalyl acetate (LA) possesses a wide range of pharmacological properties, being antispasmodic, anti-inflammatory, and anti-hyperpigmentation, we hypothesized that LA could inhibit [...] Read more.

Thymic stromal lymphopoietin (TSLP) is an important factor responsible for the pathogenesis of allergic diseases, such as atopic dermatitis and asthma. Because linalyl acetate (LA) possesses a wide range of pharmacological properties, being antispasmodic, anti-inflammatory, and anti-hyperpigmentation, we hypothesized that LA could inhibit TSLP. Therefore, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, Western blot analysis, fluorescent analyses of the intracellular calcium levels, and the phorbol myristate acetate (PMA)-induced edema model were used to investigate how LA inhibits the production of TSLP in HMC-1 cells. LA reduced the production and mRNA expression of TSLP in HMC-1 cells. LA also inhibited the activation of nuclear factor-κB and degradation of IκBα. PMA plus A23187 stimulation up-regulated caspase-1 activity in HMC-1 cells; however, this up-regulated caspase-1 activity was down-regulated by LA. Finally, LA decreased intracellular calcium levels in HMC-1 cells as well as PMA-induced ear swelling responses in mice. Taken together, these results suggest that LA would be beneficial to treatment of atopic and inflammatory diseases by reducing TSLP. Full article

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8 pages, 1272 KiB

Open AccessCommunication

Magnolol Inhibits Osteoclast Differentiation via Suppression of RANKL Expression

by Youn-Hwan Hwang, Taesoo Kim, Rajeong Kim and Hyunil Ha

Molecules 2018, 23(7), 1598; https://doi.org/10.3390/molecules23071598 - 2 Jul 2018

Cited by 16 | Viewed by 3893

Abstract

Magnolol, a compound from the traditional Korean herb Magnolia sp., has been exhaustively investigated as a therapeutic agent against several diseases including systemic and local inflammation. We examined the effects of magnolol on osteoclastic differentiation associated with inflammation. Magnolol markedly reduced interleukin (IL)-1-induced [...] Read more.

Magnolol, a compound from the traditional Korean herb Magnolia sp., has been exhaustively investigated as a therapeutic agent against several diseases including systemic and local inflammation. We examined the effects of magnolol on osteoclastic differentiation associated with inflammation. Magnolol markedly reduced interleukin (IL)-1-induced osteoclast formation in co-cultures of murine osteoblasts and bone marrow cells, whereas it had no effect on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in bone marrow macrophage cultures. In osteoblasts, magnolol markedly inhibited both the up-regulation of RANKL expression and the production of prostaglandin E₂ (PGE₂) in response to IL-1 treatment. Addition of exogenous PGE₂ reversed the inhibitory effects of magnolol on IL-1-induced RANKL expression in osteoblasts and osteoclast formation in co-cultures. Magnolol inhibited IL-1-induced PGE₂ production, at least in part by suppressing cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that magnolol inhibits IL-1-induced RANKL expression in osteoblasts through suppression of COX-2 expression and PGE₂ production, resulting in inhibition of osteoclast differentiation in co-cultures. Full article

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41 pages, 1992 KiB

Open AccessReview

Cosmetics Preservation: A Review on Present Strategies

by Noureddine Halla, Isabel P. Fernandes, Sandrina A. Heleno, Patrícia Costa, Zahia Boucherit-Otmani, Kebir Boucherit, Alírio E. Rodrigues, Isabel C. F. R. Ferreira and Maria Filomena Barreiro

Molecules 2018, 23(7), 1571; https://doi.org/10.3390/molecules23071571 - 28 Jun 2018

Cited by 217 | Viewed by 36776

Abstract

Cosmetics, like any product containing water and organic/inorganic compounds, require preservation against microbial contamination to guarantee consumer’s safety and to increase their shelf-life. The microbiological safety has as main goal of consumer protection against potentially pathogenic microorganisms, together with the product’s preservation resulting [...] Read more.

Cosmetics, like any product containing water and organic/inorganic compounds, require preservation against microbial contamination to guarantee consumer’s safety and to increase their shelf-life. The microbiological safety has as main goal of consumer protection against potentially pathogenic microorganisms, together with the product’s preservation resulting from biological and physicochemical deterioration. This is ensured by chemical, physical, or physicochemical strategies. The most common strategy is based on the application of antimicrobial agents, either by using synthetic or natural compounds, or even multifunctional ingredients. Current validation of a preservation system follow the application of good manufacturing practices (GMPs), the control of the raw material, and the verification of the preservative effect by suitable methodologies, including the challenge test. Among the preservatives described in the positive lists of regulations, there are parabens, isothiasolinone, organic acids, formaldehyde releasers, triclosan, and chlorhexidine. These chemical agents have different mechanisms of antimicrobial action, depending on their chemical structure and functional group’s reactivity. Preservatives act on several cell targets; however, they might present toxic effects to the consumer. Indeed, their use at high concentrations is more effective from the preservation viewpoint being, however, toxic for the consumer, whereas at low concentrations microbial resistance can develop. Full article

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14 pages, 608 KiB

Open AccessArticle

(−)-Epicatechin Reduces Blood Pressure and Improves Left Ventricular Function and Compliance in Deoxycorticosterone Acetate-Salt Hypertensive Rats

by Douglas Jackson, Kylie Connolly, Romeo Batacan, Kimberly Ryan, Rebecca Vella and Andrew Fenning

Molecules 2018, 23(7), 1511; https://doi.org/10.3390/molecules23071511 - 22 Jun 2018

Cited by 16 | Viewed by 4427

Abstract

(−)-Epicatechin (E) is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-

α

)-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS) activation and inhibit NADPH oxidase. This study investigated [...] Read more.

(−)-Epicatechin (E) is a flavanol found in green tea and cocoa and has been shown to attenuate tumour necrosis factor alpha (TNF-

α

)-mediated inflammation, improve nitric oxide levels, promote endothelial nitric oxide synthase (eNOS) activation and inhibit NADPH oxidase. This study investigated the effect of 28 days of low epicatechin dosing (1 mg/kg/day) on the cardiovascular function of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Wistar rats (n = 120, 8 weeks of age) underwent uninephrectomy and were randomised into four groups (uninephrectomy (UNX), UNX + E, DOCA, DOCA + E). DOCA and DOCA + E rats received 1% NaCl drinking water along with subcutaneous injections of 25 mg deoxycorticosterone-acetate (in 0.4 mL of dimethylformamide) every fourth day. UNX + E and DOCA + E rats received 1 mg/kg/day of epicatechin by oral gavage. Single-cell micro-electrode electrophysiology, Langendorff isolated-heart assessment and isolated aorta and mesenteric organ baths were used to assess cardiovascular parameters. Serum malondialdehyde concentration was used as a marker of oxidative stress. Myocardial stiffness was increased and left ventricular compliance significantly diminished in the DOCA control group, and these changes were attenuated by epicatechin treatment (p < 0.05). Additionally, the DOCA + E rats showed significantly reduced blood pressure and malondialdehyde concentrations; however, there was no improvement in left ventricular hypertrophy, electrophysiology or vascular function. This study demonstrates the ability of epicatechin to reduce blood pressure, prevent myocardial stiffening and preserve cardiac compliance in hypertrophied DOCA-salt rat hearts. Full article

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14 pages, 1457 KiB

Open AccessArticle

Pentacyclic Triterpenes from Cecropia telenitida Can Function as Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

by Catalina Mosquera, Aram J. Panay and Guillermo Montoya

Molecules 2018, 23(6), 1444; https://doi.org/10.3390/molecules23061444 - 14 Jun 2018

Cited by 10 | Viewed by 5885

Abstract

Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. [...] Read more.

Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. The pharmacological target of these molecules, however, remains unknown. Several lines of evidence indicate that pentacyclic triterpenes inhibit the 11β-hydroxysteroid dehydrogenase type 1 enzyme, which highlights the potential use of this type of natural product as phytotherapeutic or botanical dietary supplements. The main goal of the study was the evaluation of the inhibitory effect of Cecropia telenitida molecules on 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. A pre-fractionated chemical library was obtained from the roots of Cecropia telenitida using several automated chromatography separation steps and a homogeneous time resolved fluorescence assay was used for the bio-guided isolation of inhibiting molecules. The screening of a chemical library consisting of 125 chemical purified fractions obtained from Cecropia telenitida roots identified one fraction displaying 82% inhibition of the formation of cortisol by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Furthermore, a molecule displaying IC₅₀ of 0.95 ± 0.09 µM was isolated from this purified fraction and structurally characterized, which confirms that a pentacyclic triterpene scaffold was responsible for the observed inhibition. Our results support the hypothesis that pentacyclic triterpene molecules from Cecropia telenitida can inhibit 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. These findings highlight the potential ethnopharmacological use of plants from the genus Cecropia for the treatment of metabolic disorders and diabetes. Full article

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10 pages, 1229 KiB

Open AccessArticle

Sterepinic Acids A–C, New Carboxylic Acids Produced by a Marine Alga-Derived Fungus

by Takeshi Yamada, Miwa Matsuda, Mayuko Seki, Megumi Hirose and Takashi Kikuchi

Molecules 2018, 23(6), 1336; https://doi.org/10.3390/molecules23061336 - 1 Jun 2018

Cited by 6 | Viewed by 4783

Abstract

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was [...] Read more.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines. Full article

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10 pages, 1077 KiB

Open AccessArticle

Aspergoterpenins A–D: Four New Antimicrobial Bisabolane Sesquiterpenoid Derivatives from an Endophytic Fungus Aspergillus versicolor

by Zhi-Yong Guo, Ming-Hui Tan, Cheng-Xiong Liu, Meng-Meng Lv, Zhang-Shuang Deng, Fei Cao, Kun Zou and Peter Proksch

Molecules 2018, 23(6), 1291; https://doi.org/10.3390/molecules23061291 - 28 May 2018

Cited by 31 | Viewed by 5197

Abstract

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their [...] Read more.

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A (1) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1–12 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1–12 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL. Full article

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9 pages, 936 KiB

Open AccessArticle

Four New Lignans from Kadsura Interior and Their Bioactivity

by Jiu-Shi Liu, Jin Zhang, Yao-Dong Qi, Xiao-Guang Jia, Ben-Gang Zhang and Hai-Tao Liu

Molecules 2018, 23(6), 1279; https://doi.org/10.3390/molecules23061279 - 26 May 2018

Cited by 4 | Viewed by 3664

Abstract

A phytochemical investigation of the stems of Kadsura interior has led to an isolation of four new lignans, named kadsutherin E–H (1–4), together with two known lignans (5–6). The structures of the four new compounds [...] Read more.

A phytochemical investigation of the stems of Kadsura interior has led to an isolation of four new lignans, named kadsutherin E–H (1–4), together with two known lignans (5–6). The structures of the four new compounds were established on the basis of comprehensive spectroscopic analyses. Compounds 1–6 exhibited inhibition against adenosine diphosphate (ADP) induced platelet aggregation. Among the isolated compounds, kadsutherin F (2) showed the strongest anti-platelet aggregation activity with an inhibition of 49.47%. Full article

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8 pages, 916 KiB

Open AccessFeature PaperCommunication

Antioxidants from the Brown Alga Dictyopteris undulata

by Momochika Kumagai, Keisuke Nishikawa, Hiroshi Matsuura, Taiki Umezawa, Fuyuhiko Matsuda and Tatsufumi Okino

Molecules 2018, 23(5), 1214; https://doi.org/10.3390/molecules23051214 - 18 May 2018

Cited by 16 | Viewed by 5495

Abstract

An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute [...] Read more.

An investigation of anti-oxidative compounds from the brown alga Dictyopteris undulata has led to the isolation and identification of isozonarol, isozonarone, chromazonarol, zonaroic acid and isozonaroic acid. Their structures were identified by comparison of MS and NMR spectra. Full NMR assignment and absolute configuration of isozonaroic acid are described. Isozonarol showed the most potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity among the compounds isolated. Full article

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23 pages, 1164 KiB

Open AccessReview

Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders

by Jingjing Liu, Lingling Yang, Yanhong Dong, Bo Zhang and Xueqin Ma

Molecules 2018, 23(5), 1213; https://doi.org/10.3390/molecules23051213 - 18 May 2018

Cited by 68 | Viewed by 7589

Abstract

Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of [...] Read more.

Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson’s and Alzheimer’s diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials. Thus, it remains unresolved as to whether scientific research can reasonably make use of this natural compound. A systematic summary and knowledge of future prospects are necessary to facilitate further studies for this natural product. The present review generalizes and analyzes the current knowledge on ECH, including its broad distribution, different preparation technologies, poor pharmacokinetics and kinds of therapeutic uses, and the future perspectives of its potential application. Full article

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12 pages, 524 KiB

Open AccessArticle

Identification of Insecticidal Constituents from the Essential Oil from the Aerial Parts Stachys riederi var. japonica

by Meirong Quan, Qi Zhi Liu and Zhi Long Liu

Molecules 2018, 23(5), 1200; https://doi.org/10.3390/molecules23051200 - 17 May 2018

Cited by 23 | Viewed by 4523

Abstract

The essential oil of Stachys riederi var. japonica (Family: Lamiaceae) was extracted by hydrodistillation and determined by GC and GC-MS. A total of 40 components were identified, representing 96.01% of the total oil composition. The major compounds in the essential oil were acetanisole [...] Read more.

The essential oil of Stachys riederi var. japonica (Family: Lamiaceae) was extracted by hydrodistillation and determined by GC and GC-MS. A total of 40 components were identified, representing 96.01% of the total oil composition. The major compounds in the essential oil were acetanisole (15.43%), anisole (9.43%), 1,8-cineole (8.07%), geraniol (7.89%), eugenol (4.54%), caryophyllene oxide (4.47%), caryophyllene (4.21%) and linalool (4.07%). Five active constituents (acetanisole, anisole, 1,8-cineole, eugenol and geraniol) were identified by bioactivity-directed fractionation. The essential oil possessed fumigant toxicity against maize weevils (Sitophilus zeamais) and booklice (Liposcelis bostrychophila), with LC₅₀ values of 15.0 mg/L and 0.7 mg/L, respectively. Eugenol and anisole exhibited stronger fumigant toxicity than the oil against booklice. 1,8-Cineole showed stronger toxicity, and anisole as well as eugenol exhibited the same level of fumigant toxicity as the essential oil against maize weevils. The essential oil also exhibited contact toxicity against S. zeamais adults and L. bostrychophila, with LC₅₀ values of 21.8 µg/adult and 287.0 µg/cm², respectively. The results indicated that the essential oil of S. riederi var. japonica and its isolates show potential as fumigants, and for their contact toxicity against grain storage insects. Full article

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7 pages, 892 KiB

Open AccessArticle

Pyrrole Alkaloids from the Edible Mushroom Phlebopus portentosus with Their Bioactive Activities

by Zhaocui Sun, Meigeng Hu, Zhonghao Sun, Nailiang Zhu, Junshan Yang, Guoxu Ma and Xudong Xu

Molecules 2018, 23(5), 1198; https://doi.org/10.3390/molecules23051198 - 17 May 2018

Cited by 27 | Viewed by 4651

Abstract

Seven pyrrole alkaloids, three of which are novel (phlebopines A–C (1–3)), were isolated from the fruiting bodies of the edible mushroom Phlebopus portentosus. Their structures were determined on the basis of spectroscopic data. All the isolated compounds were [...] Read more.

Seven pyrrole alkaloids, three of which are novel (phlebopines A–C (1–3)), were isolated from the fruiting bodies of the edible mushroom Phlebopus portentosus. Their structures were determined on the basis of spectroscopic data. All the isolated compounds were tested for their neuroprotective properties and acetylcholine esterase (AChE) inhibition activities. Compound 7 displayed remarkable neuroprotective effects against hydrogen peroxide (H₂O₂)-induced neuronal-cell damage in human neuroblastoma SH-SY5Y cells. Full article

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10 pages, 600 KiB

Open AccessArticle

Study on the Polar Extracts of Dendrobium nobile, D. officinale, D. loddigesii, and Flickingeria fimbriata: Metabolite Identification, Content Evaluation, and Bioactivity Assay

by Huiping Chen, Xuewen Li, Yongli Xu, Kakei Lo, Huizhen Zheng, Haiyan Hu, Jun Wang and Yongcheng Lin

Molecules 2018, 23(5), 1185; https://doi.org/10.3390/molecules23051185 - 15 May 2018

Cited by 29 | Viewed by 5370

Abstract

The polar extract of the Dendrobium species or F. fimbriata (a substitute of Dendrobium), between the fat-soluble extract and polysaccharide has barely been researched. This report worked on the qualitative and quantitative studies of polar extracts from D. nobile, D. officinale [...] Read more.

The polar extract of the Dendrobium species or F. fimbriata (a substitute of Dendrobium), between the fat-soluble extract and polysaccharide has barely been researched. This report worked on the qualitative and quantitative studies of polar extracts from D. nobile, D. officinale, D. loddigesii, and F. fimbriata. Eight water-soluble metabolites containing a new diglucoside, flifimdioside A (1), and a rare imidazolium-type alkaloid, anosmine (4), were identified using chromatography as well as spectroscopic techniques. Their contents in the four herbs were high, approximately 0.9–3.7 mg/g based on the analysis of quantitative nuclear magnetic resonance (qNMR) spectroscopy. Biological activity evaluation showed that the polar extract of F. fimbriata or its pure component had good antioxidant and neuroprotective activity; compounds 1‒4 and shihunine (8) showed weak α-glucosidase inhibitory activity; 4 and 8 had weak anti-inflammatory activity. Under trial conditions, all samples had no cytotoxic activity. Full article

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11 pages, 1708 KiB

Open AccessArticle

Pterostilbene and 4′-Methoxyresveratrol Inhibited Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages

by Yun Yao, Kehai Liu, Yueliang Zhao, Xiaoqian Hu and Mingfu Wang

Molecules 2018, 23(5), 1148; https://doi.org/10.3390/molecules23051148 - 11 May 2018

Cited by 27 | Viewed by 5665

Abstract

Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA [...] Read more.

Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA expression. Moreover, both of them inhibited LPS-induced mRNA expression of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and IL-1β, and tumor necrosis factor α (TNF-α), and attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 phosphorylation. In addition, 4MR but not Pte inhibited LPS-induced the activator protein (AP)-1 pathway in RAW 264.7 macrophages. Further study suggested that Pte had an inhibitory effect on extracellular regulated protein kinases (ERK) and p38 activation, but not on c-Jun N-terminal kinase (JNK), while 4MR had an inhibitory effect on JNK and p38 activation, but not on ERK. Taken together, our data suggested that Pte induced anti-inflammatory activity by blocking mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, while 4MR showed anti-inflammatory activity through suppression of MAPK, AP-1, and NF-κB signaling pathways in LPS-treated RAW 264.7 macrophages. Full article

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9 pages, 1575 KiB

Open AccessArticle

Three New Highly Oxygenated Germacranolides from Carpesium Divaricatum and Their Cytotoxic Activity

by Tao Zhang, Jin-Guang Si, Qiu-Bo Zhang, Jia-Huan Chen, Gang Ding, Hong-Wu Zhang, Hong-Mei Jia and Zhong-Mei Zou

Molecules 2018, 23(5), 1078; https://doi.org/10.3390/molecules23051078 - 3 May 2018

Cited by 10 | Viewed by 3935

Abstract

Three new highly oxygenated (2–4), and two known (1 and 5) germacranolides, were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic [...] Read more.

Three new highly oxygenated (2–4), and two known (1 and 5) germacranolides, were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by detailed spectroscopic analysis. The absolute configuration of 1 was established using the circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2–4 were determined using similar CD spectra with 1. The new compound 2 and the known compound 5 exhibited potent cytotoxicity against hepatocellular cancer (Hep G2) and human cervical cancer (HeLa) cells, superior to those of the positive control cis-platin. Full article

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19 pages, 892 KiB

Open AccessFeature PaperArticle

Phenolic Composition and Bioactivity of Lavandula pedunculata (Mill.) Cav. Samples from Different Geographical Origin

by Catarina L. Lopes, Eliana Pereira, Marina Soković, Ana Maria Carvalho, Ana Maria Barata, Violeta Lopes, Filomena Rocha, Ricardo C. Calhelha, Lillian Barros and Isabel C.F.R. Ferreira

Molecules 2018, 23(5), 1037; https://doi.org/10.3390/molecules23051037 - 28 Apr 2018

Cited by 58 | Viewed by 6166

Abstract

The aim of this study was to characterize the phenolic composition and evaluate the bioactivity of several samples of Lavandula pedunculata (Mill.) Cav, and to compare aqueous and hydroethanolic extracts. Plant materials were obtained by growing some accessions (seed samples) of various wild [...] Read more.

The aim of this study was to characterize the phenolic composition and evaluate the bioactivity of several samples of Lavandula pedunculata (Mill.) Cav, and to compare aqueous and hydroethanolic extracts. Plant materials were obtained by growing some accessions (seed samples) of various wild populations from different regions of Portugal conserved at the Portuguese Genebank in Braga. Phenolic compounds were analised by HPLC-DAD-ESI/MSn, antioxidant potential through in vitro assays (DPPH radical scavenging activity, reducing power and inhibition of lipid peroxidation), cytotoxicity on tumor cells (MCF-7, NCI-H460, HeLa and HepG2) and non-tumor (PLP2) cells, anti-inflammatory activity in rat RAW 264.7 macrophages, by the ability to inhibit NO production and antimicrobial potential by the microdilution method with INT dye (iodonitrotetrazolium chloride). Thirteen compounds were identified, being salvianolic acid B, rosmarinic acid and luteolin-7-O-glucuronide, the main compounds present, with values ranging between 44.3–582, 50.9–550, and 24.36–101.5 mg/g extract, respectively. L. pedunculata aqueous extract revealed a higher antioxidant potential (EC₅₀ values between 14 to 530 μg/mL), which could be related to its higher concentration in phenolic compounds; however, the hydroethanolic extract showed a higher anti-inflammatory (lower EC₅₀ values than 124 μg/mL) potential and antiproliferative capacity (lower GI₅₀ values than 34 μg/mL). Thus, this study highlights the bioactive effects of this species and opens up possibilities of uses in food and pharmaceutical formulations. However, there are potential differences in such properties according to geographical origin of plant material, as in general, the samples from Alentejo presented higher results in all the bioactivities, compared with Trás-os-Montes samples. Full article

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13 pages, 1257 KiB

Open AccessArticle

Anticancer Profiling for Coumarins and Related O-Naphthoquinones from Mansonia gagei against Solid Tumor Cells In Vitro

by Mohammed A. Baghdadi, Fahad A. Al-Abbasi, Ali M. El-Halawany, Ali H. Aseeri and Ahmed M. Al-Abd

Molecules 2018, 23(5), 1020; https://doi.org/10.3390/molecules23051020 - 26 Apr 2018

Cited by 33 | Viewed by 5481

Abstract

Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds [...] Read more.

Napthoquinones and coumarins are naturally occurring compounds with potential anticancer activity. In the current study, two O-naphthoquinons (mansonone-G and mansonone-N) and six coumarins (mansorin-A, mansorin-B, mansorin-C, mansorins-I, mansorin-II, and mansorin-III) were isolated from the heartwood of Mansonia gagei family Sterculariaceae. Isolated compounds were examined for their potential anticancer activity against breast (MCF-7), cervix (HeLa), colorectal (HCT-116) and liver (HepG2) cancer cells using Sulfarhodamine-B (SRB) assay. Mansorin-II and mansorin-III showed relatively promising cytotoxic profile in all cell lines under investigation with inhibitory concentrations (IC₅₀s) in the range of 0.74 µM to 36 µM and 3.95 µM to 35.3 µM, respectively. In addition, mansorin-B, mansorin-C, mansorin-II and mansorin-III significantly increased cellular entrapment of the P-glycoprotein (P-gp) substrate, doxorubicin, in colorectal cancer cells expressing the P-gp pump. The inhibitory effect of the isolated compounds on P-gp pump was examined using human recombinant P-gp molecules attached to ATPase subunit. Mansorin-B and mansonone-G were found to inhibit the P-gp attached ATPase subunit. On the other hand, mansorin-C, mansorin-III and mansorin-II inhibited P-gp pump via dual action (P-gp related ATPase subunit inhibition and P-gp substrate binding site occupation). However, mansorin II was examined for its potential chemomodulatory effect to paclitaxel (PTX) against colorectal cancer cells (HCT-116 and CaCo-2). Mansorin-II significantly reduced the IC₅₀ of PTX in HCT-116 cells from 27.9 ± 10.2 nM to 5.1 ± 1.9 nM (synergism with combination index of 0.44). Additionally, Mansorin-II significantly reduced the IC₅₀ of PTX in CaCo-2 cells from 2.1 ± 0.8 µM to 0.13 ± 0.03 µM (synergism with combination index of 0.18). Furthermore, cell cycle analysis was studied after combination of mansorin-II with paclitaxel using DNA flow cytometry analysis. Synergism of mansorin-II and PTX was reflected in increasing apoptotic cell population in both HCT-116 and CaCo-2 cells compared to PTX treatment alone. Combination of mansorin-II with PTX in CaCo-2 cells significantly increased the cell population in G₂/M phase (from 2.9 ± 0.3% to 7.7 ± 0.8%) with reciprocal decrease in G₀/G1 cell fraction from 52.1 ± 1.1% to 45.5 ± 1.0%. Similarly in HCT-116 cells, mansorin-II with PTX significantly increased the cell population in G₂/M phase (from 33.4 ± 2.8% to 37.6 ± 1.3%) with reciprocal decrease in the S-phase cell population from 22.8 ± 1.7% to 20.2 ± 0.8%. In conclusion, mansorin-II synergizes the anticancer effect of paclitaxel in colorectal cancer cells, which might be partially attributed to enhancing its cellular entrapment via inhibiting P-gp efflux pump. Full article

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14 pages, 3230 KiB

Open AccessArticle

Formation of Sulforaphane and Iberin Products from Thai Cabbage Fermented by Myrosinase-Positive Bacteria

by Vijitra Luang-In, Sirirat Deeseenthum, Piyachat Udomwong, Worachot Saengha and Matteo Gregori

Molecules 2018, 23(4), 955; https://doi.org/10.3390/molecules23040955 - 19 Apr 2018

Cited by 23 | Viewed by 5816

Abstract

Myrosinase-positive bacteria from local fermented foods and beverages in Thailand with the capacity to metabolize glucosinolate and produce isothiocyanates (ITCs) were isolated and used as selected strains for Thai cabbage fermentation. Enterobacter xiangfangensis 4A-2A3.1 (EX) from fermented fish and Enterococcus casseliflavus SB2X2 (EC) [...] Read more.

Myrosinase-positive bacteria from local fermented foods and beverages in Thailand with the capacity to metabolize glucosinolate and produce isothiocyanates (ITCs) were isolated and used as selected strains for Thai cabbage fermentation. Enterobacter xiangfangensis 4A-2A3.1 (EX) from fermented fish and Enterococcus casseliflavus SB2X2 (EC) from fermented cabbage were the two highest ITC producers among seventeen strains identified by 16S rRNA technique. EC and EX were used to ferment Thai cabbage (Brassica oleracea L. var. capitata) containing glucoiberin, glucoraphanin and 4-hydroxyglucobrassicin at 430.5, 615.1 and 108.5 µmol/100 g DW, respectively for 3 days at 25 °C. Different amounts of iberin nitrile, iberin, sulforaphane and indole 3-acetonitrile were produced by spontaneous, EX- and EC-induced cabbage fermentations, and significantly higher ITCs were detected (p < 0.01) with increased antioxidant activities. Iberin and sulforaphane production in EX-induced treatment peaked on day 2 at 117.4 and 294.1 µmol/100 g DW, respectively, significantly higher than iberin at 51.7 µmol/100 g DW but not significantly higher than sulforaphane at 242.6 µmol/100 g DW in EC-induced treatment at day 2. Maximum health-promoting benefits from this functional food can be obtained from consumption of a liquid portion of the fermented cabbage with higher ITC level along with a solid portion. Full article

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12 pages, 8240 KiB

Open AccessArticle

Biflavonoids Isolated from Selaginella tamariscina and Their Anti-Inflammatory Activities via ERK 1/2 Signaling

by Sun-Yup Shim, Seul-gi Lee and Mina Lee

Molecules 2018, 23(4), 926; https://doi.org/10.3390/molecules23040926 - 17 Apr 2018

Cited by 45 | Viewed by 5438

Abstract

Selaginella tamariscina (S. tamariscina) (Beauv.) Spring (Selaginellaceae) has been used in oriental medicine for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus and metrorrhagia. In the present study, we isolated two strong anti-inflammatory compounds, the biflavonoids [...] Read more.

Selaginella tamariscina (S. tamariscina) (Beauv.) Spring (Selaginellaceae) has been used in oriental medicine for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus and metrorrhagia. In the present study, we isolated two strong anti-inflammatory compounds, the biflavonoids hinokiflavone (H) and 7′-O-methyl hinokiflavone (mH), from S. tamariscina and examined their anti-inflammatory activities in lipopolysaccharide (LPS)-mediated murine macrophages (RAW 264.7) and colon epithelial cells (HT-29). H and mH suppressed the production of the inflammatory mediators nitric oxide (NO), interleukin (IL)-6, IL-8, and tumor-necrosis factor (TNF)-α, which are most highly activated in inflammatory bowel disease (IBD). In addition, Western blot analysis revealed that H and mH suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2. These results suggest that H and mH are compounds having potent anti-inflammatory effects that could be used to treat such diseases as IBD. Full article

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14 pages, 12997 KiB

Open AccessArticle

Flavonoid 8-O-Glucuronides from the Aerial Parts of Malva verticillata and Their Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

by Jung-Hwan Ko, Youn Hee Nam, Sun-Woo Joo, Hyoung-Geun Kim, Yeong-Geun Lee, Tong Ho Kang and Nam-In Baek

Molecules 2018, 23(4), 833; https://doi.org/10.3390/molecules23040833 - 4 Apr 2018

Cited by 22 | Viewed by 6056

Abstract

Malva verticillata (Cluster mallow), a leafy vegetable that has been popular in East Asia for a long time, has also been used in herbal teas and medicines. The aqueous fraction of the aerial parts of Malva verticillata, exhibiting a very high quantity [...] Read more.

Malva verticillata (Cluster mallow), a leafy vegetable that has been popular in East Asia for a long time, has also been used in herbal teas and medicines. The aqueous fraction of the aerial parts of Malva verticillata, exhibiting a very high quantity of flavonoids compared to the EtOAc and n-BuOH fractions, exhibited significant recovery effects on pancreatic islets damaged by alloxan in zebrafish larvae. Thus, the bioactive components responsible for this anti-diabetic activity were investigated. A new flavonoid glucuronide (1) and five known flavonoids were isolated from the aqueous fraction. Based on several spectroscopic methods, compound 1 was identified to be nortangeretin-8-O-β-d-glucuronide, and was named malvaflavone A. The A-ring of compound 1 had a 5,6,7,8-tetrahydroxy moiety, which rarely occurs in plant systems. Also 8-O-glucuronide attached to the flavonoid moiety was rarely occurred in plant system. Compounds 1, 3, 4, and 6 significantly improved the pancreatic islet size in zebrafish at 0.1 μM, and compounds 1 and 6 were found to block β-cell K⁺ channels in experiments with diazoxide. In ABTS, ORAC, and SOD assays, compounds 1–5 exhibited high anti-oxidant activities compared with quercetin and BHA (positive controls), indicating that the 8-O-glucuronide attached to the flavonoid moiety is a key structure for the expression of anti-oxidant activity. This is the first report of the isolation of compounds 1–6 from M. verticillata as well evaluated for anti-diabetic and anti-oxidant ativities. Full article

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16 pages, 12488 KiB

Open AccessReview

Occurrence of Functional Molecules in the Flowers of Tea (Camellia sinensis) Plants: Evidence for a Second Resource

by Yiyong Chen, Ying Zhou, Lanting Zeng, Fang Dong, Youying Tu and Ziyin Yang

Molecules 2018, 23(4), 790; https://doi.org/10.3390/molecules23040790 - 29 Mar 2018

Cited by 60 | Viewed by 9587

Abstract

Tea (Camellia sinensis) is an important crop, and its leaves are used to make the most widely consumed beverage, aside from water. People have been using leaves from tea plants to make teas for a long time. However, less attention has [...] Read more.

Tea (Camellia sinensis) is an important crop, and its leaves are used to make the most widely consumed beverage, aside from water. People have been using leaves from tea plants to make teas for a long time. However, less attention has been paid to the flowers of tea plants, which is a waste of an abundant resource. In the past 15 years, researchers have attempted to discover, identify, and evaluate functional molecules from tea flowers, and have made insightful and useful discoveries. Here, we summarize the recent investigations into these functional molecules in tea flowers, including functional molecules similar to those in tea leaves, as well as the preponderant functional molecules in tea flowers. Tea flowers contain representative metabolites similar to those of tea leaves, such as catechins, flavonols, caffeine, and amino acids. The preponderant functional molecules in tea flowers include saponins, polysaccharides, aromatic compounds, spermidine derivatives, and functional proteins. We also review the safety and biological functions of tea flowers. Tea flower extracts are proposed to be of no toxicological concern based on evidence from the evaluation of mutagenicity, and acute and subchronic toxicity in rats. The presence of many functional metabolites in tea flowers indicates that tea flowers possess diverse biological functions, which are mostly related to catechins, polysaccharides, and saponins. Finally, we discuss the potential for, and challenges facing, future applications of tea flowers as a second resource from tea plants. Full article

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17 pages, 20782 KiB

Open AccessArticle

Intraconversion of Polar Ginsenosides, Their Transformation into Less-Polar Ginsenosides, and Ginsenoside Acetylation in Ginseng Flowers upon Baking and Steaming

by Xiang Li, Fan Yao, Hang Fan, Ke Li, Liwei Sun and Yujun Liu

Molecules 2018, 23(4), 759; https://doi.org/10.3390/molecules23040759 - 26 Mar 2018

Cited by 21 | Viewed by 5596

Abstract

Heating is a traditional method used in ginseng root processing, however, there aren’t reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation [...] Read more.

Heating is a traditional method used in ginseng root processing, however, there aren’t reports on differences resulting from baking and steaming. Moreover, ginseng flowers, with 5.06 times more total saponins than ginseng root, are not fully taken advantage of for their ginsenosides. Transformation mechanisms of ginsenosides in ginseng flowers upon baking and steaming were thus explored. HPLC using authentic standards of 20 ginsenosides and UPLC-QTOF-MS/MS were used to quantify and identify ginsenosides, respectively, in ginseng flowers baked or steamed at different temperatures and durations. Results show that baking and steaming caused a 3.2-fold increase in ginsenoside species existed in unheated ginseng flowers (20/64 ginsenosides) and transformation of a certain amount of polar ginsenosides into numerous less polar ginsenosides. Among the 20 ginsenosides with standards, polar ginsenosides were abundant in ginseng flowers baked or steamed at lower temperatures, whereas less polar ginsenosides occurred and were enriched at higher temperatures. Furthermore, the two types of heating treatments could generate mostly similar ginsenosides, but steaming was much efficient than baking in transforming polar- into less polar ginsenosides, with steaming at 120 °C being comparably equivalent to baking at 150 °C. Moreover, both the two heating methods triggered ginsenoside acetylation and thus caused formation of 16 acetylginsenosides. Finally, a new transformation mechanism concerning acetyl-ginsenosides formation was proposed. Full article

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9 pages, 1056 KiB

Open AccessArticle

Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors

by Daniela Hulcová, Kateřina Breiterová, Tomáš Siatka, Kamila Klímová, Lara Davani, Marcela Šafratová, Anna Hošťálková, Angela De Simone, Vincenza Andrisano and Lucie Cahlíková

Molecules 2018, 23(4), 719; https://doi.org/10.3390/molecules23040719 - 21 Mar 2018

Cited by 26 | Viewed by 5839

Abstract

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating [...] Read more.

Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3β is one of the most attractive targets for medicinal chemists in the discovery, design, and synthesis of new selective potent inhibitors. In the current study, twenty-eight Amaryllidaceae alkaloids of various structural types were studied for their potency to inhibit GSK-3β. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC₅₀ = 30.00 ± 0.71 µM), masonine (IC₅₀ = 27.81 ± 0.01 μM)}, and lycorine-types {caranine (IC₅₀ = 30.75 ± 0.04 μM)}. Full article

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8 pages, 1228 KiB

Open AccessArticle

Hyperjaponol H, A New Bioactive Filicinic Acid-Based Meroterpenoid from Hypericum japonicum Thunb. ex Murray

by Rongrong Wu, Zijun Le, Zhenzhen Wang, Shuying Tian, Yongbo Xue, Yong Chen, Linzhen Hu and Yonghui Zhang

Molecules 2018, 23(3), 683; https://doi.org/10.3390/molecules23030683 - 18 Mar 2018

Cited by 14 | Viewed by 5210

Abstract

Hyperjaponol H (1), a new filicinic acid-based meroterpenoid, with a 6/6/10 ring system trans-fused by hetero-Diels–Alder cycloaddition between a germacrane sesquiterpenoid and a filicinic acid moiety, was isolated from aerial parts of Hypericum japonicum. The elucidation of its structure [...] Read more.

Hyperjaponol H (1), a new filicinic acid-based meroterpenoid, with a 6/6/10 ring system trans-fused by hetero-Diels–Alder cycloaddition between a germacrane sesquiterpenoid and a filicinic acid moiety, was isolated from aerial parts of Hypericum japonicum. The elucidation of its structure and absolute configuration were accomplished by the analyses of extensive spectroscopic data and the comparison of Cotton effects of electron circular dichroism (ECD) with previously reported ones. The bioactivity assay showed that hyperjaponol H exhibited a moderate inhibitory efficacy on lytic Epstein-Barr virus (EBV) DNA replication in B95-8 cells. Full article

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31 pages, 5373 KiB

Open AccessReview

Structural Diversity and Biological Activities of Novel Secondary Metabolites from Endophytes

by Han Gao, Gang Li and Hong-Xiang Lou

Molecules 2018, 23(3), 646; https://doi.org/10.3390/molecules23030646 - 13 Mar 2018

Cited by 93 | Viewed by 10222

Abstract

Exploration of structurally novel natural products greatly facilitates the discovery of biologically active pharmacophores that are biologically validated starting points for the development of new drugs. Endophytes that colonize the internal tissues of plant species, have been proven to produce a large number [...] Read more.

Exploration of structurally novel natural products greatly facilitates the discovery of biologically active pharmacophores that are biologically validated starting points for the development of new drugs. Endophytes that colonize the internal tissues of plant species, have been proven to produce a large number of structurally diverse secondary metabolites. These molecules exhibit remarkable biological activities, including antimicrobial, anticancer, anti-inflammatory and antiviral properties, to name but a few. This review surveys the structurally diverse natural products with new carbon skeletons, unusual ring systems, or rare structural moieties that have been isolated from endophytes between 1996 and 2016. It covers their structures and bioactivities. Biosynthesis and/or total syntheses of some important compounds are also highlighted. Some novel secondary metabolites with marked biological activities might deserve more attention from chemists and biologists in further studies. Full article

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7 pages, 1315 KiB

Open AccessCommunication

Prenylated Polyphenols from Broussonetia kazinoki as Inhibitors of Nitric Oxide Production

by Da Yeon Lee, Hwa Jin Lee and Jae-Ha Ryu

Molecules 2018, 23(3), 639; https://doi.org/10.3390/molecules23030639 - 12 Mar 2018

Cited by 7 | Viewed by 4213

Abstract

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols (1–7) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, [...] Read more.

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols (1–7) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols (2–4 and 6) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC₅₀ values of less than 6 µM. The compounds 2–4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor κB (NF-κB) activity by inhibiting the degradation of inhibitory-κB-α (I-κB-α) and the translocation of NF-κB into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases. Full article

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12 pages, 2684 KiB

Open AccessArticle

Multi-Target Anti-Alzheimer Activities of Four Prenylated Compounds from Psoralea Fructus

by Qing-Xia Xu, Ying Hu, Gui-Yang Li, Wei Xu, Ying-Tao Zhang and Xiu-Wei Yang

Molecules 2018, 23(3), 614; https://doi.org/10.3390/molecules23030614 - 8 Mar 2018

Cited by 39 | Viewed by 5759

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF [...] Read more.

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloid β-peptide 42, β-secretase, glycogen synthase kinase 3β, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment. Full article

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12 pages, 557 KiB

Open AccessArticle

New Terpenoids from Chamaecyparis formosensis (Cupressaceae) Leaves with Modulatory Activity on Matrix Metalloproteases 2 and 9

by Meng-Lun Chang, Hui-Ching Mei, I-Chih Kuo, George Hsiao, Yueh-Hsiung Kuo and Ching-Kuo Lee

Molecules 2018, 23(3), 604; https://doi.org/10.3390/molecules23030604 - 7 Mar 2018

Cited by 1 | Viewed by 4269

Abstract

Chamaecyparis formosensis is Taiwan’s most representative tree, and has high economic value. To date, only a few active chemical constituents have been reported for C. formosensis. In this study, 37 secondary metabolites, including three new compounds (1–3), were [...] Read more.

Chamaecyparis formosensis is Taiwan’s most representative tree, and has high economic value. To date, only a few active chemical constituents have been reported for C. formosensis. In this study, 37 secondary metabolites, including three new compounds (1–3), were extracted from the leaves of C. formosensis. The compounds isolated from the ethyl acetate layer were used at different concentrations to treat HT-1080 human fibrosarcoma cells and to evaluate their effects on matrix metalloprotease 2 (MMP-2) and 9 (MMP-9) expression. Based on extensive analysis of data from high-resolution mass spectrometry (HR-MS) as well as nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV) spectroscopy, the new compounds were identified as 11,12-dihydroxyisodaucenoic acid (1), 12-hydroxyisodaucenoic acid (2), and 1-oxo-2α,3β-dihydroxytotarol (3). Known compounds 4–37 were identified by comparing their spectroscopic data with data reported in the literature. Biological activity tests by gelatin zymographic analysis revealed that seven compounds, including new compound 2, have no cytotoxic effect on HT-1080 cells and were found to increase MMP-2 or MMP-9 expression by 1.25- to 1.59-fold at lower concentrations of 10–50 µM. These naturally derived regulatory compounds could potentially serve as a novel pharmaceutical basis for medical purposes. Full article

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11 pages, 7297 KiB

Open AccessArticle

Wedelolactone Enhances Osteoblastogenesis through ERK- and JNK-mediated BMP2 Expression and Smad/1/5/8 Phosphorylation

by Di Zhu, Xue Deng, Xiao-Fei Han, Xiao-Xin Sun, Tao-Wen Pan, Lu-Ping Zheng and Yan-Qiu Liu

Molecules 2018, 23(3), 561; https://doi.org/10.3390/molecules23030561 - 2 Mar 2018

Cited by 28 | Viewed by 6510

Abstract

Our previous study showed that wedelolactone, a compound isolated from Ecliptae herba, has the potential to enhance osteoblastogenesis. However, the molecular mechanisms by which wedelolactone promoted osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs) remain largely unknown. In this study, treatment with [...] Read more.

Our previous study showed that wedelolactone, a compound isolated from Ecliptae herba, has the potential to enhance osteoblastogenesis. However, the molecular mechanisms by which wedelolactone promoted osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs) remain largely unknown. In this study, treatment with wedelolactone (2 μg/mL) for 3, 6, and 9 days resulted in an increase in phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal protein kinase (JNK), and p38. Phosphorylation of mitogen-activated protein kinases (MAPKs), ERK and JNK started to increase on day 3 of treatment, and p38 phosphorylation was increased by day 6 of treatment. Expression of bone morphogenetic protein (BMP2) mRNA and phosphorylation of Smad1/5/8 was enhanced after treatment of cells with wedelolactone for 6 and 9 days. The addition of the JNK inhibitor SP600125, ERK inhibitor PD98059, and p38 inhibitor SB203580 suppressed wedelolactone-induced alkaline-phosphatase activity, bone mineralization, and osteoblastogenesis-related marker genes including Runx2, Bglap, and Sp7. Increased expression of BMP2 mRNA and Smad1/5/8 phosphorylation was blocked by SP600125 and PD98059, but not by SB203580. These results suggested that wedelolactone enhanced osteoblastogenesis through induction of JNK- and ERK-mediated BMP2 expression and Smad1/5/8 phosphorylation. Full article

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13 pages, 1232 KiB

Open AccessArticle

Persicaline, A New Antioxidant Sulphur-Containing Imidazoline Alkaloid from Salvadora persica Roots

by Mohamed Farag, Wael M. Abdel-Mageed, Omer Basudan and Ali El-Gamal

Molecules 2018, 23(2), 483; https://doi.org/10.3390/molecules23020483 - 23 Feb 2018

Cited by 26 | Viewed by 5900

Abstract

Salvadora persica L. is a popular chewing stick commonly known as “miswak”. During our ongoing research activities on the chemical constituents of Salvadora persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3-Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione, persicaline, (1) along with five known compounds ( [...] Read more.

Salvadora persica L. is a popular chewing stick commonly known as “miswak”. During our ongoing research activities on the chemical constituents of Salvadora persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3-Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione, persicaline, (1) along with five known compounds (2–6) are identified. Compounds (2, 3) were reported for the first time from the family Salvadoraeceae. The structure of the new compound was established by extensive spectroscopic data and HR-MS. The antioxidant activities of the fractions and isolates were evaluated using different in vitro methods, such as DPPH, superoxide anion and nitric oxide radicals scavenging assays. Compound (1) showed a promising antioxidant activity with IC₅₀ 0.1, 0.08, and 0.09 µM in the three assays, respectively, comparable to ascorbic acid. Full article

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9 pages, 589 KiB

Open AccessArticle

Bioactive Phenolic and Isocoumarin Glycosides from the Stems of Homalium paniculiflorum

by Shou-Yuan Wu, Yan-Hui Fu, Qi Zhou, Meng Bai, Guang-Ying Chen, Si-Yu Zhao, Chang-Ri Han and Xiao-Ping Song

Molecules 2018, 23(2), 472; https://doi.org/10.3390/molecules23020472 - 22 Feb 2018

Cited by 7 | Viewed by 4585

Abstract

Two new phenolic glycosides (1 and 2) and two new isocoumarin glycosides (3 and 4), along with 14 known compounds (5–18), were isolated from the stems of Homalium paniculiflorum. Their structures were established on [...] Read more.

Two new phenolic glycosides (1 and 2) and two new isocoumarin glycosides (3 and 4), along with 14 known compounds (5–18), were isolated from the stems of Homalium paniculiflorum. Their structures were established on the basis of extensive spectroscopic analyses and chemical methods. All new compounds were evaluated for their anti-inflammatory activities via examining the inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in mouse macrophage RAW 264.7 cells in vitro. Compounds 1 and 4 exhibited inhibitory activities with IC₅₀ values of 30.23 ± 1.23 μM and 19.36 ± 0.19 μM, respectively. Full article

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17 pages, 2377 KiB

Open AccessArticle

Comparative Analysis of Chemical Composition, Antioxidant Activity and Quantitative Characterization of Some Phenolic Compounds in Selected Herbs and Spices in Different Solvent Extraction Systems

by Shabnam Sepahpour, Jinap Selamat, Mohd Yazid Abdul Manap, Alfi Khatib and Ahmad Faizal Abdull Razis

Molecules 2018, 23(2), 402; https://doi.org/10.3390/molecules23020402 - 13 Feb 2018

Cited by 146 | Viewed by 13664

Abstract

This study evaluated the efficacy of various organic solvents (80% acetone, 80% ethanol, 80% methanol) and distilled water for extracting antioxidant phenolic compounds from turmeric, curry leaf, torch ginger and lemon grass extracts. They were analyzed regarding the total phenol and flavonoid contents, [...] Read more.

This study evaluated the efficacy of various organic solvents (80% acetone, 80% ethanol, 80% methanol) and distilled water for extracting antioxidant phenolic compounds from turmeric, curry leaf, torch ginger and lemon grass extracts. They were analyzed regarding the total phenol and flavonoid contents, antioxidant activity and concentration of some phenolic compounds. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and the ferric reducing antioxidant power (FRAP) assay. Quantification of phenolic compounds was carried out using high-performance liquid chromatography (HPLC). All the extracts possessed antioxidant activity, however, the different solvents showed different efficiencies in the extraction of phenolic compounds. Turmeric showed the highest DPPH values (67.83–13.78%) and FRAP (84.9–2.3 mg quercetin/g freeze-dried crude extract), followed by curry leaf, torch ginger and lemon grass. While 80% acetone was shown to be the most efficient solvent for the extraction of total phenolic compounds from turmeric, torch ginger and lemon grass (221.68, 98.10 and 28.19 mg GA/g freeze dried crude extract, respectively), for the recovery of phenolic compounds from curry leaf (92.23 mg GA/g freeze-dried crude extract), 80% ethanol was the most appropriate solvent. Results of HPLC revealed that the amount of phenolic compounds varied depending on the types of solvents used. Full article

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16 pages, 908 KiB

Open AccessArticle

Bioactive Compounds in Cornelian Cherry Vinegars

by Joanna Kawa-Rygielska, Kinga Adamenko, Alicja Z. Kucharska and Narcyz Piórecki

Molecules 2018, 23(2), 379; https://doi.org/10.3390/molecules23020379 - 10 Feb 2018

Cited by 40 | Viewed by 5919

Abstract

We analyzed the effect of Cornelian cherry varieties differing in fruit color (‘Yantaryi’—yellow fruits, ‘Koralovyi’—coral fruits, ‘Podolski’—red fruits) and the production method on the physicochemical and antioxidative properties of Cornelian cherry vinegars, and on their content of iridoids and polyphenols. Acetic fermentation was [...] Read more.

We analyzed the effect of Cornelian cherry varieties differing in fruit color (‘Yantaryi’—yellow fruits, ‘Koralovyi’—coral fruits, ‘Podolski’—red fruits) and the production method on the physicochemical and antioxidative properties of Cornelian cherry vinegars, and on their content of iridoids and polyphenols. Acetic fermentation was conducted by two methods: I) single-stage (spontaneous) acetic fermentation, without inoculation with microorganisms, and II) two-stage fermentation in which the first stage involved the use of Saccharomyces bayanus—Safspirit fruit yeast for alcoholic fermentation, and the second one included spontaneous acetic fermentation. Acetic acid, glycerol, individual iridoids, phenolic acids, flavonols, and anthocyanins were quantified by a high-performance liquid chromatography (HPLC) method. The antioxidative activity was determined based on the following tests: 2,2-Diphenyl-2-picryl-hydrazyl (DPPH^•), 2,2′-Azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS^•+), and ferric reducing antioxidant power (FRAP), while the total polyphenols content was determined using the Folin-Ciocialteu (F-C) reagent test. Both the Cornelian cherry variety and vinegar production method affected the antioxidative properties as well as concentrations of iridoids and polyphenols in the finished product. The concentration of total polyphenols (F-C) in vinegars ranged from 326.60 to 757.27 mg gallic acids equivalents (GAE)/100 mL vinegar, whereas the antioxidative activity assayed with the DPPH^• and FRAP methods was the highest in the vinegars produced from the coral and red varieties of Cornelian cherry with the two-stage method. Loganic acid predominated among the identified iridoids, reaching a concentration of 185.07 mg loganic acid (LA)/100 mL in the vinegar produced in the two-stage fermentation from the coral-fruit variety. Caffeoylquinic acid derivatives were the main representatives among the identified phenolic compounds. The results of this study demonstrate Cornelian cherry vinegars to be rich sources of biologically-active iridoids and phenolic compounds with antioxidative properties. Full article

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10 pages, 2614 KiB

Open AccessArticle

Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets

by Michal Bijak, Rafal Szelenberger, Angela Dziedzic and Joanna Saluk-Bijak

Molecules 2018, 23(2), 374; https://doi.org/10.3390/molecules23020374 - 10 Feb 2018

Cited by 15 | Viewed by 4872

Abstract

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly [...] Read more.

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets’ aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets’ ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation. Full article

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15 pages, 453 KiB

Open AccessArticle

Weed Suppressing Potential and Isolation of Potent Plant Growth Inhibitors from Castanea crenata Sieb. et Zucc

by Phung Thi Tuyen, Tran Dang Xuan, Truong Thi Tu Anh, Truong Mai Van, Ateeque Ahmad, Abdelnaser Abdelghany Elzaawely and Tran Dang Khanh

Molecules 2018, 23(2), 345; https://doi.org/10.3390/molecules23020345 - 7 Feb 2018

Cited by 27 | Viewed by 5557

Abstract

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli [...] Read more.

This study isolated, determined, and quantified plant growth inhibitors in Japanese chestnut (Castanea crenata Sieb. et Zucc), a deciduous species native to Japan and Korea. In laboratory assays, C. crenata leaves showed strong inhibition on germination and seedling growth of Echinochloa crus-galli (barnyardgrass), Lactuca sativa (lettuce), and Raphanus sativus (radish). Laboratory and greenhouse trials showed that leaves of C. crenata appeared as a promising material to manage weeds, especially the dicot weeds. By GC-MS and HPLC analyses, gallic, protocatechuic, p-hydroxybenzoic, caffeic, ferulic, ellagic, and cinnamic acids were identified and quantified, of which ellagic acid was present in the highest quantity (2.36 mg/g dried leaves). By column chromatography and spectral data (¹H- and ¹³C-NMR, IR, and LC-MS) analysis, a compound identified as 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid (1) was purified from the methanolic leaf extract of C. crenata (0.93 mg/g dried leaves). This constituent showed potent inhibition on growth of E. crus-galli, a problematic weed in agricultural practice. The inhibition of the compound 1 (IC₅₀ = 2.62 and 0.41 mM) was >5 fold greater than that of p-hydroxybenzoic acid (IC₅₀ = 15.33 and 2.11 mM) on shoot and root growth of E. crus-galli, respectively. Results suggest that the isolated the compound 1 has potential to develop natural herbicides to manage E. crus-galli. This study is the first to isolate and identify 2α,3β,7β,23-tetrahydroxyurs-12-ene-28-oic acid in a plant and report its plant growth inhibitory potential. Full article

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14 pages, 2029 KiB

Open AccessArticle

Nutritional Value, Chemical Characterization and Bulb Morphology of Greek Garlic Landraces

by Spyridon A. Petropoulos, Ângela Fernandes, Georgia Ntatsi, Konstantinos Petrotos, Lillian Barros and Isabel C. F. R. Ferreira

Molecules 2018, 23(2), 319; https://doi.org/10.3390/molecules23020319 - 2 Feb 2018

Cited by 49 | Viewed by 7592

Abstract

Garlic (Allium sativum L.) is an important vegetable crop throughout the world. In Greece there are many areas which have specialized in garlic cultivation through the last decades, considered the main production areas. However, despite the significance of garlic as a food [...] Read more.

Garlic (Allium sativum L.) is an important vegetable crop throughout the world. In Greece there are many areas which have specialized in garlic cultivation through the last decades, considered the main production areas. However, despite the significance of garlic as a food product and the high annual income of this crop, there is a decreasing trend in total cultivated area in Greece, and the local landraces are gradually neglected in favor of new imported genotypes. In the present study, garlic genotypes (local landraces/varieties, imported genotypes, commercial cultivars) from the main production regions of Greece were assessed for their chemical composition and quality (total soluble solids, dry matter content, nutritional value, mineral composition, organic acids, fatty acids content and free sugars content), and bulb morphology. The results of the present study showed significant diversity in quality features and bulb morphology, not only between the genotypes from different growing regions, but also between those of the same region. This result is interesting since it could be implemented for further improvement and valorization of this important vegetable crop through extensive breeding programs within the framework of sustainability and genetic, material conservation. Full article

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13 pages, 2280 KiB

Open AccessArticle

Estrogenic Effects of the Extracts from the Chinese Yam (Dioscorea opposite Thunb.) and Its Effective Compounds in Vitro and in Vivo

by Mengnan Zeng, Li Zhang, Miao Li, Beibei Zhang, Ning Zhou, Yingying Ke, Weisheng Feng and Xiaoke Zheng

Molecules 2018, 23(2), 11; https://doi.org/10.3390/molecules23020011 - 23 Jan 2018

Cited by 46 | Viewed by 6356

Abstract

Background: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. Methods: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast [...] Read more.

Background: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. Methods: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast cancer cell lines (MCF-7 cell); the estrogenic activity was comprehensively evaluated by a serum pharmacology experiment. The levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were also measured. Western blot analysis and antagonist assays with faslodex (ICI182,780), methylpiperidino-pyrazole (MPP), Delta (9) –tetrahydrocannabinol (THC), and G-15 were used to explore the mechanism of the effects of the yam. To find the effective compounds of the yam which play a role in its estrogen-like effects, we used the same methods to study the effects of adenosine and arbutin. Results: The Chinese yam and two main compounds, adenosine and arbutin, have estrogen-like effects. The mechanism of the yam which plays a role in its estrogen-like effects was mainly mediated by the estrogen receptors ERα, ERβ, and GPR30; that of adenosine was mainly mediated by estrogen receptors ERα and ERβ, and that of arbutin was mainly mediated by estrogen receptors ERβ and GPR30. Conclusions: The Chinese yam has estrogen-like effects; adenosine and arbutin are two of the effective compounds in the yam which play a role in its estrogen-like effects. Full article

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11 pages, 2783 KiB

Open AccessArticle

Bioactivity-Guided Screening of Wound-Healing Active Constituents from American Cockroach (Periplaneta americana)

by Juan-Juan Zhu, Shun Yao, Xin Guo, Bi-Song Yue, Xiu-Ying Ma and Jing Li

Molecules 2018, 23(1), 101; https://doi.org/10.3390/molecules23010101 - 20 Jan 2018

Cited by 44 | Viewed by 6925

Abstract

Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ulcers. We compared the wound-healing activities of three extracts [...] Read more.

Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ulcers. We compared the wound-healing activities of three extracts of PA using cutaneous wound-healing in mice as the bioactivity model. These three extracts were EE, total polysaccharide and total protein. We also tracked bioactive fractions in the EE by organic reagent extraction, column chromatography and HPLC. Seven compounds were successfully identified from the water elution fraction of the EE of PA using UPLC-MS. Among these compounds, four compounds (P2, P3, P4, P5(1)) were first reported in PA. Some of these compounds have been previously reported to have various pharmacological activities that could contribute to the high wound-healing activity of PA. Full article

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9 pages, 918 KiB

Open AccessCommunication

Modulation of Inducible Nitric Oxide Synthase Expression in LPS-Stimulated BV-2 Microglia by Prenylated Chalcones from Cullen corylifolium (L.) Medik. through Inhibition of I-κBα Degradation

by Do Hee Kim, Hua Li, Yeong Eun Han, Ji Hye Jeong, Hwa Jin Lee and Jae-Ha Ryu

Molecules 2018, 23(1), 109; https://doi.org/10.3390/molecules23010109 - 4 Jan 2018

Cited by 41 | Viewed by 5891

Abstract

The overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by microglia may cause neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were [...] Read more.

The overproduction of nitric oxide (NO) and prostaglandin E₂ (PGE₂) by microglia may cause neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone (1), bavachromene (2), and kanzonol B (3). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE₂ production in lipopolysaccharide (LPS)-activated microglia. Western blotting and RT-PCR analysis demonstrated that these prenylchalcones reduced the expression of protein and mRNA of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-activated microglia. Furthermore, three prenylated chalcones blocked the inhibitory-κBα (I-κBα) degradation and down-regulated nuclear factor κB (NF-κB) level of nucleus in LPS-stimulated BV-2 microglia. Therefore, these prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating iNOS and COX-2 expressions in activated microglial cells. Full article

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18140 KiB

Open AccessArticle

Antrodia cinnamomea Oligosaccharides Suppress Lipopolysaccharide-Induced Inflammation through Promoting O-GlcNAcylation and Repressing p38/Akt Phosphorylation

by Junping Zheng, Siming Jiao, Qiongyu Li, Peiyuan Jia, Heng Yin, Xiaoming Zhao, Yuguang Du and Hongtao Liu

Molecules 2018, 23(1), 51; https://doi.org/10.3390/molecules23010051 - 26 Dec 2017

Cited by 23 | Viewed by 5536

Abstract

Antrodia cinnamomea (AC), an edible fungus growing in Taiwan, has various health benefits. This study was designed to examine the potential inhibitory effects of AC oligosaccharides on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. By trifluoroacetic acid degradation, two oligosaccharide products [...] Read more.

Antrodia cinnamomea (AC), an edible fungus growing in Taiwan, has various health benefits. This study was designed to examine the potential inhibitory effects of AC oligosaccharides on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. By trifluoroacetic acid degradation, two oligosaccharide products were prepared from AC polysaccharides at 90 °C (ACHO) or 25 °C (ACCO), which showed different oligosaccharide identities. Compared to ACCO, ACHO displayed better inhibitory effects on LPS-induced mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, IL-1β, TNF-α and MCP-1 in macrophage cells. Further, ACHO significantly suppressed the inflammation in lung tissues of LPS-injected C57BL/6 mice. The potential anti-inflammatory molecular mechanism may be associated with the promotion of protein O-GlcNAcylation, which further skewed toward the marked suppression of p38 and Akt phosphorylation. Our results suggest that the suppressive effect of AC oligosaccharides on inflammation may be an effective approach for the prevention of inflammation-related diseases. Full article

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420 KiB

Open AccessArticle

Antimicrobial Furoquinoline Alkaloids from Vepris lecomteana (Pierre) Cheek & T. Heller (Rutaceae)

by Ariane Dolly Kenmogne Kouam, Achille Nouga Bissoue, Alain Tadjong Tcho, Emmanuel Ngeufa Happi, Alain François Kamdem Waffo, Norbert Sewald and Jean Duplex Wansi

Molecules 2018, 23(1), 13; https://doi.org/10.3390/molecules23010013 - 21 Dec 2017

Cited by 16 | Viewed by 5665

Abstract

Three new prenylated furoquinoline alkaloids named lecomtequinoline A (1), B (2), and C (3), together with the known compounds anhydroevoxine (4), evoxine (5), dictamnine (6), N-methylflindersine (7), evoxanthine [...] Read more.

Three new prenylated furoquinoline alkaloids named lecomtequinoline A (1), B (2), and C (3), together with the known compounds anhydroevoxine (4), evoxine (5), dictamnine (6), N-methylflindersine (7), evoxanthine (8), hesperidin, lupeol, β-sitosterol, stigmasterol, β-sitosterol-3-O-β-d-glucopyranoside, stearic acid, and myristyl alcohol, were isolated by bioassay-guided fractionation of the methanolic extracts of leaves and stem of Vepris lecomteana. The structures of compounds were determined by spectroscopic methods (NMR, MS, UV, and IR) and by comparison with previously reported data. Crude extracts of leaves and stem displayed high antimicrobial activity, with Minimum Inhibitory Concentration (MIC) (values of 10.1–16.5 and 10.2–20.5 µg/mL, respectively, against Escherichia coli, Bacillus subtilis, Pseudomonas agarici, Micrococcus luteus, and Staphylococcus warneri, while compounds 1–6 showed values ranging from 11.1 to 18.7 µg/mL or were inactive, suggesting synergistic effect. The extracts may find application in crude drug preparations in Western Africa where Vepris lecomteana is endemic, subject to negative toxicity results in vivo. Full article

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3388 KiB

Open AccessArticle

Bioactive Compounds from the Stems of Clausena lansium

by Jie Liu, Chuang-Jun Li, Yi-Qian Du, Li Li, Hua Sun, Nai-Hong Chen and Dong-Ming Zhang

Molecules 2017, 22(12), 2226; https://doi.org/10.3390/molecules22122226 - 14 Dec 2017

Cited by 12 | Viewed by 5269

Abstract

In view of the significant neuroprotective effect of Clausena lansium, we continued to separate the n-butanol and the water extracts from the stems of C. lansium in order to find the leading compounds with significant activity. Two new phenolic glycosides, Clausenolside [...] Read more.

In view of the significant neuroprotective effect of Clausena lansium, we continued to separate the n-butanol and the water extracts from the stems of C. lansium in order to find the leading compounds with significant activity. Two new phenolic glycosides, Clausenolside A–B (1–2), one new pair of phenolic enantiomers (3a, 3b), and two new monoterpenoids, clausenapene A–B (4–5), together with twelve known analogues (6–17) were isolated from the stems of C. lansium. Compounds 1–17 were obtained from C. lansium for the first time. Compounds 3a, 3b, 4, 16, and 17 showed strong or moderate potential neuroprotective effects on inhibited PC12 cell injury induced by okadaic acid, and compound 9 exhibited strong potential hepatoprotective activities. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, NMR experiments, and electronic circular dichroism (ECD) spectra. Full article

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Open AccessArticle

Sequential Combination of Microwave- and Ultrasound-Assisted Extraction of Total Flavonoids from Osmanthus fragrans Lour. Flowers

by Jianfeng Yu, Qi Lou, Xiangyang Zheng, Zhengwei Cui and Jian Fu

Molecules 2017, 22(12), 2216; https://doi.org/10.3390/molecules22122216 - 13 Dec 2017

Cited by 38 | Viewed by 7464

Abstract

Microwave-assisted and ultrasound-assisted extraction assays were used to isolate total flavonoids (TF) from Osmanthus fragrans flowers. The effects of the solid-liquid ratio, ethanol concentration, microwave power, microwave extraction time, ultrasonic power and ultrasonic extraction time on the yield of TF were studied. A [...] Read more.

Microwave-assisted and ultrasound-assisted extraction assays were used to isolate total flavonoids (TF) from Osmanthus fragrans flowers. The effects of the solid-liquid ratio, ethanol concentration, microwave power, microwave extraction time, ultrasonic power and ultrasonic extraction time on the yield of TF were studied. A sequential combination of microwave- and ultrasound-assisted extraction (SC-MUAE) methods was developed, which was subsequently optimized by Box-Behnken design-response surface methodology (BBD-RSM). The interaction effects of the ethanol concentration (40–60%), microwave extraction time (5–7 min), ultrasonic extraction time (8–12 min) and ultrasonic power (210–430 W) on the yield of TF were investigated. The optimum operating parameters for the extraction of TF were determined to be as follows: ethanol concentration (48.15%), microwave extraction time (6.43 min), ultrasonic extraction time (10.09 min) and ultrasonic power (370.9 W). Under these conditions, the extraction yield of TF was 7.86 mg/g. Full article

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Open AccessArticle

Preparation, Characterization, and Biological Activities of Topical Anti-Aging Ingredients in a Citrus junos Callus Extract

by Deepak Adhikari, Vijay Kumar Panthi, Rudra Pangeni, Hyun Jung Kim and Jin Woo Park

Molecules 2017, 22(12), 2198; https://doi.org/10.3390/molecules22122198 - 11 Dec 2017

Cited by 19 | Viewed by 6801

Abstract

In this study, we prepared and characterized a callus extract from Citrus junos and assessed its utility as a source of topical anti-aging ingredients. Callus extract was produced by aqueous extraction from Citrus junos grown on Murashige and Skoog medium with picloram as [...] Read more.

In this study, we prepared and characterized a callus extract from Citrus junos and assessed its utility as a source of topical anti-aging ingredients. Callus extract was produced by aqueous extraction from Citrus junos grown on Murashige and Skoog medium with picloram as a growth regulator. After measuring the total phenolic and flavonoid contents, the major phenolic compound in calli was identified as p-hydroxycinnamoylmalic acid (1) by spectroscopic analysis. The total phenol content in the extract was determined to be 24.50 ± 0.43 mg/g of gallic acid equivalents; however, the total flavonoid content of the extract was not determined. The biological activities of the callus extract, in terms of skin anti-aging, were assessed by measuring the anti-tyrosinase activity in, and melanogenesis by, melanoma cells; and proliferation of, and procollagen synthesis by, human fibroblasts. The callus extract was incorporated into nanoliposomes (NLs) to improve its percutaneous absorption. Addition of the callus extract resulted in a 1.85-fold decrease in the melanin content of melanocytes compared with that with arbutin. The extract (500 μg/mL) significantly promoted the proliferation of, and procollagen synthesis by, fibroblasts (by 154% and 176%, respectively). In addition, the flux through the human epidermis of Citrus junos callus extract incorporated into NLs was 17.67-fold higher than that of the callus extract alone. These findings suggest that Citrus junos callus extract-loaded NLs have promise as an anti-aging cosmetic, as well as having a skin-lightening effect. Full article

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Open AccessArticle

Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark

by Nellie Francezon, Naamwin-So-Bâwfu Romaric Meda and Tatjana Stevanovic

Molecules 2017, 22(12), 2118; https://doi.org/10.3390/molecules22122118 - 1 Dec 2017

Cited by 18 | Viewed by 5885

Abstract

Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several [...] Read more.

Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several extraction parameters were tested and extracts obtained analyzed both in terms of relative amounts of different phytochemical families and of individual molecules concentrations. As a result, low temperature (80 °C) and low ratio of bark/water (50 mg/mL) were determined to be the best parameters for an efficient polyphenol extraction and that especially for low molecular mass polyphenols. These were identified as stilbene monomers and derivatives, mainly stilbene glucoside isorhapontin (up to 12.0% of the dry extract), astringin (up to 4.6%), resveratrol (up to 0.3%), isorhapontigenin (up to 3.7%) and resveratrol glucoside piceid (up to 3.1%) which is here reported for the first time for Picea mariana. New stilbene derivatives, piceasides O and P were also characterized herein as new isorhapontin dimers. This study provides novel information about the optimal extraction of polyphenols from black spruce bark, especially for highly bioactive stilbenes including the trans-resveratrol. Full article

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Open AccessFeature PaperReview

Resveratrol-Induced Effects on Body Fat Differ Depending on Feeding Conditions

by Iñaki Milton-Laskibar, Saioa Gómez-Zorita, Leixuri Aguirre, Alfredo Fernández-Quintela, Marcela González and María P. Portillo

Molecules 2017, 22(12), 2091; https://doi.org/10.3390/molecules22122091 - 29 Nov 2017

Cited by 9 | Viewed by 6244

Abstract

Science constantly seeks to identify new molecules that could be used as dietary functional ingredients in the fight against obesity and its co-morbidities. Among them, polyphenols represent a group of molecules of increasing interest. One of the most widely studied polyphenols is resveratrol [...] Read more.

Science constantly seeks to identify new molecules that could be used as dietary functional ingredients in the fight against obesity and its co-morbidities. Among them, polyphenols represent a group of molecules of increasing interest. One of the most widely studied polyphenols is resveratrol (trans-3,4′,5-trihydroxystilbene), which has been proposed as an “energy restriction mimetic” because it can exert energy restriction-like effects. The aim of this review is to analyze the effects of resveratrol on obesity under different feeding conditions, such as overfeeding, normal feeding, and energy restriction, in animals and humans. The vast majority of the studies reported have addressed the administration of resveratrol to animals alongside an obesogenic diet. Under these experimental conditions usually a decreased body weight amount was found. To date, studies that focus on the effects of resveratrol under normal feeding or energy restriction conditions in animals and humans are scarcer. In these studies no changes in body fat were reported. After analyzing the results obtained under overfeeding, normal feeding, and energy restriction conditions, it can be stated that resveratrol is useful in reducing body fat accumulation, and thus preventing obesity. Nevertheless, for ethical reasons, these results have been obtained in animals. By contrast, there are no evidences showing the usefulness of this phenolic compound in reducing previously accumulated body fat. Consequently, as of yet, there is not scientific support for proposing resveratrol as a new anti-obesity treatment tool. Full article

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Open AccessArticle

The Rosiglitazone-Like Effects of Vitexilactone, a Constituent from Vitex trifolia L. in 3T3-L1 Preadipocytes

by Atsuyoshi Nishina, Masaya Itagaki, Daisuke Sato, Hirokazu Kimura, Yasuaki Hirai, Nyunt Phay and Makoto Makishima

Molecules 2017, 22(11), 2030; https://doi.org/10.3390/molecules22112030 - 22 Nov 2017

Cited by 16 | Viewed by 5834

Abstract

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from [...] Read more.

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from Myanmar, induced adipogenesis similar to rosiglitazone (ROS), which is a TZD, in 3T3-L1 preadipocytes. In the present study, we attempted to isolate from V. trifolia those compounds that showed ROS-like effects. Among the extracts of hexane, ethyl acetate, and methanol obtained from V. trifolia, the ethyl acetate extract with the strongest ROS-like effects was purified by various chromatographic methods to obtain three known compounds: vitexilactone (1), vitexicarpin (2) and oleanolic acid (3). Among the isolated compounds, the ROS-like action of 1 was the strongest. The effects of 1 on 3T3-L1 cells during adipogenesis were compared with those of ROS. Both 1 and ROS increased lipid accumulation, the expression of adiponectin and GLUT4 in the cell membrane and decreased both the size of adipocytes and the phosphorylation of IRS-1, ERK1/2 and JNK in 3T3-L1 cells. In contrast, unlike ROS, the induction of proteins involved in lipogenesis was partial. ROS-like effects of 1 in 3T3-L1 cells were suppressed by the addition of bisphenol A diglycidyl ether (BADGE), one of a peroxisome proliferator-activated receptor γ (PPARγ) antagonists, suggesting that the action of 1 on adipocytes is mediated by PPARγ. From the results of the present study, it can be concluded that 1 is a novel insulin sensitizer candidate. Full article

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Open AccessArticle

Application of an Ultrafine Shearing Method for the Extraction of C-Phycocyanin from Spirulina platensis

by Jianfeng Yu

Molecules 2017, 22(11), 2023; https://doi.org/10.3390/molecules22112023 - 21 Nov 2017

Cited by 13 | Viewed by 6222

Abstract

Cell disruption is an important step during the extraction of C-phycocyanin from Spirulina platensis. An ultrafine shearing method is introduced and combined with soaking and ultrasonication to disrupt the cell walls of S. platensis efficiently and economically. Five kinds of cell disruption [...] Read more.

Cell disruption is an important step during the extraction of C-phycocyanin from Spirulina platensis. An ultrafine shearing method is introduced and combined with soaking and ultrasonication to disrupt the cell walls of S. platensis efficiently and economically. Five kinds of cell disruption method, including soaking, ultrasonication, freezing-thawing, soaking-ultrafine shearing and soaking-ultrafine shearing-ultrasonication were applied to break the cell walls of S. platensis. The effectiveness of cell breaking was evaluated based on the yield of the C-phycocyanin. The results show that the maximum C-phycocyanin yield was 9.02%, achieved by the soaking-ultrafine shearing-ultrasonication method, followed by soaking (8.43%), soaking-ultrafine shearing (8.89%), freezing and thawing (8.34%), and soaking-ultrasonication (8.62%). The soaking-ultrafine shearing-ultrasonication method is a novel technique for breaking the cell walls of S. platensis for the extraction of C-phycocyanin. Full article

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Open AccessArticle

Two Sulfur Glycoside Compounds Isolated from Lepidium apetalum Willd Protect NRK52e Cells against Hypertonic-Induced Adhesion and Inflammation by Suppressing the MAPK Signaling Pathway and RAAS

by Peipei Yuan, Xiaoke Zheng, Meng Li, Yingying Ke, Yang Fu, Qi Zhang, Xiaolan Wang and Weisheng Feng

Molecules 2017, 22(11), 1956; https://doi.org/10.3390/molecules22111956 - 12 Nov 2017

Cited by 14 | Viewed by 6547

Abstract

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e [...] Read more.

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺–K⁺ ATP content in renal medulla. After treatment with cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca²⁺ influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis-DG and trans-DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis-DG and trans-DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors. Full article

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Open AccessReview

Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism

by Michal Bijak

Molecules 2017, 22(11), 1942; https://doi.org/10.3390/molecules22111942 - 10 Nov 2017

Cited by 276 | Viewed by 23563

Abstract

Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not [...] Read more.

Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, which has been confirmed in various studies. This compound belongs to the flavonoid group known as flavonolignans. Silybin’s structure consists in two main units. The first is based on a taxifolin, the second a phenyllpropanoid unit, which in this case is conyferil alcohol. These two units are linked together into one structure by an oxeran ring. Since the 1970s, silybin has been regarded in official medicine as a substance with hepatoprotective properties. There is a large body of research that demonstrates silybin’s many other healthy properties, but there are still a lack of papers focused on its molecular structure, chemistry, metabolism, and novel form of administration. Therefore, the aim of this paper is a literature review presenting and systematizing our knowledge of the silybin molecule, with particular emphasis on its structure, chemistry, bioavailability, and metabolism. Full article

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Open AccessArticle

Antimicrobial Abietane-Type Diterpenoids from Plectranthus punctatus

by Negera Abdissa, Marcel Frese and Norbert Sewald

Molecules 2017, 22(11), 1919; https://doi.org/10.3390/molecules22111919 - 7 Nov 2017

Cited by 28 | Viewed by 5603

Abstract

Four new para-benzoquinone containing abietane-type diterpenoids (1–4) along with thirteen known diterpenoids (5–17) were isolated from the roots of Plectranthus punctatus. The structures of the compounds were established by detailed spectroscopic analyses and [...] Read more.

Four new para-benzoquinone containing abietane-type diterpenoids (1–4) along with thirteen known diterpenoids (5–17) were isolated from the roots of Plectranthus punctatus. The structures of the compounds were established by detailed spectroscopic analyses and comparison with literature data. The compounds were tested for their antibacterial and cytotoxic activity and showed significant inhibitory activity against all bacterial strains used, with compounds 6, 8, 10, and 11 showing an inhibition zone for Staphylococcus warneri even greater than the reference drug, gentamycin. Full article

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Open AccessArticle

Structural and Functional Properties Changes of β-Conglycinin Exposed to Hydroxyl Radical-Generating Systems

by Jing Xu, Zijing Chen, Dong Han, Yangyang Li, Xiaotong Sun, Zhongjiang Wang and Hua Jin

Molecules 2017, 22(11), 1893; https://doi.org/10.3390/molecules22111893 - 3 Nov 2017

Cited by 25 | Viewed by 4294

Abstract

The objective of the present study was to examine the structural and functional changes of β-conglycinin exposed to oxidizing radicals produced by FeCl₃/H₂O₂/ascorbic acid hydroxyl radical-generating system (HRGS) for 3 h at room temperature. Increasing H₂ [...] Read more.

The objective of the present study was to examine the structural and functional changes of β-conglycinin exposed to oxidizing radicals produced by FeCl₃/H₂O₂/ascorbic acid hydroxyl radical-generating system (HRGS) for 3 h at room temperature. Increasing H₂O₂ concentrations resulted in a loss of histidine residues, lysine residues, and available lysine, which was accompanied by the formation of protein carbonyls and disulphide bonds (p < 0.05). Changes in secondary structure, surface hydrophobicity, and intrinsic fluorescence indicated that hydroxyl radicals had induced protein unfolding and conformational alterations. Results from SDS-PAGE implied that a small amount of protein cross-linkages produced by oxidative incubation. The emulsifying properties of β-conglycinin were gradually improved with the increasing extent of oxidation. The structural changes above contributed to the reduction of potential allergenicity of β-conglycinin, as verified by specific ELISA analysis. These results suggest that moderate oxidation could partially improve the protein functional properties and reduced the potential allergy of protein, providing guidance for effective use of moderately oxidized soy protein in the industry. Full article

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Open AccessArticle

Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval))

by Lipeng Wu, Xin Huo, Xiaolong Zhou, Duoyong Zhao, Weizhong He, Shenghong Liu, Hejiang Liu, Ting Feng and Cheng Wang

Molecules 2017, 22(11), 1873; https://doi.org/10.3390/molecules22111873 - 1 Nov 2017

Cited by 33 | Viewed by 5898

Abstract

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme [...] Read more.

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval)) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides. Full article

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Open AccessArticle

Identification for the First Time of Cyclo(d-Pro-l-Leu) Produced by Bacillus amyloliquefaciens Y1 as a Nematocide for Control of Meloidogyne incognita

by Qaiser Jamal, Jeong-Yong Cho, Jae-Hak Moon, Shahzad Munir, Muhammad Anees and Kil Yong Kim

Molecules 2017, 22(11), 1839; https://doi.org/10.3390/molecules22111839 - 27 Oct 2017

Cited by 43 | Viewed by 5783

Abstract

The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 [...] Read more.

The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 to M. incognita significantly inhibited the hatching of eggs and caused the mortality of second-stage juveniles (J2), with these inhibitory effects depending on the length of incubation time and concentration of the treatment. The dipeptide cyclo(d-Pro-l-Leu) was identified in B. amyloliquefaciens culture for the first time using chromatographic techniques and nuclear magnetic resonance (NMR ¹H, ¹³C, H-H COSY, HSQC, and HMBC) and recognized to have nematocidal activity. Various concentrations of cyclo(d-Pro-l-Leu) were investigated for their effect on the hatching of eggs and J2 mortality. Moreover, the in vivo nematocidal activity of the Y1 strain was investigated by conducting pot experiments in which tomato plants were inoculated with M. incognita. Each and every pot was amended 50 mL of fertilizer media (F), or Y1 culture, or nematicide (N) (only once), or fertilizer media with N (FN) at 1, 2, 3, 4 and 5 weeks after transplantation. The results of the pot experiments demonstrated the antagonistic effect of B. amyloliquefaciens Y1 against M. incognita as it significantly decreases the count of eggs and galls per root of the tomato plant as well as the population of J2 in the soil. Besides, the investigation into the growth parameters, such as the length of shoot, shoot fresh and dry weights of the tomato plants, showed that they were significantly higher in the Y1 strain Y1-treated plants compared to F-, FN- and N-treated plants. Therefore, the biocontrol repertoire of this bacterium opens a new insight into the applications in crop pest control. Full article

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Open AccessArticle

Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate Hydrolyzing Enzymes by Nordic Berry Extracts

by Giang Thanh Thi Ho, Thi Kim Yen Nguyen, Eili Tranheim Kase, Margey Tadesse, Hilde Barsett and Helle Wangensteen

Molecules 2017, 22(10), 1806; https://doi.org/10.3390/molecules22101806 - 24 Oct 2017

Cited by 28 | Viewed by 6008

Abstract

A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. [...] Read more.

A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes. Full article

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Open AccessArticle

Equol, a Clinically Important Metabolite, Inhibits the Development and Pathogenicity of Magnaporthe oryzae, the Causal Agent of Rice Blast Disease

by Jiaoyu Wang, Ling Li, Yeshi Yin, Zhuokan Gu, Rongyao Chai, Yanli Wang and Guochang Sun

Molecules 2017, 22(10), 1799; https://doi.org/10.3390/molecules22101799 - 24 Oct 2017

Cited by 7 | Viewed by 6421

Abstract

Equol, a metabolite of soybean isoflavone daidzein, has been proven to have various bioactivities related to human health, but little is known on its antifungal activity to plant fungal pathogens. Magnaporthe oryzae is a phytopathogenic fungus that causes rice blast, a devastating disease [...] Read more.

Equol, a metabolite of soybean isoflavone daidzein, has been proven to have various bioactivities related to human health, but little is known on its antifungal activity to plant fungal pathogens. Magnaporthe oryzae is a phytopathogenic fungus that causes rice blast, a devastating disease on rice. Here, we demonstrated that equol influences the development and pathogenicity of M. oryzae. Equol showed a significant inhibition to the mycelial growth, conidial generation and germination, and appressorial formation of M. oryzae. As a result, equol greatly reduced the virulence of M. oryzae on rice and barley leaves. The antifungal activity of equol was also found in several other plant fungal pathogens. These findings expand our knowledge on the bioactivities of equol. Full article

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Open AccessArticle

Phenolic Compounds Present Schinus terebinthifolius Raddi Influence the Lowering of Blood Pressure in Rats

by Lorena De Lima Glória, Mariana Barreto de Souza Arantes, Silvia Menezes de Faria Pereira, Guilherme De Souza Vieira, Camilla Xavier Martins, Almir Ribeiro de Carvalho Junior, Fernanda Antunes, Raimundo Braz-Filho, Ivo José Curcino Vieira, Larissa Leandro da Cruz, Douglas Siqueira de Almeida Chaves, Silvério De Paiva Freitas and Daniela Barros de Oliveira

Molecules 2017, 22(10), 1792; https://doi.org/10.3390/molecules22101792 - 23 Oct 2017

Cited by 23 | Viewed by 5797

Abstract

This study identified two phenolic compounds in Schinus terebinthifolius Raddi fruits: naringenin (first report in this species) and gallic acid. Their structures were elucidated by nuclear magnetic resonance (NMR) data (¹H-, ¹³C-NMR) and a high-performance liquid chromatography (HPLC) technique. A [...] Read more.

This study identified two phenolic compounds in Schinus terebinthifolius Raddi fruits: naringenin (first report in this species) and gallic acid. Their structures were elucidated by nuclear magnetic resonance (NMR) data (¹H-, ¹³C-NMR) and a high-performance liquid chromatography (HPLC) technique. A high content of phenolics (659.21 mg of gallic acid equivalents/g of sample—Folin-Ciocalteau method) and total flavonoids (140.69 mg of rutin equivalents/g of sample—aluminum chloride method) were quantified in S. terebinthifolius, as well as high antioxidant activity (77.47%—2,2-diphenyl-1-picrylhydrazyl, DPPH method). The antihypertensive activity related to its phenolic content was investigated. After intravenous infusion in Wistar rats, these phenolics significantly reduced (p < 0.05) the systolic, median, and diastolic arterial pressures of individuals. The rotarod test was performed to determine the mechanism of action of the sample vasorelaxant effect. It was found that its action exceeded that of the positive control used (diazepam). This confirmed the vasodilatory activity exerted by S. terebinthifolius fruits is related to the phenolic compounds present in the plant, which are potent antioxidants and inhibit oxidative stress, mainly in the central nervous system. Full article

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Open AccessArticle

Structure, Absolute Configuration, and Antiproliferative Activity of Abietane and Icetexane Diterpenoids from Salvia ballotiflora

by Baldomero Esquivel, Celia Bustos-Brito, Mariano Sánchez-Castellanos, Antonio Nieto-Camacho, Teresa Ramírez-Apan, Pedro Joseph-Nathan and Leovigildo Quijano

Molecules 2017, 22(10), 1690; https://doi.org/10.3390/molecules22101690 - 18 Oct 2017

Cited by 26 | Viewed by 6535

Abstract

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1–5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and ¹³C-NMR, [...] Read more.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1–5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and ¹³C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (μM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (μM) = 0.0.46 ± 0.05 and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (μM) = 0.08 ± 0.003 and 0.05 ± 0.003, as the positive control), respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 μmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as the positive control (IC₅₀ (μM) = 31.7 ± 1.04). The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae. Full article

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Open AccessArticle

Health-Promoting Phytochemicals from 11 Mustard Cultivars at Baby Leaf and Mature Stages

by Marissa D. Frazie, Moo Jung Kim and Kang-Mo Ku

Molecules 2017, 22(10), 1749; https://doi.org/10.3390/molecules22101749 - 17 Oct 2017

Cited by 41 | Viewed by 9286

Abstract

Mustard is a Brassica vegetable that provides a number of phytonutrients. However, the phytonutrient profile of mustard has been relatively limited. We analyzed the glucosinolates and their hydrolysis products, carotenoids, total anthocyanin and phenolic contents, and antioxidant capacity of the leaves of 11 [...] Read more.

Mustard is a Brassica vegetable that provides a number of phytonutrients. However, the phytonutrient profile of mustard has been relatively limited. We analyzed the glucosinolates and their hydrolysis products, carotenoids, total anthocyanin and phenolic contents, and antioxidant capacity of the leaves of 11 mustard cultivars grown in a greenhouse at the baby leaf and mature stages. An aliphatic glucosinolate sinigrin and its hydrolysis products allyl isothiocyanate and 1-cyano-2,3-epithiopropane were the major phytonutrients in the mustard leaves. Carotenoids β-carotene, lutein, violaxanthin, and neoxanthin were detected. We found phytonutrient concentration and their change with plant growth were cultivar-dependent. The %RDA value for vitamin A calculated using β-carotene content and retinol activity equivalents suggests that mustard cultivars used in this study can be a good source of vitamin A. Phenolic contents and antioxidant capacity also varied among cultivars and between physiological stages. Our results suggest that mustard leaves are rich in various phytochemicals and their composition depends on cultivar and the physiological stage. This is the first report on phytochemical composition in various mustard cultivars at different physiological stages. Full article

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Open AccessArticle

Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC-TQ/MS

by Yi Jin, Yu-Ping Tang, Zhen-Hua Zhu, Er-Xin Shang, Han-Qing Pang, Xu-Qin Shi, Yan-Yan Chen, Jin Wang, Xing Chang, An Kang, Gui-Sheng Zhou, Ya-Jun Shi, Jin Sun, Zhi-Shu Tang, Shao-Ping Li and Jin-Ao Duan

Molecules 2017, 22(10), 1746; https://doi.org/10.3390/molecules22101746 - 17 Oct 2017

Cited by 18 | Viewed by 5240

Abstract

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, [...] Read more.

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK) behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the C_max and AUC_0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae. Full article

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Open AccessArticle

Electrospun Phospholipid Fibers as Micro-Encapsulation and Antioxidant Matrices

by Elhamalsadat Shekarforoush, Ana C. Mendes, Vanessa Baj, Sophie R. Beeren and Ioannis S. Chronakis

Molecules 2017, 22(10), 1708; https://doi.org/10.3390/molecules22101708 - 17 Oct 2017

Cited by 26 | Viewed by 6107

Abstract

Electrospun phospholipid (asolectin) microfibers were investigated as antioxidants and encapsulation matrices for curcumin and vanillin. These phospholipid microfibers exhibited antioxidant properties which increased after the encapsulation of both curcumin and vanillin. The total antioxidant capacity (TAC) and the total phenolic content (TPC) of [...] Read more.

Electrospun phospholipid (asolectin) microfibers were investigated as antioxidants and encapsulation matrices for curcumin and vanillin. These phospholipid microfibers exhibited antioxidant properties which increased after the encapsulation of both curcumin and vanillin. The total antioxidant capacity (TAC) and the total phenolic content (TPC) of curcumin/phospholipid and vanillin/phospholipid microfibers remained stable over time at different temperatures (refrigerated, ambient) and pressures (vacuum, ambient). ¹H-NMR confirmed the chemical stability of both encapsulated curcumin and vanillin within phospholipid fibers. Release studies in aqueous media revealed that the phenolic bioactives were released mainly due to swelling of the phospholipid fiber matrix over time. The above studies confirm the efficacy of electrospun phospholipid microfibers as encapsulation and antioxidant systems. Full article

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Open AccessReview

A Review on the Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Geniposide, a Natural Product

by Mingqiu Shan, Sheng Yu, Hui Yan, Sheng Guo, Wei Xiao, Zhenzhong Wang, Li Zhang, Anwei Ding, Qinan Wu and Sam Fong Yau Li

Molecules 2017, 22(10), 1689; https://doi.org/10.3390/molecules22101689 - 10 Oct 2017

Cited by 89 | Viewed by 10486

Abstract

Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C₁₇H₂₄O₁₀) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its [...] Read more.

Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C₁₇H₂₄O₁₀) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its natural derivatives have also been isolated and characterized by researchers. Furthermore, a large body of pharmacological evidence has proved the various biological activities of geniposide, such as anti-inflammatory, anti-oxidative, anti-diabetic, neuroprotective, hepatoprotective, cholagogic effects and so on. However, there have been some research articles on its toxicity in recent years. Therefore, this review paper aims to provide the researchers with a comprehensive profile of geniposide on its phytochemistry, pharmacology, pharmacokinetics and toxicology in order to highlight some present issues and future perspectives as well as to help us develop and utilize this iridoid glycoside more efficiently and safely. Full article

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Open AccessArticle

Bioassay-Guided Isolated Compounds from Morinda officinalis Inhibit Alzheimer’s Disease Pathologies

by Yoon Kyoung Lee, Hyo Jeong Bang, Jeong Bin Oh and Wan Kyunn Whang

Molecules 2017, 22(10), 1638; https://doi.org/10.3390/molecules22101638 - 29 Sep 2017

Cited by 36 | Viewed by 6529

Abstract

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, [...] Read more.

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, M. officinalis has not been evaluated in an AD bioassay. Therefore, M. officinalis extracts and fractions were tested for AD-related activity, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. A bioassay-guided approach led to isolation of 10 active compounds, eight anthraquinones (1–8), one coumarin (9), and one phytosterol (10), from n-hexane and ethyl acetate fractions of M. officinalis. The five anthraquinones (4–8) were stronger inhibitors of AChE than were other compounds. Compounds 3 and 9 were good inhibitors of BChE, and compounds 3 and 8 were good inhibitors of BACE1. Compounds 1–5 and 7–9 were more active than the positive control in inhibiting AGE formation. In addition, we first suggested a structure-activity relationship by which anthraquinones inhibit AChE and BACE1. Our findings demonstrate the preventive and therapeutic efficacy of M. officinalis for AD and its potential use as a natural alternative medicine. Full article

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Open AccessArticle

In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis

by Dan Cheng, Ghualm Murtaza, Suya Ma, Lingling Li, Xinjie Li, Fangze Tian, Junchao Zheng and Yi Lu

Molecules 2017, 22(10), 1614; https://doi.org/10.3390/molecules22101614 - 26 Sep 2017

Cited by 24 | Viewed by 8138

Abstract

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that [...] Read more.

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression. Methods: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin. Results: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression. Conclusions: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway. Full article

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Open AccessCommunication

Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells

by Seulah Lee, Dahae Lee, Tae Su Jang, Ki Sung Kang, Joo-Won Nam, Hae-Jeung Lee and Ki Hyun Kim

Molecules 2017, 22(10), 1583; https://doi.org/10.3390/molecules22101583 - 21 Sep 2017

Cited by 39 | Viewed by 6947

Abstract

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 [...] Read more.

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (1–3), a sesquiterpene (4), two steroids (5–6), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 1–3 had IC₅₀ values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds 1–3 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 1–3 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 1–3 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 1–3 could be promising lead compounds for the development of novel anti-inflammatory agents. Full article

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Open AccessReview

Cardiovascular Activity of the Chemical Constituents of Essential Oils

by Tadeu Uggere De Andrade, Girlandia Alexandre Brasil, Denise Coutinho Endringer, Flávio Rogério Da Nóbrega and Damião Pergentino De Sousa

Molecules 2017, 22(9), 1539; https://doi.org/10.3390/molecules22091539 - 17 Sep 2017

Cited by 28 | Viewed by 8170

Abstract

Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this [...] Read more.

Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this group of natural products because of their effects on the cardiovascular system. The pharmacological data indicate a therapeutic potential for essential oils for use in the treatment of cardiovascular diseases. Therefore, this review reports the current studies of essential oils chemical constituents with cardiovascular activity, including a description of their mechanisms of action. Full article

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Open AccessCommunication

A New Monoterpene from the Leaves of a Radiation Mutant Cultivar of Perilla frutescens var. crispa with Inhibitory Activity on LPS-Induced NO Production

by Bomi Nam, Yangkang So, Hyo-Young Kim, Jin-Baek Kim, Chang Hyun Jin and Ah-Reum Han

Molecules 2017, 22(9), 1471; https://doi.org/10.3390/molecules22091471 - 4 Sep 2017

Cited by 16 | Viewed by 5443

Abstract

The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group [...] Read more.

The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group resulted in the development of a new perilla cultivar, P. frutescens var. crispa (cv. Antisperill; PFCA), which has a higher content of isoegomaketone. The leaves of PFCA were extracted by supercritical carbon dioxide (SC-CO₂) extraction, and phytochemical investigation on this extract led to the isolation and identification of a new compound, 9-hydroxy-isoegomaketone [(2E)-1-(3-furanyl)-4-hydroxy-4-methyl-2-penten-1-one; 1]. Compound 1 exhibited inhibitory activity on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with an IC₅₀ value of 14.4 μM. The compounds in the SC-CO₂ extracts of the radiation mutant cultivar and the original plant were quantified by high-performance liquid chromatography with diode array detection. Full article

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Open AccessArticle

Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells

by Ashraf B. Abdel-Naim, Abdullah A. Alghamdi, Mardi M. Algandaby, Fahad A. Al-Abbasi, Ahmed M. Al-Abd, Hossam M. Abdallah, Ali M. El-Halawany and Masao Hattori

Molecules 2017, 22(9), 1467; https://doi.org/10.3390/molecules22091467 - 4 Sep 2017

Cited by 11 | Viewed by 5880

Abstract

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane [...] Read more.

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells. Full article

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Open AccessArticle

Soluble Epoxide Hydrolase Inhibitory Activity of Components Isolated from Apios americana Medik

by Jang Hoon Kim, Hyo Young Kim, Si Yong Kang, Young Ho Kim and Chang Hyun Jin

Molecules 2017, 22(9), 1432; https://doi.org/10.3390/molecules22091432 - 30 Aug 2017

Cited by 11 | Viewed by 4963

Abstract

A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (2–8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, [...] Read more.

A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (2–8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 μM. The respective competitive (1) and mixed (2) inhibitors were revealed to have K_i values of 21.0 ± 0.8 and 14.5 ± 1.5 μM, based on the Dixon plot. The potential inhibitor (2) was visually presented in a predicted binding pose in the receptor by molecular docking. Additionally, molecular dynamics were performed for a detailed understanding of their complex by Gromacs 4.6.5 package. Full article

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Open AccessReview

An Overview of LEDs’ Effects on the Production of Bioactive Compounds and Crop Quality

by Md. Mohidul Hasan, Tufail Bashir, Ritesh Ghosh, Sun Keun Lee and Hanhong Bae

Molecules 2017, 22(9), 1420; https://doi.org/10.3390/molecules22091420 - 27 Aug 2017

Cited by 147 | Viewed by 12085

Abstract

Light-emitting diodes (LEDs) are characterized by their narrow-spectrum, non-thermal photon emission, greater longevity, and energy-saving characteristics, which are better than traditional light sources. LEDs thus hold the potential to revolutionize horticulture lighting technology for crop production, protection, and preservation. Exposure to different LED [...] Read more.

Light-emitting diodes (LEDs) are characterized by their narrow-spectrum, non-thermal photon emission, greater longevity, and energy-saving characteristics, which are better than traditional light sources. LEDs thus hold the potential to revolutionize horticulture lighting technology for crop production, protection, and preservation. Exposure to different LED wavelengths can induce the synthesis of bioactive compounds and antioxidants, which in turn can improve the nutritional quality of horticultural crops. Similarly, LEDs increase the nutrient contents, reduce microbial contamination, and alter the ripening of postharvest fruits and vegetables. LED-treated agronomic products can be beneficial for human health due to their good nutrient value and high antioxidant properties. Besides that, the non-thermal properties of LEDs make them easy to use in closed-canopy or within-canopy lighting systems. Such configurations minimize electricity consumption by maintaining optimal incident photon fluxes. Interestingly, red, blue, and green LEDs can induce systemic acquired resistance in various plant species against fungal pathogens. Hence, when seasonal clouds restrict sunlight, LEDs can provide a controllable, alternative source of selected single or mixed wavelength photon source in greenhouse conditions. Full article

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Open AccessArticle

Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity

by Armando Escobar-Ramos, Carlos Ernesto Lobato-García, Alejandro Zamilpa, Abraham Gómez-Rivera, Jaime Tortoriello and Manasés González-Cortazar

Molecules 2017, 22(9), 1405; https://doi.org/10.3390/molecules22091405 - 24 Aug 2017

Cited by 19 | Viewed by 5613

Abstract

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: [...] Read more.

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1); 3-deoxysappanchalcone (2); three homoisoflavonoids known as hematoxylol A (3); 4-O-methylhematoxylol (4); and, hematoxin (5). The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum), and allowed to demonstrate that the methanolic extract (EC₅₀ = 62.11 ± 3.23) fractions HcF7 (EC₅₀ = 61.75 ± 3.55) and HcF9 (EC₅₀ = 125.5 ± 10.65) and compounds 1 (EC₅₀ = 16.06 ± 2.15) and 2 (EC₅₀ = 25.37 ± 3.47) of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC₅₀ = 20.08 ± 2.0) as a positive control. Full article

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Open AccessArticle

Chemical Constituents of Murraya tetramera Huang and Their Repellent Activity against Tribolium castaneum

by Chun-Xue You, Shan-Shan Guo, Wen-Juan Zhang, Zhu-Feng Geng, Jun-Yu Liang, Ning Lei, Shu-Shan Du and Zhi-Wei Deng

Molecules 2017, 22(8), 1379; https://doi.org/10.3390/molecules22081379 - 20 Aug 2017

Cited by 12 | Viewed by 5003

Abstract

Sixteen compounds were isolated from the leaves and stems of Murraya tetramera Huang. Based on the NMR and MS spectral results, the structures were determined. It was confirmed that the isolated compounds included three new compounds (9, 10 and 13) [...] Read more.

Sixteen compounds were isolated from the leaves and stems of Murraya tetramera Huang. Based on the NMR and MS spectral results, the structures were determined. It was confirmed that the isolated compounds included three new compounds (9, 10 and 13) and one new natural product (8), which were identified asmurratetra A (9), murratetra B (10), murratetra C (13) and [2-(7-methoxy-2-oxochromen-8-yl)-3-methylbut-2-enyl]3-methylbut-2-enoate (8), respectively. Meanwhile, the repellent activity against Tribolium castaneum was investigated for 13 of these isolated compounds. The results showed that the tested compounds had various levels of repellent activity against T. castaneum. Among them, compounds 1 (4(15)-eudesmene-1β,6α-diol), 11 (isoferulic acid) and 16 (2,3-dihydroxypropyl hexadecanoate) showed fair repellent activity against T. castaneum. They might be considered as potential leading compounds for the development of natural repellents. Full article

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Open AccessArticle

Portuguese Honeys from Different Geographical and Botanical Origins: A 4-Year Stability Study Regarding Quality Parameters and Antioxidant Activity

by Sonia Soares, Diana Pinto, Francisca Rodrigues, Rita C. Alves and M. Beatriz P.P. Oliveira

Molecules 2017, 22(8), 1338; https://doi.org/10.3390/molecules22081338 - 11 Aug 2017

Cited by 32 | Viewed by 5258

Abstract

Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L*, a*, b*) and antioxidant profile (total phenolics content, total flavonoids content, DPPH• scavenging activity, and ferric reducing [...] Read more.

Portuguese honeys (n = 15) from different botanical and geographical origins were analysed regarding their quality parameters (diastase activity, hydroxymethylfurfural content, moisture and pH), colour (L*, a*, b*) and antioxidant profile (total phenolics content, total flavonoids content, DPPH• scavenging activity, and ferric reducing power). The samples were analysed fresh and after 4-years of storage (at 25 °C and protected from light). The hydroxymethylfurfural content and diastase activity of the fresh samples were in accordance with the recommended values described in the legislation. In general, the antioxidant activity of the samples correlated more with the bioactive compounds content than with colour. The storage affected differently each individual sample, especially regarding the antioxidant profile. Nevertheless, although in general the lightness of the samples decreased (and the redness increased), after 4 years, 11 samples still presented acceptable diastase activity and hydroxymethylfurfural values. Full article

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Open AccessArticle

Identification and Biological Evaluation of Secondary Metabolites from Marine Derived Fungi-Aspergillus sp. SCSIOW3, Cultivated in the Presence of Epigenetic Modifying Agents

by Xiaofan Li, Zhenyao Xia, Jianqiang Tang, Jiahui Wu, Jing Tong, Mengjie Li, Jianhua Ju, Huirong Chen and Liyan Wang

Molecules 2017, 22(8), 1302; https://doi.org/10.3390/molecules22081302 - 4 Aug 2017

Cited by 45 | Viewed by 5990

Abstract

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW3, resulting in significant changes of the secondary metabolites. One new diphenylether-O-glycoside (diorcinol 3-O-α-D-ribofuranoside), along with seven known compounds, were isolated from the culture treated with a [...] Read more.

Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW3, resulting in significant changes of the secondary metabolites. One new diphenylether-O-glycoside (diorcinol 3-O-α-D-ribofuranoside), along with seven known compounds, were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). Compounds 2 and 4 exhibited significant biomembrane protective effect of erythrocytes. 2 also showed algicidal activity against Chattonella marina, a bloom forming alga responsible for large scale fish deaths. Full article

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Open AccessArticle

Immunomodulatory Activity of Octenyl Succinic Anhydride Modified Porang (Amorphophallus oncophyllus) Glucomannan on Mouse Macrophage-Like J774.1 Cells and Mouse Primary Peritoneal Macrophages

by Sellen Gurusmatika, Kosuke Nishi, Eni Harmayani, Yudi Pranoto and Takuya Sugahara

Molecules 2017, 22(7), 1187; https://doi.org/10.3390/molecules22071187 - 15 Jul 2017

Cited by 11 | Viewed by 7136

Abstract

Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the [...] Read more.

Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the phagocytosis activity of macrophage-like J774.1 cells and mouse peritoneal macrophages. In addition, OSA-PG increased the production of IL-6 and TNF-α by enhancing their gene expression. Immunoblot analysis displayed that OSA-PG tended to activate both nuclear factor-κB and mitogen-activated protein kinase cascades. Treatment of OSA-PG with polymyxin B revealed that cytokine production induced by OSA-PG was not caused by endotoxin contamination. Our findings also indicated that OSA-PG activates macrophages through not only Toll-like receptor (TLR) 4, but another receptor. Overall findings suggested that OSA-PG has a potential as an immunomodulatory food factor by stimulating macrophages. Full article

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Isolation and Characterization of Aphidicolin Derivatives from Tolypocladium inflatum

by Jie Lin, Shubin Niu, Zhengfeng Ding, Renlei Wang, Qun Dai, Wei Wei, Rongrong Luo and Ling Liu

Molecules 2017, 22(7), 1168; https://doi.org/10.3390/molecules22071168 - 12 Jul 2017

Cited by 11 | Viewed by 5188

Abstract

Inflatin G (1), a new aphidicolin analogue, together with seven known compounds inflatin A (2), inflatin B (3), aphidicolin (4), aphidicolin-17-monoacetate (5), gulypyrone A (6), pyridoxatin rotamers A (7) [...] Read more.

Inflatin G (1), a new aphidicolin analogue, together with seven known compounds inflatin A (2), inflatin B (3), aphidicolin (4), aphidicolin-17-monoacetate (5), gulypyrone A (6), pyridoxatin rotamers A (7) and B (8), were isolated from the ascomycete fungus Tolypocladium inflatum. Their structures were determined through NMR analyses and the circular dichroism data of the in situ formed [Rh₂(OCOCF₃)₄] complexes. Compounds 1, 4, 5, 7, and 8 showed modest cytotoxicity against four human cancer cell lines A549, CNE1-MP1, A375, and MCF-7. Full article

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2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway

by Jeong-Hyeon Ko, Jae Hwi Lee, Sang Hoon Jung, Seok-Geun Lee, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Woong Mo Yang, Jae-Young Um, Gautam Sethi and Kwang Seok Ahn

Molecules 2017, 22(7), 1157; https://doi.org/10.3390/molecules22071157 - 11 Jul 2017

Cited by 25 | Viewed by 6241

Abstract

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects [...] Read more.

2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma. Full article

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Cytotoxic Compounds from Aloe megalacantha

by Negera Abdissa, Sebastian Gohlke, Marcel Frese and Norbert Sewald

Molecules 2017, 22(7), 1136; https://doi.org/10.3390/molecules22071136 - 7 Jul 2017

Cited by 17 | Viewed by 5679

Abstract

Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along [...] Read more.

Phytochemical investigation of the ethyl acetate extract of the roots of Aloe megalacantha led to the isolation of four new natural products—1,8-dimethoxynepodinol (1), aloesaponarin III (2), 10-O-methylchrysalodin (3) and methyl-26-O-feruloyl-oxyhexacosanate (4)—along with ten known compounds. All purified metabolites were characterized by NMR, mass spectrometric analyses and comparison with literature data. The isolates were evaluated for their cytotoxic activity against a human cervix carcinoma cell line KB-3-1 and some of them exhibited good activity, with aloesaponarin II (IC₅₀ = 0.98 µM) being the most active compound. Full article

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Anti-Inflammatory and Anti-Urolithiasis Effects of Polyphenolic Compounds from Quercus gilva Blume

by Sung Hye Youn, Joo Hee Kwon, Jun Yin, Le Thi Tam, Hye Shin Ahn, Soon Chul Myung and Min Won Lee

Molecules 2017, 22(7), 1121; https://doi.org/10.3390/molecules22071121 - 5 Jul 2017

Cited by 16 | Viewed by 7666

Abstract

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include [...] Read more.

Quercus gilva Bume (QGB, family Fagaceae) is a tall evergreen oak species tree that grows in warm temperate regions in Korea, Japan, China and Taiwan. Quercus plants have long been the basis of traditional medicines. Their clinical benefits according to traditional medicine include relief of urolithiasis, tremors and inflammation. In the present study, the anti-urolithiasis activity including anti-inflammatory and anti-oxidative activities, of some phenolic compounds isolated from QGB were described. Seven compounds were isolated and identified as picraquassioside D (1), quercussioside (2), (+)-lyoniresinol-9′α-O-β-d-xylopyranoside (3), (+)-catechin (4), (−)-epicatechin (5), procyanidin B-3 (6), and procyanidin B-4 (7). Compounds 5–7 showed potent anti-oxidative and anti-inflammatory activities. These compounds were further tested for their inhibition of the gene expression of the inflammatory cytokines. The three compounds 5–7 showed dose-dependent inhibitory activities on gene expression of COX-2 and IL-1β. In vivo, urolithiasis was induced more effectively in an animal model of acute urolithiasis by the administration of QGB extract. These results indicate the potential of compounds from QGB in the treatment of urolithiasis. Full article

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Antioxidant Capacity, Anticancer Ability and Flavonoids Composition of 35 Citrus (Citrus reticulata Blanco) Varieties

by Yue Wang, Jing Qian, Jinping Cao, Dengliang Wang, Chunrong Liu, Rongxi Yang, Xian Li and Chongde Sun

Molecules 2017, 22(7), 1114; https://doi.org/10.3390/molecules22071114 - 5 Jul 2017

Cited by 108 | Viewed by 9551

Abstract

Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus [...] Read more.

Citrus (Citrus reticulate Blanco) is one of the most commonly consumed and widely distributed fruit in the world, which is possessing extensive bioactivities. Present study aimed to fully understand the flavonoids compositions, antioxidant capacities and in vitro anticancer abilities of different citrus resources. Citrus fruits of 35 varieties belonging to 5 types (pummelos, oranges, tangerines, mandarins and hybrids) were collected. Combining li quid chromatography combined with electrospray ionization mass spectrometry (LC-ESI-MS/MS) and ultra-performance liquid chromatography combined with diode array detector (UPLC-DAD), a total of 39 flavonoid compounds were identified, including 4 flavones, 9 flavanones and 26 polymethoxylated flavonoids (PMFs). Each citrus fruit was examined and compared by 4 parts, flavedo, albedo, segment membrane and juice sacs. The juice sacs had the lowest total phenolics, following by the segment membrane. Four antioxidant traits including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and cupric reducing antioxidant capacity (CUPRAC) were applied for the antioxidant capacities evaluation. Three gastric cancer cell lines, SGC-7901, BGC-823 and AGS were applied for the cytotoxicity evaluation. According to the results of correlation analysis, phenolics compounds might be the main contributor to the antioxidant activity of citrus extracts, while PMFs existing only in the flavedo might be closely related to the gastric cancer cell line cytotoxicity of citrus extracts. The results of present study might provide a theoretical guidance for the utilization of citrus resources. Full article

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Phytochemical Analysis and Antimicrobial Activity of Myrcia tomentosa (Aubl.) DC. Leaves

by Fabyola Amaral Da Silva Sa, Joelma Abadia Marciano De Paula, Pierre Alexandre Dos Santos, Leandra De Almeida Ribeiro Oliveira, Gerlon De Almeida Ribeiro Oliveira, Luciano Morais Liao, Jose Realino De Paula and Maria Do Rosario Rodrigues Silva

Molecules 2017, 22(7), 1100; https://doi.org/10.3390/molecules22071100 - 4 Jul 2017

Cited by 35 | Viewed by 6522

Abstract

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and [...] Read more.

This work describes the isolation and structural elucidation of compounds from the leaves of Myrcia tomentosa (Aubl.) DC. (goiaba-brava) and evaluates the antimicrobial activity of the crude extract, fractions and isolated compounds against bacteria and fungi. Column chromatography was used to fractionate and purify the extract of the M. tomentosa leaves and the chemical structures of the compounds were determined using spectroscopic techniques. The antibacterial and antifungal activities were assessed using the broth microdilution method. The phytochemical investigation isolated 11 compounds: α-bisabolol, α-bisabolol oxide B, α-cadinol, β-sitosterol, n-pentacosane, n-tetracosane, quercetin, kaempferol, avicularin, juglanin and guaijaverin. The crude ethanolic extract and its fractions were tested against 15 bacteria and 9 yeasts. The crude extract inhibited the in vitro growth of yeasts at concentration of 4 to 32 μg/mL. The hexane, dichloromethane, ethyl acetate and aqueous fractions inhibited Candida sp. at concentrations of 4 to 256 μg/mL, whereas the Cryptococcus sp. isolates were inhibited only by the hexane and dichloromethane fractions in minimal inhibitory concentrations (MICs) at 16 to 64 μg/mL. The flavonoid quercetin-3-O-α-arabinofuranose (avicularin) was the most active compound, inhibiting Candida species in concentrations of 2 to 32 μg/mL. The MIC values suggest potential activity of this plant species against yeast. Full article

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Antibacterial Activities of Pyrenylated Coumarins from the Roots of Prangos hulusii

by Nur Tan, Seçil Yazıcı-Tütüniş, Merve Bilgin, Emir Tan and Mahmut Miski

Molecules 2017, 22(7), 1098; https://doi.org/10.3390/molecules22071098 - 1 Jul 2017

Cited by 70 | Viewed by 6595

Abstract

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The [...] Read more.

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The root extract and its prenylated coumarins exhibit antimicrobial activity against nine standard and six clinically isolated strains at a concentration between 5 and 125 µg/mL. In particular, the new coumarin, 4′-senecioiloxyosthol (1), displayed 5 µg/mL MIC (Minimum Inhibitory Concentration) value against Bacillus subtilis ATCC 9372, murraol (4) and auraptenol (5) showed 63 µg/mL MIC value against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 9372, and isoimperatorin (9) exhibited 16 µg/mL MIC value. Full article

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Cell-Free Production of Pentacyclic Triterpenoid Compound Betulinic Acid from Betulin by the Engineered Saccharomyces cerevisiae

by Jianan Wu, Yongwu Niu, Abdelmoneim Bakur, Hao Li and Qihe Chen

Molecules 2017, 22(7), 1075; https://doi.org/10.3390/molecules22071075 - 27 Jun 2017

Cited by 13 | Viewed by 6222

Abstract

Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to [...] Read more.

Betulinic acid is a product of plant secondary metabolism which has shown various bioactivities. Several CYP716A subfamily genes were recently characterized encoding multifunctional oxidases capable of C-28 oxidation. CYP716A12 was identified as betulin C-28 oxidase, capable of modifying betulin. This study aimed to induce the transformation of betulin to betulinic acid by co-expressing enzymes CYP716A12 from Medicago truncatula and ATR1 from Arabidopsis thaliana in Saccharomyces cerevisiae. The microsome protein extracted from the transgenic yeast successfully catalyzed the transformation of betulin to betulinic acid. We also characterized the optimization of cell fragmentation, protein extraction method, and the conversion conditions. Response surface methodology was implemented, and the optimal yield of betulinic acid reached 18.70%. After optimization, the yield and the conversion rate of betulin were increased by 83.97% and 136.39%, respectively. These results may present insights and strategies for the sustainable production of betulinic acid in multifarious transgenic microbes. Full article

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Labradorins with Antibacterial Activity Produced by Pseudomonas sp.

by Anders Broberg, Joakim Bjerketorp, Pierre Andersson, Christer Sahlberg and Jolanta J. Levenfors

Molecules 2017, 22(7), 1072; https://doi.org/10.3390/molecules22071072 - 27 Jun 2017

Cited by 9 | Viewed by 8427

Abstract

The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) [...] Read more.

The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 μg·mL⁻¹ and 50 μg·mL⁻¹, respectively, whereas the MICs against A. baumannii were >50 μg·mL⁻¹. The CC₅₀ values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 μg·mL⁻¹ and 20 μg·mL⁻¹, respectively, and for compound 2 were >100 μg·mL⁻¹ and 20 μg·mL⁻¹, respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics. Full article

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Deoxyelephantopin and Isodeoxyelephantopin as Potential Anticancer Agents with Effects on Multiple Signaling Pathways

by Tahir Mehmood, Amara Maryam, Hamed A. Ghramh, Muhammad Khan and Tonghui Ma

Molecules 2017, 22(6), 1013; https://doi.org/10.3390/molecules22061013 - 21 Jun 2017

Cited by 30 | Viewed by 7035

Abstract

Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and [...] Read more.

Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of “Elephantopus scaber and Elephantopus carolinianus”, traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation. Recently, the anticancer activity of DET and IDET has been widely investigated. Here, our aim is to review the current status of DET and IDET, and discuss their anticancer activity with specific emphasis on molecular targets and mechanisms used by these compounds to trigger apoptosis pathways which may help to further design and conduct research to develop them as lead therapeutic drugs for cancer treatments. The literature has shown that DET and IDET induce apoptosis through multiple signaling pathways which are deregulated in cancer cells and suggested that by targeting multiple pathways simultaneously, these compounds could selectively kill cancer cells. This review suggests that DET and IDET hold promising anticancer activity but additional studies and clinical trials are needed to validate and understand their therapeutic effect to develop them into potent therapeutics for the treatment of cancer. Full article

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Phenolic Glycosides from Capsella bursa-pastoris (L.) Medik and Their Anti-Inflammatory Activity

by Joon Min Cha, Won Se Suh, Tae Hyun Lee, Lalita Subedi, Sun Yeou Kim and Kang Ro Lee

Molecules 2017, 22(6), 1023; https://doi.org/10.3390/molecules22061023 - 20 Jun 2017

Cited by 28 | Viewed by 9106

Abstract

A new sesquilignan glycoside 1, together with seven known phenolic glycosides 2–8 were isolated from the aerial parts of Capsella bursa-pastoris. The chemical structure of the new compound 1 was elucidated by extensive nuclear magnetic resonance (NMR) data (¹ [...] Read more.

A new sesquilignan glycoside 1, together with seven known phenolic glycosides 2–8 were isolated from the aerial parts of Capsella bursa-pastoris. The chemical structure of the new compound 1 was elucidated by extensive nuclear magnetic resonance (NMR) data (¹H- and ¹³C-NMR, ¹H-¹H correlation spectroscopy (¹H-¹H COSY), heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and nuclear overhauser effect spectroscopy (NOESY)) and HR-FABMS analysis. The anti-inflammatory effects of 1–8 were evaluated in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Compounds 4 and 7 exhibited moderate inhibitory effects on nitric oxide production in LPS-activated BV-2 cells, with IC₅₀ values of 17.80 and 27.91 µM, respectively. Full article

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Anti-Inflammatory Phenolic Acid Esters from the Roots and Rhizomes of Notopterygium incisium and Their Permeability in the Human Caco-2 Monolayer Cell Model

by Xiu-Wen Wu, Wei Wei, Xiu-Wei Yang, You-Bo Zhang, Wei Xu, Yan-Fang Yang, Guo-Yue Zhong, Hong-Ning Liu and Shi-Lin Yang

Molecules 2017, 22(6), 935; https://doi.org/10.3390/molecules22060935 - 4 Jun 2017

Cited by 31 | Viewed by 6247

Abstract

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2–9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated [...] Read more.

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2–9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. 4-Methoxyphenethyl ferulate (8) NMR data is reported here for the first time. The uptake and transepithelial transport of the isolated compounds 1–9 were investigated in the human intestinal Caco-2 cell monolayer model. Compounds 2 and 6 were assigned for the well-absorbed compounds, compound 8 was assigned for the moderately absorbed compound, and compounds 1, 3, 4, 5, 7, and 9 were assigned for the poorly absorbed compounds. Moreover, all of the isolated compounds were assayed for the inhibitory effects against nitric oxide (NO) production in the lipopolysaccharide-activated RAW264.7 macrophages model and L-N⁶-(1-iminoethyl)-lysine (L-NIL) was used as a positive control. Compounds 1, 5, 8, and 9 exhibited potent inhibitory activity on NO production with the half maximal inhibitory concentration (IC₅₀) values of 1.01, 4.63, 2.47, and 2.73 μM, respectively, which were more effective than L-NIL with IC₅₀ values of 9.37 μM. These findings not only enriched the types of anti-inflammatory compounds in N. incisum but also provided some useful information for predicting their oral bioavailability and their suitability as drug leads or promising anti-inflammatory agents. Full article

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Variability in the Content of Trans-Resveratrol, Trans-ε-Viniferin and R2-Viniferin in Grape Cane of Seven Vitis vinifera L. Varieties during a Three-Year Study

by Jan Tříska, Naděžda Vrchotová, Josef Balík, Ivo Soural and Radek Sotolář

Molecules 2017, 22(6), 928; https://doi.org/10.3390/molecules22060928 - 3 Jun 2017

Cited by 17 | Viewed by 4803

Abstract

Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South [...] Read more.

Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South Moravia, Czech Republic were extracted, and the contents of trans-resveratrol, trans-ε-viniferin, and r2-viniferin were determined by high-performance liquid chromatography. The study included three blue grape varieties of Vitis vinifera L. (Cabernet Moravia, Blaufränkisch, and Piwi variety Laurot) and four white grape varieties (Chardonnay, Green Veltliner, Piwi variety Hibernal, and Piwi variety Malverina). From the viewpoint of producing extracts with high stilbenes content, the Hibernal variety is clearly the best. The mean amounts of the stilbenes for this variety at all localities and for all three years were 4.99 g/kg for trans-resveratrol, 3.24 g/kg for trans-ε-viniferin, and 1.73 g/kg for r2-viniferin. The influence of vintage, locality, and variety on the amounts of stilbenes was studied using PCA analysis. In contrast to expectations, there was no strong impact of locality on stilbenes content. The differences were varietal for most varieties, regardless of the area of cultivation. Laurot and Hibernal varieties did differ significantly in that respect, however, as they exhibited clear dependence on location. Full article

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Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide

by Xiaoqiang Chen, Wei Song, Jin Zhao, Zhifa Zhang and Yuntian Zhang

Molecules 2017, 22(6), 914; https://doi.org/10.3390/molecules22060914 - 31 May 2017

Cited by 27 | Viewed by 5158

Abstract

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in [...] Read more.

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200–700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid–base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(−)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains. Full article

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Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A

by Suresh Kumar, Rajiv Dahiya, Sukhbir Lal Khokra, Rita Mourya, Suresh V. Chennupati and Sandeep Maharaj

Molecules 2017, 22(6), 682; https://doi.org/10.3390/molecules22060682 - 27 May 2017

Cited by 14 | Viewed by 5635

Abstract

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of [...] Read more.

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, ¹³C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines. Full article

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Identification of Anthocyanin Composition and Functional Analysis of an Anthocyanin Activator in Solanum nigrum Fruits

by Shaoli Wang, Zhaohui Chu, Mingxing Ren, Ru Jia, Changbao Zhao, Dan Fei, Hao Su, Xiaoqi Fan, Xiaotian Zhang, Yang Li, Yingzi Wang and Xinhua Ding

Molecules 2017, 22(6), 876; https://doi.org/10.3390/molecules22060876 - 25 May 2017

Cited by 29 | Viewed by 7570

Abstract

Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In [...] Read more.

Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In this study, we determined that the peel and flesh of S. nigrum fruits shared similar HPLC profiles but different contents and total antioxidant activities for anthocyanins. After an efficient purification method, mainly including extraction with pH 1.0 distilled water and then desorption with pH 1.0 95% ethanol after a DM-130 resin adsorption step to obtain more pure anthocyanin extracts, the purity of anthocyanins extracted from S. nigrum fruits reached 56.1%. Moreover, eight anthocyanins from S. nigrum fruit were identified with HPLC-MS/MS for the first time. A typical R2R3-MYB transcription factor gene, SnMYB, was also cloned for the first time by rapid amplification of cDNA ends (RACE)-PCR from S. nigrum. Moreover, the contents of anthocyanins were shown to correlate well (r = 0.93) with the expression levels of SnMYB gene during the fruit’s developmental stages. Most significantly, SnMYB gene successfully produced high anthocyanin content (1.03 mg/g) when SnMYB gene was transiently expressed in tobacco leaves. Taken together, S. nigrum fruits are a promising resource for anthocyanin extraction, and SnMYB gene is an activator that positively regulates anthocyanin biosynthesis in S. nigrum. Full article

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Open AccessArticle

Impact of Maturity of Malay Cherry (Lepisanthes alata) Leaves on the Inhibitory Activity of Starch Hydrolases

by Yan Zhang, Yuyang Gui and Dejian Huang

Molecules 2017, 22(6), 873; https://doi.org/10.3390/molecules22060873 - 24 May 2017

Cited by 2 | Viewed by 4360

Abstract

Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS² results showed that the active components in young leaves were proanthocyanidins with lower [...] Read more.

Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS² results showed that the active components in young leaves were proanthocyanidins with lower mean degrees of polymerisation (≤10). The IC₅₀ of the aqueous extracts of young leaves were 2.50 ± 0.03 and 12.91 ± 0.29 µg/mL, against α-amylase and α-glucosidase, which make them less active compared to the mature leaves. In contrast, total proanthocyanidins in aqueous extracts decreased as the leaves matured, indicating that the compounds in the mature leaves have much higher activity. However, there was no significant difference in the digestibility of wheat noodles incorporated with the aqueous extracts from either young or mature leaves. Interestingly, with regard to rice noodles, their digestibility was mostly reduced by incorporating aqueous extracts of young leaves compared to using mature leaves. Full article

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Open AccessArticle

New Glycosides from the Fruits of Nicandra physaloides

by Yan Liu, Hai-Bing Jiang, Zhen-Peng Xu, Yan-Gang Cheng, Shao-Wa Lv, Bing-You Yang, Hong-Wei Guo and Hai-Xue Kuang

Molecules 2017, 22(5), 828; https://doi.org/10.3390/molecules22050828 - 17 May 2017

Cited by 14 | Viewed by 5595

Abstract

Three new glycosides (1–3) and 15 known ones (4–18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. [...] Read more.

Three new glycosides (1–3) and 15 known ones (4–18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4–18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC₅₀ values from 26.9 to 47.5 μM. Full article

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Isolaurenidificin and Bromlaurenidificin, Two New C₁₅-Acetogenins from the Red Alga Laurencia obtusa

by Nahed O. Bawakid, Walied M. Alarif, Najla A. Alburae, Hajer S. Alorfi, Khalid O. Al-Footy, Sultan S. Al-Lihaibi and Mohamed A. Ghandourah

Molecules 2017, 22(5), 807; https://doi.org/10.3390/molecules22050807 - 15 May 2017

Cited by 12 | Viewed by 4946

Abstract

Chromatographic fractionation of the CH₂Cl₂/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C₁₅-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based [...] Read more.

Chromatographic fractionation of the CH₂Cl₂/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C₁₅-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based on extensive analyses of their spectral data. Compounds 1 and 2 showed no toxicity (LC₅₀ > 12 mM) using Artemia salina as test organism. Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and PC-3 cells, however, they exhibited a relatively potent cytotoxic activity against peripheral blood neutrophils. This can be attributed partly to induction of apoptosis. Full article

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Open AccessReview

Bioactive Natural Products of Marine Sponges from the Genus Hyrtios

by Nourhan Hisham Shady, Ebaa M. El-Hossary, Mostafa A. Fouad, Tobias A. M. Gulder, Mohamed Salah Kamel and Usama Ramadan Abdelmohsen

Molecules 2017, 22(5), 781; https://doi.org/10.3390/molecules22050781 - 11 May 2017

Cited by 41 | Viewed by 8923

Abstract

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios [...] Read more.

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable. Full article

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Ontogenetic Variation of Individual and Total Capsaicinoids in Malagueta Peppers (Capsicum frutescens) during Fruit Maturation

by Oreto Fayos, Ana Carolina De Aguiar, Ana Jiménez-Cantizano, Marta Ferreiro-González, Ana Garcés-Claver, Julián Martínez, Cristina Mallor, Ana Ruiz-Rodríguez, Miguel Palma, Carmelo G. Barroso and Gerardo F. Barbero

Molecules 2017, 22(5), 736; https://doi.org/10.3390/molecules22050736 - 3 May 2017

Cited by 25 | Viewed by 7613

Abstract

The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature [...] Read more.

The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature and humidity conditions. Capsaicinoids were extracted using ultrasound-assisted extraction (UAE) and the extracts were analyzed by ultra-performance liquid chromatography (UHPLC) with fluorescence detection. A significant increase in the total content of capsaicinoids was observed in the early days (between 12 and 33). Between day 33 and 40 there was a slight reduction in the total capsaicinoid content (3.3% decrease). C was the major capsaicinoid, followed by DHC, n-DHC, h-C and h-DHC. By considering the evolution of standardized values of the capsaicinoids it was verified that n-DHC, DHC and h-DHC (dihydrocapsaicin-like capsaicinoids) present a similar behavior pattern, while h-C and C (capsaicin-like capsaicinoids) show different evolution patterns. Full article

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Pectic Bee Pollen Polysaccharide from Rosa rugosa Alleviates Diet-Induced Hepatic Steatosis and Insulin Resistance via Induction of AMPK/mTOR-Mediated Autophagy

by Xinzhi Li, Haiquan Gong, Siwen Yang, Lulu Yang, Yuying Fan and Yifa Zhou

Molecules 2017, 22(5), 699; https://doi.org/10.3390/molecules22050699 - 28 Apr 2017

Cited by 68 | Viewed by 8055

Abstract

Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by ¹³C-NMR and Fourier transform-infrared [...] Read more.

Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by ¹³C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains. In vivo studies demonstrated that RBPP-P markedly ameliorated insulin resistance, glucose intolerance, and liver steatosis in obese mice. The suppressive effects of RBPP-P on liver steatosis and triglyceride content were mediated by increased autophagy and lipase expression in liver. In AMPK knockdown cells (prkaa 1/2^−/− MEF) and HFD-fed mice tissues (liver, gonadal white adipose, and inguinal white adipose), RBPP-P enhanced autophagy in AMPK/mTOR-dependent way in liver, but not in adipose tissue. These findings demonstrated that bee pollen polysaccharide alleviated liver steatosis and insulin resistance by promoting autophagy via an AMPK/mTOR-mediated signaling pathway, suggesting that RBPP-P could be a novel therapeutic agent used for the treatment of obesity and diabetes. Full article

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Modification of Natural Eudesmane Scaffolds via Mizoroki-Heck Reactions

by Mohamed Zaki, Mohamed Akssira and Sabine Berteina-Raboin

Molecules 2017, 22(4), 652; https://doi.org/10.3390/molecules22040652 - 20 Apr 2017

Viewed by 5161

Abstract

The Mizoroki-Heck reaction was applied to substrates derived from isocostic and ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter that were extracted directly from plant material collected in Morocco. After optimization of the metallo-catalysis conditions, various aryl-groups were successfully introduced on [...] Read more.

The Mizoroki-Heck reaction was applied to substrates derived from isocostic and ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter that were extracted directly from plant material collected in Morocco. After optimization of the metallo-catalysis conditions, various aryl-groups were successfully introduced on the exocyclic double bond with an exclusive E-configuration and without racemization. Full article

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Open AccessArticle

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

by Wioleta Pietrzak, Renata Nowak, Urszula Gawlik-Dziki, Marta Kinga Lemieszek and Wojciech Rzeski

Molecules 2017, 22(4), 624; https://doi.org/10.3390/molecules22040624 - 12 Apr 2017

Cited by 47 | Viewed by 6911

Abstract

A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic [...] Read more.

A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) as well as an antioxidant and antiproliferative activity were evaluated for the first time. The plant material was selectively extracted using ultrasound assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC results varied from 7.146 to 9.345 mg GA g⁻¹ and from 1.888 to 2.888 mg Q g⁻¹ of dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest content of phenolic acids in mistletoe berries from Populus nigra ‘Italica’ L. and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 µg and 5.955 µg per g dry extract, respectively). The moderate antioxidant activity of investigated extracts was obtained. The studies revealed that the examined extracts decreased the proliferation of human colon adenocarcinoma cells line LS180 in a dose-dependent manner without cytotoxicity in the human colon epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest considerable impact of polyphenols on the anticancer activity of these extracts. Full article

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Essential Oils of Hyptis pectinata Chemotypes: Isolation, Binary Mixtures and Acute Toxicity on Leaf-Cutting Ants

by Rosana B. Feitosa-Alcantara, Leandro Bacci, Arie F. Blank, Péricles B. Alves, Indira Morgana de A. Silva, Caroline A. Soares, Taís S. Sampaio, Paulo Cesar de L. Nogueira and Maria De Fátima Arrigoni-Blank

Molecules 2017, 22(4), 621; https://doi.org/10.3390/molecules22040621 - 12 Apr 2017

Cited by 20 | Viewed by 6179

Abstract

Leaf-cutting ants are pests of great economic importance due to the damage they cause to agricultural and forest crops. The use of organosynthetic insecticides is the main form of control of these insects. In order to develop safer technology, the objective of this [...] Read more.

Leaf-cutting ants are pests of great economic importance due to the damage they cause to agricultural and forest crops. The use of organosynthetic insecticides is the main form of control of these insects. In order to develop safer technology, the objective of this work was to evaluate the formicidal activity of the essential oils of two Hyptis pectinata genotypes (chemotypes) and their major compounds on the leaf-cutting ants Acromyrmex balzani Emery and Atta sexdens rubropilosa Forel. Bioassays of exposure pathways (contact and fumigation) and binary mixtures of the major compounds were performed. The major compounds identified in the essential oils of H. pectinata were β-caryophyllene, caryophyllene oxide and calamusenone. The essential oils of H. pectinata were toxic to the ants in both exposure pathways. Essential oils were more toxic than their major compounds alone. The chemotype calamusenone was more toxic to A. balzani in both exposure pathways. A. sexdens rubropilosa was more susceptible to the essential oil of the chemotype β-caryophyllene in both exposure pathways. In general, the binary mixtures of the major compounds resulted in additive effect of toxicity. The essential oils of H. pectinata is a raw material of great potential for the development of new insecticides. Full article

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Open AccessArticle

Phenolic Compounds from the Rhizomes of Smilax china L. and Their Anti-Inflammatory Activity

by Cheng Zhong, Deng Hu, Lian-Bing Hou, Lu-Yao Song, Ying-Jun Zhang, Yang Xie and Li-Wen Tian

Molecules 2017, 22(4), 515; https://doi.org/10.3390/molecules22040515 - 3 Apr 2017

Cited by 22 | Viewed by 6568

Abstract

A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (2–7), nine flavonoids (8–16), two stilbenoids (17, 18), [...] Read more.

A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (2–7), nine flavonoids (8–16), two stilbenoids (17, 18), and two other compounds (19, 20). The structure of compound 1 was determined on the basis of 1D, 2D NMR and HR-ESI-MS data, as well as chemical method. Compounds 2–5, 8–12, 15, 17, and 19 were evaluated for anti-inflammatory activity. Only compounds 10, 15 and 17 showed slightly IL-1β expression inhibitory activities on LPS induced THP-1 cells, with inhibition rate of 15.8%, 37.3%, and 35.8%, respectively, at concentration of 50 μg/mL. Full article

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Intestinal Transport Characteristics and Metabolism of C-Glucosyl Dihydrochalcone, Aspalathin

by Sandra Bowles, Elizabeth Joubert, Dalene De Beer, Johan Louw, Christel Brunschwig, Mathew Njoroge, Nina Lawrence, Lubbe Wiesner, Kelly Chibale and Christo Muller

Molecules 2017, 22(4), 554; https://doi.org/10.3390/molecules22040554 - 30 Mar 2017

Cited by 12 | Viewed by 6255

Abstract

Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability [...] Read more.

Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability (P_app) typical of poorly absorbed compounds (1.73 × 10⁻⁶ cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10⁻⁶ cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the P_app of aspalathin was not affected by the presence of specific inhibitors. The P_app of aspalathin was also not affected by constituents of aspalathin-enriched rooibos extracts, but was affected by high glucose concentration (20.5 mM), which decreased the P_app value to 2.9 × 10⁻⁷ cm/s. Aspalathin metabolites (sulphated, glucuronidated and methylated) were found in mouse urine, but not in blood, following an oral dose of 50 mg/kg body weight of the pure compound. Sulphates were the predominant metabolites. These findings suggest that aspalathin is absorbed and metabolised in mice to mostly sulphate conjugates detected in urine. Mechanistically, we showed that aspalathin is not actively transported by the glucose transporters, but presumably passes the monolayer paracellularly. Full article

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Assessment of Lipophilicity Indices Derived from Retention Behavior of Antioxidant Compounds in RP-HPLC

by Ioana Anamaria Sima, Agata Kot-Wasik, Andrzej Wasik, Jacek Namieśnik and Costel Sârbu

Molecules 2017, 22(4), 550; https://doi.org/10.3390/molecules22040550 - 29 Mar 2017

Cited by 21 | Viewed by 5670

Abstract

Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different [...] Read more.

Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different HPLC columns: RP18 (LiChroCART, Purosphere RP-18e), C8 (Zorbax, Eclipse XDBC8), C16-Amide (Discovery RP-Amide C16), CN100 (Saulentechnik, Lichrosphere), and pentafluorophenyl (Phenomenex, Kinetex PFP), and the mobile phase consisted of methanol and water (0.1% formic acid) in different proportions. The measurements were conducted at two different column temperatures, room temperature (22 °C) and, in order to mimic the environment from the human body, 37 °C. Furthermore, principal component analysis (PCA) was used to obtain new lipophilicity indices and holistic lipophilicity charts. Additionally, highly representative depictions of the chromatographic behavior of the investigated compounds and stationary phases at different temperatures were obtained using two new chemometric approaches, namely two-way joining cluster analysis and sum of ranking differences. Full article

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Open AccessArticle

Rapid Determination of 30 Polyphenols in Tongmai Formula, a Combination of Puerariae Lobatae Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Chuanxiong Rhizoma, via Liquid Chromatography-Tandem Mass Spectrometry

by Fu-Rong Wang, Ying Zhang, Xin-Bao Yang, Chun-Xu Liu, Xiu-Wei Yang, Wei Xu and Jian-Xun Liu

Molecules 2017, 22(4), 545; https://doi.org/10.3390/molecules22040545 - 29 Mar 2017

Cited by 12 | Viewed by 7593

Abstract

Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and [...] Read more.

Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and convenient analytical method for a comprehensive determination of polyphenols in TMF and the ascertainment of their chemical correlations with its herbal components, a method combining high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for rapid determination of 30 polyphenols in TMF and its three herbal components. The chromatographic separation was carried out on a Chromolith Fastgradient RP-18 endcapped 50-2 column using an optimized gradient elution. Statistical analysis of obtained data demonstrated that the method had a desirable linearity, precision, and accuracy, as well as excellent sensitivity. The obtained results indicated that, among the 30 polyphenols in TMF, 22 originated from Gegen, 6 originated from Danshen, and 2 originated from Chuanxiong. The major polyphenols in TMF have been identified as puerarin, mirificin, salvianolic acid B, salvianic acid A, 3’-hydroxypuerarin, 3’-methoxypuerarin, and salvianolic acid A, with a combined contribution of 19.2% of the preparation. The development and validation of this method will greatly facilitate future pharmacological studies of TMF and its herbal components, as well as polyphenols in cardiovascular therapies. Full article

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Open AccessArticle

3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways

by Wei Chao, Jeng-Shyan Deng, Pei-Ying Li, Yu-Chia Liang and Guan-Jhong Huang

Molecules 2017, 22(4), 537; https://doi.org/10.3390/molecules22040537 - 28 Mar 2017

Cited by 43 | Viewed by 6533

Abstract

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited [...] Read more.

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways. Full article

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Open AccessArticle

Anti-Melanogenic Properties of Greek Plants. A Novel Depigmenting Agent from Morus alba Wood

by Eliza Chaita, George Lambrinidis, Christina Cheimonidi, Adamantia Agalou, Dimitris Beis, Ioannis Trougakos, Emmanuel Mikros, Alexios-Leandros Skaltsounis and Nektarios Aligiannis

Molecules 2017, 22(4), 514; https://doi.org/10.3390/molecules22040514 - 23 Mar 2017

Cited by 66 | Viewed by 7571

Abstract

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, [...] Read more.

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells. Bioassay-guided isolation led to the acquisition of twelve compounds: oxyresveratrol (1), kuwanon C (2), mulberroside A (3), resorcinol (4), dihydrooxyresveratol (5), trans-dihydromorin (6), 2,4,3′-trihydroxydihydrostilbene (7), kuwanon H (8), 2,4-dihydroxybenzaldehyde (9), morusin (10), moracin M (11) and kuwanon G (12). Among these, 2,4,3′-trihydroxydihydrostilbene (7) is isolated for the first time from Morus alba and constitutes a novel potent tyrosinase inhibitor (IC50 0.8 ± 0.15). We report here for the first time dihydrooxyresveratrol (5) as a potent natural tyrosinase inhibitor (IC50 0.3 ± 0.05). Computational docking analysis indicated the binding modes of six tyrosinase inhibitors with the aminoacids of the active centre of tyrosinase. Finally, we found both MAM extract and compounds 1, 6 and 7 to significantly suppress in vivo melanogenesis during zebrafish embryogenesis. Full article

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Open AccessReview

Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells

by Alessandra Bosco and Roy M. Golsteyn

Molecules 2017, 22(3), 459; https://doi.org/10.3390/molecules22030459 - 13 Mar 2017

Cited by 28 | Viewed by 8439

Abstract

We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain [...] Read more.

We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain types of sesquiterpenes can arrest cells in mitosis as measured by cell biology, biochemical and imaging techniques. We have listed the sesquiterpenes that arrest cells in mitosis and analyzed the biological data that support those observations. In view of the biochemical complexity of mitosis, we propose that a subset of sesquiterpenes have a unique chemical structure that can target a precise protein(s) required for mitosis. Since the process of mitotic arrest precedes that of cell death, it is possible that some sesquiterpenes that are currently classified as cytotoxic might also induce a mitotic arrest. Our analysis provides a new perspective of sesquiterpene chemical biology Full article

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Open AccessReview

Pentacyclic Triterpene Bioavailability: An Overview of In Vitro and In Vivo Studies

by Niege A. J. C. Furtado, Laetitia Pirson, Hélène Edelberg, Lisa M. Miranda, Cristina Loira-Pastoriza, Véronique Preat, Yvan Larondelle and Christelle M. André

Molecules 2017, 22(3), 400; https://doi.org/10.3390/molecules22030400 - 4 Mar 2017

Cited by 155 | Viewed by 11285

Abstract

Pentacyclic triterpenes are naturally found in a great variety of fruits, vegetables and medicinal plants and are therefore part of the human diet. The beneficial health effects of edible and medicinal plants have partly been associated with their triterpene content, but the in [...] Read more.

Pentacyclic triterpenes are naturally found in a great variety of fruits, vegetables and medicinal plants and are therefore part of the human diet. The beneficial health effects of edible and medicinal plants have partly been associated with their triterpene content, but the in vivo efficacy in humans depends on many factors, including absorption and metabolism. This review presents an overview of in vitro and in vivo studies that were carried out to determine the bioavailability of pentacyclic triterpenes and highlights the efforts that have been performed to improve the dissolution properties and absorption of these compounds. As plant matrices play a critical role in triterpene bioaccessibility, this review covers literature data on the bioavailability of pentacyclic triterpenes ingested either from foods and medicinal plants or in their free form. Full article

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Open AccessArticle

New Cytotoxic Seco-Type Triterpene and Labdane-Type Diterpenes from Nuxia oppositifolia

by Shaza M. Al-Massarani, Ali A. El-Gamal, Mohammad K. Parvez, Mohammed S. Al-Dosari, Mansour S. Al-Said, Maged S. Abdel-Kader and Omer A. Basudan

Molecules 2017, 22(3), 389; https://doi.org/10.3390/molecules22030389 - 2 Mar 2017

Cited by 6 | Viewed by 5709

Abstract

Chromatographic purification of the n-hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid (1), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (2), 2β-acetoxy-6-oxolabda-7-en-15-oic acid ( [...] Read more.

Chromatographic purification of the n-hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid (1), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (2), 2β-acetoxy-6-oxolabda-7-en-15-oic acid (3), and one new seco-triterpene, 3,4-seco olean-12-en-3,30 dioic acid (4), together with 10 known lupane, oleanane and ursane-type triterpenes, as well as the common phytosterols, β-sitosterol and stigmasterol (5–16). Their structures have been assigned on the basis of different spectroscopic techniques including 1D and 2D NMR. Moreover, 13 of the isolated compounds were tested on the human cancer cell lines HeLa (cervical), A549 (lung) and MDA (breast), and most of the compounds showed potent cytotoxic activities in vitro. Full article

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Open AccessArticle

Is Gamma Radiation Suitable to Preserve Phenolic Compounds and to Decontaminate Mycotoxins in Aromatic Plants? A Case-Study with Aloysia citrodora Paláu

by Eliana Pereira, Lillian Barros, Amilcar L. Antonio, Sandra Cabo Verde, Celestino Santos-Buelga, Isabel C. F. R. Ferreira and Paula Rodrigues

Molecules 2017, 22(3), 347; https://doi.org/10.3390/molecules22030347 - 23 Feb 2017

Cited by 30 | Viewed by 6711

Abstract

This study aimed to determine the effect of gamma radiation on the preservation of phenolic compounds and on decontamination of dry herbs in terms of ochratoxin A (OTA) and aflatoxin B1 (AFB1), using Aloysia citrodora Paláu as a case study. For this purpose, [...] Read more.

This study aimed to determine the effect of gamma radiation on the preservation of phenolic compounds and on decontamination of dry herbs in terms of ochratoxin A (OTA) and aflatoxin B1 (AFB1), using Aloysia citrodora Paláu as a case study. For this purpose, artificially contaminated dry leaves were submitted to gamma radiation at different doses (1, 5, and 10 kGy; at dose rate of 1.7 kGy/h). Phenolic compounds were analysed by HPLC-DAD-ESI/MS and mycotoxin levels were determined by HPLC-fluorescence. Eleven phenolic compounds were identified in the samples and despite the apparent degradation of some compounds (namely verbasoside), 1 and 10 kGy doses point to a preservation of the majority of the compounds. The mean mycotoxin reduction varied between 5.3% and 9.6% for OTA and from 4.9% to 5.2% for AFB1. It was not observed a significant effect of the irradiation treatments on mycotoxin levels, and a slight degradation of the phenolic compounds in the irradiated samples was observed. Full article

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Open AccessArticle

Simultaneous Quantification of Nine New Furanocoumarins in Angelicae Dahuricae Radix Using Ultra-Fast Liquid Chromatography with Tandem Mass Spectrometry

by Lei Zhang, Wei Wei and Xiu-Wei Yang

Molecules 2017, 22(2), 322; https://doi.org/10.3390/molecules22020322 - 20 Feb 2017

Cited by 12 | Viewed by 5519

Abstract

A series of new furanocoumarins with long-chain hydrophobic groups, namely andafocoumarins A–H and J, have been isolated from the dried roots of Angelica dahurica cv. Hangbaizhi (Angelicae Dahuricae radix) in our previous study, among which andafocoumarins A and B were demonstrated to have [...] Read more.

A series of new furanocoumarins with long-chain hydrophobic groups, namely andafocoumarins A–H and J, have been isolated from the dried roots of Angelica dahurica cv. Hangbaizhi (Angelicae Dahuricae radix) in our previous study, among which andafocoumarins A and B were demonstrated to have better anti-inflammatory activity than the positive controls. In this work, a sensitive, accurate, and efficient ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometer (UFLC-MS/MS) method was developed and validated for simultaneous quantification of above-mentioned nine compounds in four cultivars of Angelicae Dahuricae Radix. Chromatographic separation was performed on a Kinetex 2.6u C18 100 Å column (100 × 2.1 mm, 2.6 µm). The mobile phases were comprised of acetonitrile and water with a flow rate of 0.5 mL/min. Using the established method, all components could be easily separated within 12 min. With the multiple reaction monitor mode, all components were detected in positive electrospray ionization. The method was validated with injection precision, linearity, lower limit of detection, lower limit of quantification, precision, recovery, and stability, respectively. The final results demonstrated that the method was accurate and efficient, which could be used to simultaneously quantify the nine andafocoumarins in Angelicae Dahuricae Radix. The results also indicated that in different batches of Angelicae Dahuricae Radix, some of the andafocoumarins were significantly different in terms of content. Full article

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Open AccessArticle

Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia

by Sonia Escandón-Rivera, Araceli Pérez-Vásquez, Andrés Navarrete, Mariana Hernández, Edelmira Linares, Robert Bye and Rachel Mata

Molecules 2017, 22(2), 289; https://doi.org/10.3390/molecules22020289 - 14 Feb 2017

Cited by 16 | Viewed by 7337

Abstract

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and [...] Read more.

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4′,7-dimethylapigenin (8). In addition, the structure of calein C (5) was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6–316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene 1 was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes 1 and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2) was developed and validated according to standard protocols. Full article

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Open AccessReview

Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review

by Oludemi Taofiq, Ana M. González-Paramás, Maria Filomena Barreiro and Isabel C. F. R. Ferreira

Molecules 2017, 22(2), 281; https://doi.org/10.3390/molecules22020281 - 13 Feb 2017

Cited by 272 | Viewed by 16734

Abstract

Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, [...] Read more.

Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, as well as the limitations associated with their use in cosmetic formulations. Hydroxycinnamic acids and their derivatives display antioxidant, anti-collagenase, anti-inflammatory, antimicrobial and anti-tyrosinase activities, as well as ultraviolet (UV) protective effects, suggesting that they can be exploited as anti-aging and anti-inflammatory agents, preservatives and hyperpigmentation-correcting ingredients. Due to their poor stability, easy degradation and oxidation, microencapsulation techniques have been employed for topical application, preventing them from degradation and enabling a sustained release. Based on the above findings, hydroxycinnamic acids present high cosmetic potential, but studies addressing the validation of their benefits in cosmetic formulations are still scarce. Furthermore, studies dealing with skin permeation are scarcely available and need to be conducted in order to predict the topical bioavailability of these compounds after application. Full article

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Open AccessArticle

Bioactive Benzofuran Derivatives from Cortex Mori Radicis, and Their Neuroprotective and Analgesic Activities Mediated by mGluR₁

by Ya-Nan Wang, Mao-Feng Liu, Wei-Zhen Hou, Rui-Ming Xu, Jie Gao, An-Qi Lu, Mei-Ping Xie, Lan Li, Jian-Jun Zhang, Ying Peng, Li-Li Ma, Xiao-Liang Wang, Jian-Gong Shi and Su-Juan Wang

Molecules 2017, 22(2), 236; https://doi.org/10.3390/molecules22020236 - 8 Feb 2017

Cited by 34 | Viewed by 6825

Abstract

Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1 [...] Read more.

Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1), (9R)-moracin P 9-O-β-d-glucopyranoside (2), (9R)-moracin P 3′-O-β-d-glucopyranoside (3), and (9R)-moracin O 10-O-β-d-glucopyranoside (4) based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5), R (7), and P (8) showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5) and P (8) also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR₁) results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR₁ pathway. Full article

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Open AccessArticle

Flavonoid Composition and Antitumor Activity of Bee Bread Collected in Northeast Portugal

by Filipa Sobral, Ricardo C. Calhelha, Lillian Barros, Montserrat Dueñas, Andreia Tomás, Celestino Santos-Buelga, Miguel Vilas-Boas and Isabel C. F. R. Ferreira

Molecules 2017, 22(2), 248; https://doi.org/10.3390/molecules22020248 - 7 Feb 2017

Cited by 96 | Viewed by 11803

Abstract

Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives [...] Read more.

Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives located in different apiaries near Bragança, in the northeast region of Portugal, and one BB commercial sample were characterized by high-performance liquid chromatography coupled to a diode array detector and electrospray mass spectrometry (HPLC-DAD-ESI/MS) in terms of phenolic compounds, such as flavonoid glycoside derivatives. Furthermore, the samples were screened, using in vitro assays, against different human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HeLa (cervical carcinoma) and HepG2 (hepatocellular carcinoma), and also against non-tumor liver cells (porcine liver cells, PLP2). The main phenolic compounds found were flavonol derivatives, mainly quercetin, kaempferol, myricetin, isorhamnetin and herbacetrin glycoside derivatives. Thirty-two compounds were identified in the six BB samples, presenting BB1 and BB3 with the highest contents (6802 and 6480 µg/g extract, respectively) and the highest number of identified compounds. Two isorhamnetin glycoside derivatives, isrohamnetin-O-hexosyl-O-rutinoside and isorhamnetin-O-pentosyl-hexoside, were the most abundant compounds present in BB1; on the other hand, quercetin-3-O-rhamnoside was the most abundant flavonol in BB3. However, it was not possible to establish a correlation between the flavonoids and the observed low to moderate cytotoxicity (ranging from >400 to 68 µg/mL), in which HeLa and NCI-H460 cell lines were the most susceptible to the inhibition. To the authors’ knowledge, this is the first report characterizing glycosidic flavonoids in BB samples, contributing to the chemical knowledge of this less explored bee product. Full article

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Open AccessArticle

Identification of Larvicidal Constituents of the Essential Oil of Echinops grijsii Roots against the Three Species of Mosquitoes

by Mei Ping Zhao, Qi Zhi Liu, Qiyong Liu and Zhi Long Liu

Molecules 2017, 22(2), 205; https://doi.org/10.3390/molecules22020205 - 27 Jan 2017

Cited by 18 | Viewed by 6189

Abstract

The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography‐mass spectrometry (GC‐MS) analysis. [...] Read more.

The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography‐mass spectrometry (GC‐MS) analysis. GC‐MS analyses revealed the presence of 31 components, with 5‐(3‐buten‐1‐yn‐1‐yl)‐2,2′‐bithiophene (5‐BBT, 27.63%), αterthienyl (α‐T, 14.95%),1,8‐cineole (5.56%) and cis‐β‐ocimene (5.01%) being the four major constituents. Based bioactivity‐directed chromatographic separation of the essential oil led to the isolation of 5‐BBT, 5‐(4‐isovaleroyloxybut‐1‐ynyl)‐2,2′‐bithiophene (5‐IBT) and αT as active compounds. The essential oil of E. grijsii exhibited larvicidal activity against the fourth instar larvae of Aedes albopictus, Anopheles sinensis and Culex pipiens pallens with LC50 values of 2.65 μg/mL, 3.43 μg/mL and 1.47 μg/mL, respectively. The isolated thiophenes, 5‐BBT and 5‐IBT, possessed strong larvicidal activity against the fourth instar larvae of Ae. albopictus(LC50 = 0.34 μg/mL and 0.45 μg/mL, respectively) and An. sinensis(LC50 = 1.36 μg/mL and 5.36 μg/mL, respectively). The two isolated thiophenes also had LC50 values against the fourth instar larvae of C. pipiens pallens of 0.12 μg/mL and 0.33 μg/mL, respectively. The findings indicated that the essential oil of E. grijsii roots and the isolated thiophenes have an excellent potential for use in the control of Ae.albopictus, An. sinensis and C. pipiens pallens larvae and could be used in the search for new, safer and more effective natural compounds as larvicides. Full article

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Open AccessArticle

Chemical Characterization and Antioxidant Potential of Wild Ganoderma Species from Ghana

by Mary Obodai, Deborah L. Narh Mensah, Ângela Fernandes, Nii Korley Kortei, Matilda Dzomeku, Matthew Teegarden, Steven J. Schwartz, Lillian Barros, Juanita Prempeh, Richard K. Takli and Isabel C. F. R. Ferreira

Molecules 2017, 22(2), 196; https://doi.org/10.3390/molecules22020196 - 25 Jan 2017

Cited by 52 | Viewed by 7391

Abstract

The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1–LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty [...] Read more.

The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1–LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty acids, phenolic and other organic compounds and some vitamins and vitamin precursors. Antioxidant potential was evaluated by investigating reducing power, radical scavenging activity and lipid peroxidation inhibition using five in vitro assays. Protein, carbohydrate, fat, ash and energy contents ranged between 15.7–24.5 g/100 g·dw, 73.31–81.90 g/100 g, 0.48–1.40 g/100 g, 0.68–2.12 g/100 g ash and 396.1–402.02 kcal/100 g, respectively. Fatty acids such as linoleic, oleic and palmitic acids were relatively abundant. Free sugars included rhamnose, fructose, mannitol, sucrose and trehalose. Total tocopherols, organic acids and phenolic compounds’ content ranged between 741–3191 µg/100 g, 77–1003 mg/100 g and 7.6–489 µg/100 g, respectively. There were variations in the β-glucans, ergosterol and vitamin D₂ contents. The three major minerals in decreasing order were K > P > S. Ganoderma sp. strain AM1 showed the highest antioxidant activity. This study reveals, for the first time, chemical characteristics of Ganoderma spp. which grew simultaneously on the same tree. Full article

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Open AccessArticle

Polish Yellow Sweet Clover (Melilotus officinalis L.) Honey, Chromatographic Fingerprints, and Chemical Markers

by Izabela Jasicka-Misiak, Ewa Makowicz and Natalia Stanek

Molecules 2017, 22(1), 138; https://doi.org/10.3390/molecules22010138 - 15 Jan 2017

Cited by 30 | Viewed by 7798

Abstract

A case study of Polish Melilotus officinalis honey was presented for the first time. Gas chromatography–mass spectrometry (GC-MS) (after steam distillation, Soxhlet extraction, ultrasonic solvent extraction, and solid phase extraction (SPE)) and targeted high performance liquid chromatography with a photodiode array detector (HPLC-PAD) [...] Read more.

A case study of Polish Melilotus officinalis honey was presented for the first time. Gas chromatography–mass spectrometry (GC-MS) (after steam distillation, Soxhlet extraction, ultrasonic solvent extraction, and solid phase extraction (SPE)) and targeted high performance liquid chromatography with a photodiode array detector (HPLC-PAD) were applied to determine the characteristic components of honey. While ubiquitous in most honeys, carbohydrates, terpene derivatives, and phenylacetic acid dominated in the Soxhlet extracts (25.54%) and in the application of SPE (13.04%). In addition, lumichrome (1.85%) was found, and may be considered as a marker of this honey. Due to the presence of these compounds, Polish yellow sweet clover honey is similar to French lavender honeys. The major compounds determined in the methanolic extract were (+)-catechine (39.7%) and gallic acid (up to 30%), which can be regarded as specific chemical markers of the botanical origin of melilot honey. With respect to total phenolic and flavonoid contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were determined spectrophotometrically. The honey exhibited a moderate antioxidant activity, typical for light honeys, which correlates well with its phenolic and flavonoid composition. Full article

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Open AccessArticle

Anti-HBV Activities of Three Compounds Extracted and Purified from Herpetospermum Seeds

by Pu-Yang Gong, Zhi-Xiang Yuan, Jian Gu, Rui Tan, Jia-Chuan Li, Yan Ren and Sha Hu

Molecules 2017, 22(1), 14; https://doi.org/10.3390/molecules22010014 - 27 Dec 2016

Cited by 13 | Viewed by 6672

Abstract

The goal of this research was to evaluate the anti-hepatitis B virus (HBV) activities of three compounds extracted and purified from Herpetospermum seeds (HS) on HepG2.2.15 cells. Herpetin (HPT), herpetone (HPO), and herpetfluorenone (HPF) were isolated from HS and identified using HR-ESI-MS and [...] Read more.

The goal of this research was to evaluate the anti-hepatitis B virus (HBV) activities of three compounds extracted and purified from Herpetospermum seeds (HS) on HepG2.2.15 cells. Herpetin (HPT), herpetone (HPO), and herpetfluorenone (HPF) were isolated from HS and identified using HR-ESI-MS and NMR. Different concentrations of the drugs were added to the HepG2.2.15 cells. Cell toxicity was observed with an MTT assay, cell culture supernatants were collected, and HBsAg and HBeAg were detected by ELISA. The content of HBV DNA was determined via quantitative polymerase chain reaction (PCR) with fluorescent probes. The 50% toxicity concentration (TC₅₀) of HPF was 531.48 μg/mL, suggesting that this species is less toxic than HPT and HPO. HPT and HPF showed more potent antiviral activities than HPO. The 50% inhibition concentration (IC₅₀) values of HPF on HBsAg and HBeAg were 176.99 and 134.53 μg/mL, respectively, and the corresponding therapeutic index (TI) values were 2.66 and 3.49, respectively. HPT and HPF were shown to significantly reduce the level of HBV DNA in the HepG2.2.15 culture medium compared to the negative control. This initial investigation of the anti-HBV constituents of HS yielded three compounds that revealed a synergistic effect of multiple components in the ethnopharmacological use of HS. Full article

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Open AccessArticle

Simultaneous Determination of Multiple Components in Guanjiekang in Rat Plasma via the UPLC–MS/MS Method and Its Application in Pharmacokinetic Study

by Jian Wu, Ying Xie, Zheng Xiang, Canjian Wang, Hua Zhou and Liang Liu

Molecules 2016, 21(12), 1732; https://doi.org/10.3390/molecules21121732 - 16 Dec 2016

Cited by 12 | Viewed by 5899

Abstract

Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of [...] Read more.

Guanjiekang (GJK) that is formed by five medicinal herbs including Astragali Radix, Aconiti Lateralis Radix Praeparaia, Glycyrrhizae Radix et Rhizoma, Corydalis Rhizoma and Paeoniae Radix Alba was used for the treatment of rheumatoid arthritis (RA). However, the pharmacokinetic (PK) profile of active components in GJK remains unclear. This study aims to evaluate the pharmacokinetic behavior of seven representative active constituents in GJK (i.e., benzoylhypaconine, benzoylmesaconine, paeoniflorin, tetrahydropalmatine, calycosin-7-glucoside, formononetin and isoliquiritigenin) after oral administration of GJK in rats. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometer (UPLC–MS/MS) method has been successfully developed for the simultaneous determination of these seven constituents in rat plasma. Chromatographic separation was achieved on a C₁₈ column with a gradient elution program that consists of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.35 mL/min. Detection was performed under the multiple reaction monitoring (MRM) in the positive electrospray ionization (ESI) mode. The calibration curves exhibited good linearity (R² > 0.99) over a wide concentration range for all constituents. The accuracies ranged from 92.9% to 107.8%, and the intra-day and inter-day precisions at three different levels were below 15%. Our PK results showed that these seven compounds were quickly absorbed after the administration of the GJK product, and T_max ranged from 30 min to 189 min. The in vivo concentrations of paeoniflorin and isoliquiritigenin were significantly higher than the reported in vitro effective doses, indicating that they could partly contribute to the therapeutic effect of GJK. Therefore, we conclude that pharmacokinetic studies of representative bioactive chemicals after administration of complex herbal products are not only necessary but also feasible. Moreover, these seven compounds that were absorbed in vivo can be used as indicator standards for quality control and for determining pharmacokinetic behavior of herbal medicines in clinical studies. Full article

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Open AccessArticle

Impact of Cluster Zone Leaf Removal on Grapes cv. Regent Polyphenol Content by the UPLC-PDA/MS Method

by Kamila Mijowska, Ireneusz Ochmian and Jan Oszmiański

Molecules 2016, 21(12), 1688; https://doi.org/10.3390/molecules21121688 - 11 Dec 2016

Cited by 26 | Viewed by 5867

Abstract

Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal [...] Read more.

Abstract: Leaf removal is known to enhance light exposure of clusters and therefore may affect grape composition. Owing to the risk of decreasing grape quality or sunburn as a consequence of improper sun exposure, it is crucial to determine the optimum leaf removal techniques adequate for the particular climate conditions of a vineyard area. Defoliation experiments on vine cv. Regent were conducted in two consecutive years (2014 and 2015). The effect of leaf removal treatment on the qualitative and quantitative composition of the polyphenol compounds in the grapes, with reference to the basic weather conditions of the vineyard area, located in Szczecin in the North-Western part of Poland, was assessed. Defoliation was performed manually in the cluster zone at three phenological plant stages: pre-flowering, berry-set and véraison. Leaf removal, especially early defoliation (pre-flowering), enhanced total polyphenol content, including the amount of anthocyanins, flavonols and flavan-3-ols and furthermore, it increased the amount of soluble solids, decreasing the titratable acidity in grapes. On the other hand, the treatments had a reducing impact on the phenolic acids in berries. Defoliation at earlier stages of cluster development appears to be an efficient strategy for improving berry quality in cool climate areas, however, additionally further weather data control is required to determine the effects on berry components. Full article

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Open AccessArticle

Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury

by Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian and Ji-Xing Nan

Molecules 2016, 21(11), 1490; https://doi.org/10.3390/molecules21111490 - 9 Nov 2016

Cited by 47 | Viewed by 8281

Abstract

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like [...] Read more.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury. Full article

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Isobutylhydroxyamides from Zanthoxylum bungeanum and Their Suppression of NO Production

by Yuan Wang, Chun-Huan Li, Bo Luo, Ya Nan Sun, Young Ho Kim, An-Zhi Wei and Jin-Ming Gao

Molecules 2016, 21(10), 1416; https://doi.org/10.3390/molecules21101416 - 23 Oct 2016

Cited by 36 | Viewed by 6474

Abstract

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E [...] Read more.

Four new unsaturated aliphatic acid amides, named zanthoamides A–D (1–4), and eight known ones—tetrahydrobungeanool (5), ZP-amide A (6), ZP-amide B (7), ZP-amide C (8), ZP-amide D (9), ZP-amide E (10), bugeanumamide A (11), and (2E,7E,9E)-N-(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide (12)—were isolated from the pericarps of Zanthoxylum bungeanum. The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound 4 contained a rare C₆ fatty acid unit with an acetal group. Results revealed that compounds 1, 5, 6, and 12 showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with IC₅₀values of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC₅₀ > 60 μM). They could contribute to the anti-inflammatory effects of Z. bungeanum by suppression of NO production. Full article

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Open AccessArticle

Development of Mushroom-Based Cosmeceutical Formulations with Anti-Inflammatory, Anti-Tyrosinase, Antioxidant, and Antibacterial Properties

by Oludemi Taofiq, Sandrina A. Heleno, Ricardo C. Calhelha, Maria José Alves, Lillian Barros, Maria Filomena Barreiro, Ana M. González-Paramás and Isabel C. F. R. Ferreira

Molecules 2016, 21(10), 1372; https://doi.org/10.3390/molecules21101372 - 14 Oct 2016

Cited by 78 | Viewed by 11437

Abstract

The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow [...] Read more.

The cosmetic industry is in a constant search for natural compounds or extracts with relevant bioactive properties, which became valuable ingredients to design cosmeceutical formulations. Mushrooms have been markedly studied in terms of nutritional value and medicinal properties. However, there is still slow progress in the biotechnological application of mushroom extracts in cosmetic formulations, either as antioxidants, anti-aging, antimicrobial, and anti-inflammatory agents or as hyperpigmentation correctors. In the present work, the cosmeceutical potential of ethanolic extracts prepared from Agaricus bisporus, Pleurotus ostreatus, and Lentinula edodes was analyzed in terms of anti-inflammatory, anti-tyrosinase, antioxidant, and antibacterial activities. The extracts were characterized in terms of phenolic acids and ergosterol composition, and further incorporated in a base cosmetic cream to achieve the same bioactive purposes. From the results obtained, the final cosmeceutical formulations presented 85%–100% of the phenolic acids and ergosterol levels found in the mushroom extracts, suggesting that there was no significant loss of bioactive compounds. The final cosmeceutical formulation also displayed all the ascribed bioactivities and as such, mushrooms can further be exploited as natural cosmeceutical ingredients. Full article

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Chemical Compositions of Ligusticum chuanxiong Oil and Lemongrass Oil and Their Joint Action against Aphis citricola Van Der Goot (Hemiptera: Aphididae)

by Chao Zhang, Runqiang Liu, Jun He, Zhiqing Ma and Xing Zhang

Molecules 2016, 21(10), 1359; https://doi.org/10.3390/molecules21101359 - 12 Oct 2016

Cited by 19 | Viewed by 7625

Abstract

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass [...] Read more.

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography–mass spectrometry (GC-MS) analysis revealed that the main compounds from LCO were (Z)-ligustilide (44.58%) and senkyunolide A (26.92%), and that of LO were geranial (42.16%) and neral (32.58%), respectively. The mixture of LCO and LO showed significant synergy against A. citricola, with a common-toxicity coefficient (CTC) value of 221.46 at the optimal ratio of LCO to LO (4:1, w:w). Based on the results of solvents and emulsifiers screening, L. chuanxiong oil·Lemongrass oil 20% emulsifiable concentrate (20% LCO·LO EC) was developed, and its stability was confirmed with tests of cold and thermal storage. Field trials indicated that the insecticidal activity of the diluted 20% LCO·LO EC (1000 fold dilution) was comparable to conventional pesticide (20% imidacloprid EC) on A. citricola seven days after application. Thus, the mixture of LCO and LO has the potential to be further developed as a botanical pesticide. Full article

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Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity

by Yuan-Yuan Wang, Jun-Mian Tian, Cheng-Chen Zhang, Bo Luo and Jin-Ming Gao

Molecules 2016, 21(10), 1344; https://doi.org/10.3390/molecules21101344 - 12 Oct 2016

Cited by 13 | Viewed by 5161

Abstract

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and [...] Read more.

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriaria nepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1–3 and five semisynthetic congeners (1a–e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. Full article

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New Diphenol and Isocoumarins from the Aerial Part of Lawsonia inermis and Their Inhibitory Activities against NO Production

by Chang-Syun Yang, Hui-Chi Huang, Sheng-Yang Wang, Ping-Jyun Sung, Guan-Jhong Huang, Jih-Jung Chen and Yueh-Hsiung Kuo

Molecules 2016, 21(10), 1299; https://doi.org/10.3390/molecules21101299 - 28 Sep 2016

Cited by 16 | Viewed by 5019

Abstract

Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation [...] Read more.

Lawsonia inermis Linn (Lythraceae), also known as henna, is a small shrub or tree distributed throughout Taiwan’s Lanyu Island, in North Africa, and in Australia. Its leaves are used as a folk medicine for the treatment of external hemorrhage and fingernail abscesses. Investigation of the ethyl acetate (EtOAc)-soluble fractions from methanol extract of the aerial part of Lawsonia inermis has led to the isolation of a new diphenol, (Z)-4,4′-(prop-1-ene-1,3-diyl)diphenol (1), two new isocoumarin carbonates, inermiscarbonates A (2) and B (3), and six known compounds, 4′-hydroxyflavanone (4), apigenine (5), kampferol (6), luteolin (7), quercetin (8), and (-)-catechin (9). Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1 and 4–9 were evaluated for the inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated product of nitrite in RAW 264.7 cells with IC₅₀ values of 5.63, 15.72, 8.67, 6.67, 6.17, 7.61, and 14.52 μg/mL, respectively. Full article

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Phytochemical Compositions of Immature Wheat Bran, and Its Antioxidant Capacity, Cell Growth Inhibition, and Apoptosis Induction through Tumor Suppressor Gene

by Mi Jeong Kim, Won-Jin Yoon and Sang Sook Kim

Molecules 2016, 21(10), 1292; https://doi.org/10.3390/molecules21101292 - 27 Sep 2016

Cited by 16 | Viewed by 5885

Abstract

The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The [...] Read more.

The purpose of this study was to investigate the phytochemical compositions and antioxidant capacity, cell growth inhibition, and apoptosis induction in extracts of immature wheat bran. Immature wheat bran (IWB) was obtained from immature wheat harvested 10 days earlier than mature wheat. The phytochemical compositions of bran extract samples were analyzed by ultra-high performance liquid chromatography. The total ferulic acid (3.09 mg/g) and p-coumaric acid (75 µg/g) in IWB were significantly higher than in mature wheat bran (MWB, ferulic acid: 1.79 mg/g; p-coumaric acid: 55 µg/g). The oxygen radical absorbance capacity (ORAC: 327 µM Trolox equivalents (TE)/g) and cellular antioxidant activity (CAA: 4.59 µM Quercetin equivalents (QE)/g) of the IWB were higher than those of the MWB (ORAC: 281 µM TE/g; CAA: 0.63 µM QE/g). When assessing cell proliferation, the IWB extracts resulted in the lowest EC₅₀ values against HT-29 (18.9 mg/mL), Caco-2 (7.74 mg/mL), and HeLa cells (8.17 mg/mL) among bran extract samples. Additionally, the IWB extracts increased the gene expression of p53 and PTEN (tumor suppressor genes) in HT-29 cells, indicating inhibited cell growth and induced apoptosis through tumor suppressor genes. Full article

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Asiatic Acid Attenuates Myocardial Ischemia/Reperfusion Injury via Akt/GSK-3β/HIF-1α Signaling in Rat H9c2 Cardiomyocytes

by Xiang Huang, Li Zuo, Yanni Lv, Chuqiao Chen, Yaqin Yang, Hongbo Xin, Yunman Li and Yisong Qian

Molecules 2016, 21(9), 1248; https://doi.org/10.3390/molecules21091248 - 19 Sep 2016

Cited by 60 | Viewed by 9662

Abstract

Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this [...] Read more.

Myocardial ischemic/reperfusion injury results from severe impairment of coronary blood supply and leads to irreversible cell death, with limited therapeutic possibilities. Asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plant Centella asiatica and serves a variety of bioactivities. In this study, we determined the effect of asiatic acid on myocardial ischemia/reperfusion injury and investigated the underlying mechanisms, using an in vitro rat H9c2 cardiomyocytes model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Results showed that pre-treatment with asiatic acid significantly augmented cell viability and prevented lactate dehydrogenase (LDH) release in a concentration-dependent manner after OGD/R exposure. Asiatic acid at 10 μM effectively inhibited apoptotic cell death, suppressed the activities of caspase-3 and caspase-9, and reversed Bax/Bcl-2 ratio in hypoxic H9c2 cells. In addition, asiatic acid improved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) accumulation, enhanced mitochondrial membrane potential and decreased intracellular calcium concentration. Using Western blot assay, we found that asiatic acid promoted the phosphorylation of Akt and subsequent inactivation of glycogen synthase kinase-3β (GSK-3β), and induced the expression of hypoxia-inducible factor 1α (HIF-1α) after OGD/R. The cardioprotective effects of asiatic acid were attenuated by the Akt or HIF-1α inhibitor. Taken together, these data suggested that asiatic acid exerted protective effects against OGD/R-induced apoptosis in cardiomyocytes, at least partly via the Akt/GSK-3β/HIF-1α pathway. Full article

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Open AccessArticle

Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria

by Malena E. Skogman, Sonja Kanerva, Suvi Manner, Pia M. Vuorela and Adyary Fallarero

Molecules 2016, 21(9), 1211; https://doi.org/10.3390/molecules21091211 - 10 Sep 2016

Cited by 47 | Viewed by 13027

Abstract

Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors [...] Read more.

Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors from natural compound libraries. In this system, QS is correlated with the production of violacein, which is directly controlled by the LuxI/LuxR system in Chromobacterium violaceum ATCC 31532. The parallel use of C. violaceum Tn5-mutant CV026, which depends on auto-inducer addition, allows simultaneous discrimination of compounds that act as quenchers of the AHL signal (quorum quenchers). The incorporation of a redox stain into the platform allowed further distinction between QS inhibitors, quorum quenchers and antibacterial compounds. A pilot screening was performed with 465 natural and synthetic flavonoids. All the most active compounds were flavones and they displayed potencies (IC₅₀) in the range of 3.69 to 23.35 μM. These leads were particularly promising as they inhibited the transition from microcolonies into mature biofilms from Escherichia coli and Pseudomonas aeruginosa strains. This approach can be very effective in identifying new antimicrobials posing lesser risks of resistance. Full article

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Chemical and Antioxidant Properties of Wild Edible Mushrooms from Native Nothofagus spp. Forest, Argentina

by Carolina V. Toledo, Carolina Barroetaveña, Ângela Fernandes, Lillian Barros and Isabel C. F. R. Ferreira

Molecules 2016, 21(9), 1201; https://doi.org/10.3390/molecules21091201 - 8 Sep 2016

Cited by 52 | Viewed by 10421

Abstract

This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied [...] Read more.

This study addresses issues regarding chemical and bioactive properties of nine wild edible mushrooms from native Nothofagus forest from Patagonia, Argentina. Macronutrients, sugars, fatty acids, tocopherols, organic acids, phenolic compounds and antioxidant properties were determined. Protein was found in high levels and varied between 3.35 g/100 g dw in Cyttaria hariotii and 22.29 g/100 g dw in Lepista nuda. All of them presented mannitol and trehalose as main sugars. Mannitol was significantly higher in Ramaria patagonica, although absent in Fistulina endoxantha, whereas trehalose predominated in Aleurodiscus vitellinus, Hydropus dusenii, Cortinarius magellanicus, C. hariotii, Grifola gargal and L. nuda, ranging from 1.15 to 10.26 g/100 g dw; it was absent in R. patagonica. The major fatty acid found was linoleic acid, followed by oleic acid and palmitic acid. All species presented oxalic and fumaric acids, while some also had malic, quinic and citric acids. Tocopherols composition was variable. Cortinarius magellanicus presented significantly higher contents of both α-tocopherol and β-tocopherol. R. patagonica presented the best results in all the antioxidant activity assays (EC₅₀ values ≤ 1 mg/mL) and the highest content of phenolic compounds presenting gallic, p-hydroxybenzoic, p-coumaric and cinnamic acids. This study constitutes the first report on chemical composition and nutritional value of most of these edible mushroom species. Furthermore, it provides important information necessary to characterize and define the use of these species as gastronomic delicacies, functional foods and sources of bioactive compounds. Full article

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Characterization of a New Flavone and Tyrosinase Inhibition Constituents from the Twigs of Morus alba L.

by Long Zhang, Guanjun Tao, Jie Chen and Zong-Ping Zheng

Molecules 2016, 21(9), 1130; https://doi.org/10.3390/molecules21091130 - 2 Sep 2016

Cited by 56 | Viewed by 8851

Abstract

The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 2–17 were [...] Read more.

The twigs of Morus alba L. were found to show strong tyrosinase inhibition activity, and the responsible active components in the extract were further investigated in this study. A flavone, named morusone (1), and sixteen known compounds 2–17 were isolated from M. alba twigs and their structures were identified by interpretation of the corresponding ESI-MS and NMR spectral data. In the tyrosinase inhibitory test, the compounds steppogenin (IC₅₀ 0.98 ± 0.01 µM), 2,4,2′,4′-tetrahydroxychalcone (IC₅₀ 0.07 ± 0.02 µM), morachalcone A (IC₅₀ 0.08 ± 0.02 µM), oxyresveratrol (IC₅₀ 0.10 ± 0.01 µM), and moracin M (8.00 ± 0.22 µM) exhibited significant tyrosinase inhibition activities, much stronger than that of the positive control kojic acid. These results suggest that M. alba twig extract should served as a good source of natural tyrosinase inhibitors for use in foods as antibrowning agents or in cosmetics as skin-whitening agents. Full article

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Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts and α-Glucosidase Inhibitory Activities of Different Fractionations

by Shuxia Yan, Xianan Zhang, Xin Wen, Qiang Lv, Changjie Xu, Chongde Sun and Xian Li

Molecules 2016, 21(9), 1148; https://doi.org/10.3390/molecules21091148 - 31 Aug 2016

Cited by 29 | Viewed by 8415

Abstract

Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside [...] Read more.

Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak^® cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC₅₀ = 15.4–69.5 μg/mL), which were higher than that of positive control acarbose (IC₅₀ = 383.2 μg/mL). Four purified compounds 1–4 exerted α-glucosidase inhibitory activities, with IC₅₀ values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved. Full article

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Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes

by Yo-Han Han, Ji-Ye Kee, Dae-Seung Kim, Jeong-geon Mun, Mi-Young Jeong, Sang-Hyun Park, Byung-Min Choi, Sung-Joo Park, Hyun-Jung Kim, Jae-Young Um and Seung-Heon Hong

Molecules 2016, 21(9), 1135; https://doi.org/10.3390/molecules21091135 - 27 Aug 2016

Cited by 38 | Viewed by 9511

Abstract

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a [...] Read more.

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, β-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis. Full article

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Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

by Lamiaa A. Shaala, Diaa T. A. Youssef, Jihan M. Badr and Steve M. Harakeh

Molecules 2016, 21(9), 1116; https://doi.org/10.3390/molecules21091116 - 24 Aug 2016

Cited by 36 | Viewed by 6057

Abstract

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H [...] Read more.

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC₅₀ of 1.5 μg/mL, while 1–10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives. Full article

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Open AccessArticle

Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization

by Aline Fleck, Patrik F. G. Cabral, Felipe F. M. Vieira, Deo A. Pinheiro, Carlos R. Pereira, Wilson C. Santos and Thelma B. Machado

Molecules 2016, 21(8), 1059; https://doi.org/10.3390/molecules21081059 - 22 Aug 2016

Cited by 26 | Viewed by 8905

Abstract

The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the [...] Read more.

The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the effect produced by a magistral formulation of ethanolic extracts of Punica granatum peels on a non-healing chronic ulcer. The complete closure of the chronic ulcer that was initially not responsive to standard medical care was observed. A 2% (w/w) P. granatum peels ethanolic extract hydrogel-based formulation (PGHF) was standardized and subjected to physicochemical studies to establish the quality control parameters using, among others, assessment criteria such as optimum appearance, pH range, viscosity and hydrogel disintegration. The stability and quantitative chromatographic data was assessed in storage for six months under two temperature regimes. An efficient HPLC-DAD method was established distinguishing the biomarkers punicalin and punicalagin simultaneously in a single 8 min run. PGHF presented suitable sensorial and physicochemical performance, showing that punicalagin was not significantly affected by storage (p > 0.05). Formulations containing extracts with not less than 0.49% (w/w) total punicalagin might find good use in wound healing therapy. Full article

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Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia quinata

by Jin-Pyo An, Thi Kim Quy Ha, Jinwoong Kim, Tae Oh Cho and Won Keun Oh

Molecules 2016, 21(8), 1091; https://doi.org/10.3390/molecules21081091 - 19 Aug 2016

Cited by 29 | Viewed by 6817

Abstract

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B [...] Read more.

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2–14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC₅₀ values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 μM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC₅₀ values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 μM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents. Full article

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Open AccessArticle

Antibacterial Activity and Membrane-Disruptive Mechanism of 3-p-trans-Coumaroyl-2-hydroxyquinic Acid, a Novel Phenolic Compound from Pine Needles of Cedrus deodara, against Staphylococcus aureus

by Yanping Wu, Jinrong Bai, Kai Zhong, Yina Huang, Huayi Qi, Yan Jiang and Hong Gao

Molecules 2016, 21(8), 1084; https://doi.org/10.3390/molecules21081084 - 18 Aug 2016

Cited by 130 | Viewed by 7970

Abstract

Recently, we reported that a novel phenolic compound isolated from Cedrus deodara, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA), exhibits a potent antioxidant activity. The present study aimed to evaluate the antibacterial activity of CHQA against eleven food-borne pathogens and to elucidate [...] Read more.

Recently, we reported that a novel phenolic compound isolated from Cedrus deodara, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA), exhibits a potent antioxidant activity. The present study aimed to evaluate the antibacterial activity of CHQA against eleven food-borne pathogens and to elucidate its mechanism of action against Staphylococcus aureus. The results from minimum inhibitory concentration (MIC) determinations showed that CHQA exhibited moderate inhibitory effects on all of the tested pathogens with MIC values ranging from 2.5–10 mg/mL. Membrane potential measurements and flow cytometric analysis demonstrated that CHQA damaged the cytoplasmic membrane of S. aureus, causing a significant membrane hyperpolarization with a loss of membrane integrity. Moreover, CHQA induced an increase in membrane fluidity and conformational changes in membrane protein of S. aureus, suggesting that CHQA probably acts on the cell membrane by interactions with membrane lipid and protein. Transmission electron microscopic observations further confirmed that CHQA disrupted the cell membrane of S. aureus and caused severe morphological changes, which even led to leakage of intracellular constituents. These findings indicated that CHQA could have the potential to serve as a natural antibacterial agent to control and prevent the growth of pathogens in food and in food-processing environments. Full article

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Open AccessArticle

Steroidal Saponins from the Rhizomes of Anemarrhena asphodeloides

by Bing-You Yang, Jing Zhang, Yan Liu and Hai-Xue Kuang

Molecules 2016, 21(8), 1075; https://doi.org/10.3390/molecules21081075 - 17 Aug 2016

Cited by 22 | Viewed by 6096

Abstract

Four new steroid saponins 1–4 were isolated from the rhizomes of Anemarrhena asphodeloides (Asparagaceae), as well as four known saponins: anemarsaponin B (5) timosaponin D (6), timosaponin E1 (7) anemarsaponin B II (8). [...] Read more.

Four new steroid saponins 1–4 were isolated from the rhizomes of Anemarrhena asphodeloides (Asparagaceae), as well as four known saponins: anemarsaponin B (5) timosaponin D (6), timosaponin E1 (7) anemarsaponin B II (8). Their structures were established through UV and NMR as well as MS data. All the compounds were evaluated for cytotoxicity against HepG2 and SGC7901 human cancer lines. Compounds 3 and 7 displayed medium antiproliferative activities on HepG2 and SGC7901 cells, with IC₅₀ values of 43.90 and 57.90 μM, respectively. Full article

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Phytochemical Profile and Evaluation of the Biological Activities of Essential Oils Derived from the Greek Aromatic Plant Species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita

by Eleni Fitsiou, Gregoria Mitropoulou, Katerina Spyridopoulou, Angeliki Tiptiri-Kourpeti, Manolis Vamvakias, Haido Bardouki, Mihalis Ι. Panayiotidis, Alex Galanis, Yiannis Kourkoutas, Katerina Chlichlia and Aglaia Pappa

Molecules 2016, 21(8), 1069; https://doi.org/10.3390/molecules21081069 - 16 Aug 2016

Cited by 104 | Viewed by 15006

Abstract

Natural products, known for their medicinal properties since antiquity, are continuously being studied for their biological properties. In the present study, we analyzed the composition of the volatile preparations of essential oils of the Greek plants Ocimum basilicum (sweet basil), Mentha spicata (spearmint), [...] Read more.

Natural products, known for their medicinal properties since antiquity, are continuously being studied for their biological properties. In the present study, we analyzed the composition of the volatile preparations of essential oils of the Greek plants Ocimum basilicum (sweet basil), Mentha spicata (spearmint), Pimpinella anisum (anise) and Fortunella margarita (kumquat). GC/MS analyses revealed that the major components in the essential oil fractions, were carvone (85.4%) in spearmint, methyl chavicol (74.9%) in sweet basil, trans-anethole (88.1%) in anise, and limonene (93.8%) in kumquat. We further explored their biological potential by studying their antimicrobial, antioxidant and antiproliferative activities. Only the essential oils from spearmint and sweet basil demonstrated cytotoxicity against common foodborne bacteria, while all preparations were active against the fungi Saccharomyces cerevisiae and Aspergillus niger. Antioxidant evaluation by DPPH and ABTS radical scavenging activity assays revealed a variable degree of antioxidant potency. Finally, their antiproliferative potential was tested against a panel of human cancer cell lines and evaluated by using the sulforhodamine B (SRB) assay. All essential oil preparations exhibited a variable degree of antiproliferative activity, depending on the cancer model used, with the most potent one being sweet basil against an in vitro model of human colon carcinoma. Full article

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Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

by Muhammad Tayyab Akhtar, Mohamad Syakir Bin Mohd Sarib, Intan Safinar Ismail, Faridah Abas, Amin Ismail, Nordin Hj Lajis and Khozirah Shaari

Molecules 2016, 21(8), 1026; https://doi.org/10.3390/molecules21081026 - 9 Aug 2016

Cited by 34 | Viewed by 13313

Abstract

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat [...] Read more.

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract. Full article

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Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines

by Omar Aristeo Peña-Morán, María Luisa Villarreal, Laura Álvarez-Berber, Angélica Meneses-Acosta and Verónica Rodríguez-López

Molecules 2016, 21(8), 1013; https://doi.org/10.3390/molecules21081013 - 4 Aug 2016

Cited by 174 | Viewed by 7677

Abstract

Despite prevention and treatment options, breast cancer (BC) has become one of the most important issues in the present day. Therefore, the need for more specific and efficient compounds remains paramount. We evaluated four previously isolated aryltetralin lignans: 5′-demethoxy-β-peltatin-A-methylether (1), acetylpodophyllotoxin [...] Read more.

Despite prevention and treatment options, breast cancer (BC) has become one of the most important issues in the present day. Therefore, the need for more specific and efficient compounds remains paramount. We evaluated four previously isolated aryltetralin lignans: 5′-demethoxy-β-peltatin-A-methylether (1), acetylpodophyllotoxin (2), 5′-demethoxydeoxypodophyllotoxin (3), and 7′,8′-dehydroacetylpodophyllotoxin (4) for cytotoxicity, clonogenicity, and selectivity against three BC cell lines: MCF-7, MDA-MB-231, and BT-549, as well as the non-tumorigenic mammary epithelial cell line MCF-10A. Cytotoxicity was evaluated after 72 h of treatment, and clonogenicity was determined at 72 h post-treatment; experiments were performed using the sulforhodamine B staining assay. Selective-index (SI) was calculated by comparing pure compound IC₅₀ values in MCF-10A cell line against the IC₅₀ of the same compound in cancer cell lines. Structural similarities among lignans and controls (podophyllotoxin and etoposide) were analyzed using the Tanimoto coefficient (Tc). Lignans were cytotoxic against all tested cell lines (0.011–7.22 µM) and clonogenicity testing showed a dose-dependent cytocidality for all lignans (≥0.08 µg/mL); compounds 2 and 3 were more potent (14.1 and 7.6 respectively) than etoposide in BT-549 cell line, while compound 2 displayed selectivity (SI = 28.17) in BT-549 cell line. Tc values of lignans suggested a greater similarity with podophyllotoxin structure. Full article

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Open AccessArticle

Characterization and Analysis of 2-(2-Phenylethyl)-chromone Derivatives from Agarwood (Aquilaria crassna) by Artificial Holing for Different Times

by Jin Ling Yang, Wen Hua Dong, Fan Dong Kong, Ge Liao, Jun Wang, Wei Li, Wen Li Mei and Hao Fu Dai

Molecules 2016, 21(7), 911; https://doi.org/10.3390/molecules21070911 - 13 Jul 2016

Cited by 33 | Viewed by 6395

Abstract

A total of fifty-six chromones, including seven 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones (THPECs), five 5,6-epoxy-2-(2-phenylethyl)chromones (EPECs), seven 5,6:7,8-diepoxy-2-(2-phenylethyl)chromones (DEPECs) and thirty-seven 2-(2-phenylethyl)chromones of the flidersia type (FTPECs), were characterized by HPLC/DAD/ESI/MS/MS in three agarwood samples (from Aquilaria crassna) induced by artificial holing with different holing times. [...] Read more.

A total of fifty-six chromones, including seven 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones (THPECs), five 5,6-epoxy-2-(2-phenylethyl)chromones (EPECs), seven 5,6:7,8-diepoxy-2-(2-phenylethyl)chromones (DEPECs) and thirty-seven 2-(2-phenylethyl)chromones of the flidersia type (FTPECs), were characterized by HPLC/DAD/ESI/MS/MS in three agarwood samples (from Aquilaria crassna) induced by artificial holing with different holing times. The characteristic fragmentation behavior of DEPECs and EPECs, and the methods to distinguish these four types of chromones by MS analysis were described for the first time. In addition, it was found that the relative contents of DEPECs and EPECs were down-regulated, while the relative contents of THPECs and FTPECs were up-regulated for the samples from two, four and five years of the agarwood formation time. However, the relative contents of six most widespread and abundant FTPECs presented roughly upward based on the formation time. These results could be referenced to distinguish different agarwood samples collected from different formation time. Full article

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Ellagitannins from Raspberry (Rubus idaeus L.) Fruit as Natural Inhibitors of Geotrichum candidum

by Elżbieta Klewicka, Michał Sójka, Robert Klewicki, Krzysztof Kołodziejczyk, Lidia Lipińska and Adriana Nowak

Molecules 2016, 21(7), 908; https://doi.org/10.3390/molecules21070908 - 13 Jul 2016

Cited by 37 | Viewed by 7963

Abstract

The paper presents the chemical characteristics of ellagitannins isolated from raspberry (Rubus idaeus L.) fruit and their in vitro and in situ antifungal activity against Geotrichum candidum ŁOCK 0511. The study investigated a complex preparation containing various raspberry ellagitannins at a concentration [...] Read more.

The paper presents the chemical characteristics of ellagitannins isolated from raspberry (Rubus idaeus L.) fruit and their in vitro and in situ antifungal activity against Geotrichum candidum ŁOCK 0511. The study investigated a complex preparation containing various raspberry ellagitannins at a concentration of 86% w/w, as well as pure lambertianin C and sanguiin H-6. The ellagitannin preparation was obtained by extracting raspberry press cake and purifying the extract using Amberlite XAD resin, while individual compounds were isolated by means of preparative HPLC. The complex preparation was analyzed for the content of ellagitannins, anthocyanins, and flavan-3-ols using HPLC and LC-MS. The antifungal activity of the complex ellagitannin preparation and the isolated ellagitannins was determined for the strain Geotrichum candidum. The MIC and MFC values (10.0 mg/mL and 30.0 mg/mL, respectively) were found to be the same for lambertianin C, sanguiin H-6, and the complex ellagitannin preparation. The fungistatic activity of the studied ellagitannin preparation at a concentration of 10 mg/mL, as determined by the poisoned medium method, was 65.2% following 6 day incubation of Geotrichum candidum, with the linear growth rate of only 16.2 mm/day. The corresponding parameters for the control sample were 0% and 56 mm/day, respectively. The study demonstrated both in vitro and in situ antifungal activity of raspberry ellagitannins against Geotrichum candidum. Full article

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Open AccessArticle

Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity

by Fahad A. Al-Abbasi, Eman A. Alghamdi, Mohammed A. Baghdadi, Abdulmohsin J. Alamoudi, Ali M. El-Halawany, Hany M. El-Bassossy, Ali H. Aseeri and Ahmed M. Al-Abd

Molecules 2016, 21(7), 886; https://doi.org/10.3390/molecules21070886 - 8 Jul 2016

Cited by 44 | Viewed by 8954

Abstract

Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant [...] Read more.

Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl₄-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC₅₀ values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG₂ and Huh7, cells decreasing its IC₅₀s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G₂/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G₂/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM) was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics. Full article

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Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans

by Pille Link, Kevin Roth, Frank Sporer and Michael Wink

Molecules 2016, 21(7), 871; https://doi.org/10.3390/molecules21070871 - 2 Jul 2016

Cited by 29 | Viewed by 7089

Abstract

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in [...] Read more.

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect. Full article

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Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison

by Weizhe Xu, Yan Zhao, Yi Qin, Beikang Ge, Wenwen Gong, Yingting Wu, Xiaorong Li, Yuming Zhao, Pingxiang Xu and Ming Xue

Molecules 2016, 21(7), 874; https://doi.org/10.3390/molecules21070874 - 1 Jul 2016

Cited by 18 | Viewed by 6052

Abstract

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin [...] Read more.

There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography–mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and C_max of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage. Full article

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Open AccessArticle

Essential Oil Variation from Twenty Two Genotypes of Citrus in Brazil—Chemometric Approach and Repellency Against Diaphorina citri Kuwayama

by Moacir Dos Santos Andrade, Leandro Do Prado Ribeiro, Paulo Cesar Borgoni, Maria Fátima das Graças Fernandes da Silva, Moacir Rossi Forim, João Batista Fernandes, Paulo Cezar Vieira, José Djair Vendramin and Marcos Antônio Machado

Molecules 2016, 21(6), 814; https://doi.org/10.3390/molecules21060814 - 22 Jun 2016

Cited by 11 | Viewed by 7959

Abstract

The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities [...] Read more.

The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities include the synthesis of (Z)-β-ocimene and (E)-caryophyllene for all 11 genotypes of group A. Genotypes of group B are not uniformly characterized by essential oil compounds. When stimulated with odor sources of 22 genotypes in a Y-tube olfactometer D. citri preferentially entered the arm containing the volatile oils of Murraya paniculata, confirming orange jasmine as its best host. C. reticulata × C. sinensis was the least preferred genotype, and is characterized by the presence of phytol, (Z)-β-ocimene, and β-elemene, which were not found in the most preferred genotype. We speculate that these three compounds may act as a repellent, making these oils less attractive to D. citri. Full article

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Antioxidative, Antibacterial, and Food Functional Properties of the Half-Fin Anchovy Hydrolysates-Glucose Conjugates Formed via Maillard Reaction

by Ru Song, Peiyu Yang, Rongbian Wei and Guanqiang Ruan

Molecules 2016, 21(6), 795; https://doi.org/10.3390/molecules21060795 - 20 Jun 2016

Cited by 28 | Viewed by 7197

Abstract

The antioxidative, antibacterial, and food functional properties of the half-fin anchovy hydrolysates (HAHp)-glucose conjugates formed by Maillard reaction (MR) were investigated, respectively. Results of sugar and amino acid contents loss rates, browning index, and molecular weight distribution indicated that the initial pH of [...] Read more.

The antioxidative, antibacterial, and food functional properties of the half-fin anchovy hydrolysates (HAHp)-glucose conjugates formed by Maillard reaction (MR) were investigated, respectively. Results of sugar and amino acid contents loss rates, browning index, and molecular weight distribution indicated that the initial pH of HAHp played an important role in the process of MR between HAHp and glucose. HAHp-glucose Maillard reaction products (HAHp-G MRPs) demonstrated enhanced antioxidative activities of reducing power and scavenging DPPH radicals compared to control groups. HAHp-G MRPs produced from the condition of pH 9.6 displayed the strongest reducing power. The excellent scavenging activity on DPPH radicals was found for HAHp(5.6)-G MRPs which was produced at pH 5.6. Additionally, HAHp(5.6)-G MRPs showed variable antibacterial activities against Escherichia coli, Pseudomonas fluorescens, Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium, and Sarcina lutea, with the MIC values ranging from 8.3 to 16.7 μg/mL. Result of scanning electron microscopy (SEM) on E. coli suggested that HAHp(5.6)-G MRPs exhibited antibacterial activity by destroying the cell integrity through membrane permeabilization. Moreover, HAHp(5.6)-G MRPs had excellent foaming ability and stability at alkaline conditions of pH 8.0, and showed emulsion properties at acidic pH 4.0. These results suggested that specific HAHp-G MRPs should be promising functional ingredients used in foods. Full article

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High-Resolution α-Glucosidase Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of Antidiabetic Compounds in Eremanthus crotonoides (Asteraceae)

by Eder Lana e Silva, Jonathas Felipe Revoredo Lobo, Joachim Møllesøe Vinther, Ricardo Moreira Borges and Dan Staerk

Molecules 2016, 21(6), 782; https://doi.org/10.3390/molecules21060782 - 16 Jun 2016

Cited by 31 | Viewed by 7490

Abstract

α-Glucosidase inhibitors decrease the cleavage- and absorption rate of monosaccharides from complex dietary carbohydrates, and represent therefore an important class of drugs for management of type 2 diabetes. In this study, a defatted ethyl acetate extract of Eremanthus crotonoides leaves with an inhibitory [...] Read more.

α-Glucosidase inhibitors decrease the cleavage- and absorption rate of monosaccharides from complex dietary carbohydrates, and represent therefore an important class of drugs for management of type 2 diabetes. In this study, a defatted ethyl acetate extract of Eremanthus crotonoides leaves with an inhibitory concentration (IC₅₀) of 34.5 μg/mL towards α-glucosidase was investigated by high-resolution α-glucosidase inhibition profiling combined with HPLC-HRMS-SPE-NMR. This led to identification of six α-glucosidase inhibitors, namely quercetin (16), trans-tiliroside (17), luteolin (19), quercetin-3-methyl ether (20), 3,5-di-O-caffeoylquinic acid n-butyl ester (26) and 4,5-di-O-caffeoylquinic acid n-butyl ester (29). In addition, nineteen other metabolites were identified. The most active compounds were the two regioisomeric di-O-caffeoylquinic acid derivatives 26 and 29, with IC₅₀ values of 5.93 and 5.20 μM, respectively. This is the first report of the α-glucosidase inhibitory activity of compounds 20, 26, and 29, and the findings support the important role of Eremanthus species as novel sources of new drugs and/or herbal remedies for treatment of type 2 diabetes. Full article

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Inhibition of Advanced Glycation End-Product Formation and Antioxidant Activity by Extracts and Polyphenols from Scutellaria alpina L. and S. altissima L.

by Izabela Grzegorczyk-Karolak, Krzysztof Gołąb, Jakub Gburek, Halina Wysokińska and Adam Matkowski

Molecules 2016, 21(6), 739; https://doi.org/10.3390/molecules21060739 - 14 Jun 2016

Cited by 81 | Viewed by 8925

Abstract

Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina, [...] Read more.

Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power), antiradical (DPPH) and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 μg/mL), followed by luteolin (85.4%). Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively). The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders. Full article

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Open AccessArticle

Effects of Flavonoids in Lysimachia clethroides Duby on the Activities of Cytochrome P450 CYP2E1 and CYP3A4 in Rat Liver Microsomes

by Zhi-Juan Zhang, Zhao-Yang Xia, Jin-Mei Wang, Xue-Ting Song, Jin-Feng Wei and Wen-Yi Kang

Molecules 2016, 21(6), 738; https://doi.org/10.3390/molecules21060738 - 14 Jun 2016

Cited by 16 | Viewed by 6113

Abstract

Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at [...] Read more.

Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at different concentrations were added to the incubation systems. After incubation, a validated high performance liquid chromatography (HPLC) method was applied to separate and determine the relevant metabolites. The results suggested that kaempferol exhibited a weak inhibition of CYP2E1 activity with an IC₅₀ of 60.26 ± 2.54 μM, while quercetin and kaempferol caused a moderate inhibition of CYP3A4 activity with IC₅₀ values of 18.77 ± 1.69 μM and 32.65 ± 1.32 μM, respectively. Isoquercitrin and astragalin had no effects on the activities of either CYP2E1 or CYP3A4. It could be speculated from these results that the inhibitory effects of quercetin and kaempferol on the activities of CYP2E1 and CYP3A4 could be the mechanisms underlying the hepatoprotective effects of L. clethroides. Full article

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Anticoagulant Activity and Structural Characterization of Polysaccharide from Abalone (Haliotis discus hannai Ino) Gonad

by Jun Zhao, Jingfeng Yang, Shuang Song, Dayong Zhou, Weizhou Qiao, Ce Zhu, Shuyin Liu and Beiwei Zhu

Molecules 2016, 21(6), 697; https://doi.org/10.3390/molecules21060697 - 8 Jun 2016

Cited by 25 | Viewed by 6418

Abstract

In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction [...] Read more.

In this study, we aimed at characterizing the structure and the anticoagulant activity of a polysaccharide fraction (AGP33) isolated from the gonads of Haliotis discus hannai Ino. AGP33 was extracted by enzymatic hydrolysis and purified by ion-exchange and gel-filtration chromatography. The backbone fraction of AGP33 (BAGP33), which appeared to contain of mannose, glucose and galactose, was prepared by partial acid hydrolysis. According to methylation and nuclear magnetic resonance (NMR) spectroscopy, the backbone of AGP33 was identified as mainly consisting of 1→3-linked, 1→4-linked, and 1→6-linked monosaccharides. AGP33 is a sulfated polysaccharide with sulfates occur at 3-O- and 4-O-positions. It prolonged thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) compared to a saline control solution in a dosage-dependent manner. AGP33 exhibited an extension (p < 0.01) of APTT compared to the saline group at concentrations higher than 5 μg/mL. AGP33 exhibited higher anticoagulant activity than its desulfated product (AGP33-des) and BAGP33. The results showed that polysaccharide with higher molecular weight and sulfate content demonstrated greater anticoagulant activity. Full article

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Eriobotrya japonica Water Extract Characterization: An Inducer of Interferon-Gamma Production Mainly by the JAK-STAT Pathway

by Khalid Z. Matalka, Nada A. Abdulridha, Mujtaba M. Badr, Kenza Mansoor, Nidal A. Qinna and Fadi Qadan

Molecules 2016, 21(6), 722; https://doi.org/10.3390/molecules21060722 - 2 Jun 2016

Cited by 13 | Viewed by 7372

Abstract

Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were [...] Read more.

Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were performed on the water extract to investigate specific cytokines’ modulation. These earlier studies, however, have shown that EJ leaf water extract (WE) and the water phase (WP) induce cytokines’ production in in vitro and in vivo models. Therefore, the aim of this study was to specify the group(s) of compounds in EJ leaves that have this immunomodulatory activity and their mechanism of action. WE was obtained from boiling the leaves followed by butanol extraction, yielding a butanol-water phase (WP). WP was then subjected to methanol:acetone fractionation, yielding upper (MAU) and lower (MAL) phases. For further fractionation, MAU was subjected to column chromatography followed by elution with ethanol:water (EW), methanol:ethanol (ME) and, lastly, acetone:water (AW), respectively, to reveal three sub-fractions; MAU-EW, MAU-ME and MAU-AW. MAU-AW significantly increased IFN-γ production from unstimulated and stimulated mouse spleen cells, as well as CD3+ T cells and natural killer cells. Furthermore, the fold increase of IFN-γ production by MAU-AW was concentration dependent, higher than the parent extract or any of the other sub-fractions, and such an IFN-γ increase was reversed by two JAK-STAT inhibitors. In addition, MALDI-TOF-MS analysis of the extracts and sub-fractions showed compounds with molecular weights of >500 Daltons. The MAU-AW sub-fraction contained more polar compounds, such as flavonol and caffeic glycosides. In conclusion, these polar compounds in the EJ extract are responsible for inducing IFN-γ production. Further chemical elucidation is warranted to lead to a specific IFN-γ inducer and an immunomodulator in polarizing immune cells and balancing immune responses in certain diseases. Full article

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Phenolic Profile and Antioxidant Potential of Leaves from Selected Cotoneaster Medik. Species

by Agnieszka Kicel, Piotr Michel, Aleksandra Owczarek, Anna Marchelak, Dorota Żyżelewicz, Grażyna Budryn, Joanna Oracz and Monika Anna Olszewska

Molecules 2016, 21(6), 688; https://doi.org/10.3390/molecules21060688 - 26 May 2016

Cited by 26 | Viewed by 7150

Abstract

The antioxidant efficiency of 70% aqueous methanolic extracts from the leaves of twelve selected Cotoneaster Medik. species was evaluated using four complementary in vitro tests based on SET- (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms (DPPH, FRAP, O₂^•− and [...] Read more.

The antioxidant efficiency of 70% aqueous methanolic extracts from the leaves of twelve selected Cotoneaster Medik. species was evaluated using four complementary in vitro tests based on SET- (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms (DPPH, FRAP, O₂^•− and H₂O₂ scavenging assays). The samples exhibited the dose-dependent responses in all assays with activity parameters of EC₅₀ = 18.5–34.5 µg/mL for DPPH; 0.9–3.8 mmol Fe²⁺/g for FRAP; SC₅₀ = 27.7–74.8 µg/mL for O₂^•−; and SC₅₀ = 29.0–91.3 µg/mL for H₂O₂. Significant linear correlations (|r| = 0.76–0.97, p < 0.01) between activity parameters and total contents of phenolics (5.2%–15.4% GAE) and proanthocyanidins (2.1%–15.0% CYE), with weak or no effects for chlorogenic acid isomers (0.69%–2.93%) and total flavonoids (0.28%–1.40%) suggested that among the listed polyphenols, proanthocyanidins are the most important determinants of the tested activity. UHPLC-PDA-ESI-QTOF-MS analyses led to detection of 34 polyphenols, of which 10 B-type procyanidins, 5 caffeoylquinic acids and 14 flavonoids were identified. After cluster analysis of the data matrix, the leaves of Cotoneaster zabelii, C. splendens, C. bullatus, C. divaricatus, C. hjelmqvistii and C. lucidus were selected as the most promising sources of natural antioxidants, exhibiting the highest phenolic levels and antioxidant capacities, and therefore the greatest potential for pharmaceutical applications. Full article

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A New Canthinone-Type Alkaloid Isolated from Ailanthus altissima Swingle

by Hye Mi Kim, Jin Su Lee, Jurdas Sezirahiga, Jaeyoung Kwon, Miran Jeong, Dongho Lee, Jung-Hye Choi and Dae Sik Jang

Molecules 2016, 21(5), 642; https://doi.org/10.3390/molecules21050642 - 16 May 2016

Cited by 41 | Viewed by 7319

Abstract

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2–6). Moreover, [...] Read more.

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2–6). Moreover, four phenyl propanoids (7–10), two lignans (11 and 12), two triterpenoids (13 and 14) and a fatty acid (15) having previously known chemical structures were isolated during the same course of this study. The structure of the new compound was elucidated by physical (m.p., [α]_D) and spectroscopic data (¹H-NMR, ¹³C-NMR, 2D NMR, and HR-DART-MS) interpretation and its absolute configuration was determined by electronic circular dichroism (ECD) data and quantum chemical calculations. The inflammatory activities of the isolates were screened on lipopolysaccharide (LPS)-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells. Among these isolated compounds, six compounds exhibited significant inhibition of NO production, with IC₅₀ values in the range of 5.92 ± 0.9 to 15.09 ± 1.8 μM. Full article

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Protective Effects of Dihydromyricetin against •OH-Induced Mesenchymal Stem Cells Damage and Mechanistic Chemistry

by Xican Li, Jingjing Liu, Jian Lin, Tingting Wang, Jieyuan Huang, Yongqiang Lin and Dongfeng Chen

Molecules 2016, 21(5), 604; https://doi.org/10.3390/molecules21050604 - 9 May 2016

Cited by 37 | Viewed by 6981

Abstract

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for [...] Read more.

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for cell transplantation therapy. Mechanistic chemistry studies indicated that compared with myricetin, DHM was less effective at ABTS⁺• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical) scavenging and reducing Cu²⁺, and had higher •O₂⁻ and DPPH• (1,1-diphenyl-2-picrylhydrazyl radical) scavenging activities. Additionally, DHM could also chelate Fe²⁺ to give an absorption maximum at 589 nm. Hence, such protective effect of DHM may arise from its antioxidant activities which are thought to occur via direct radical-scavenging and Fe²⁺-chelation. Direct radical-scavenging involves an electron transfer (ET) pathway. The hydrogenation of the 2,3-double bond is hypothesized to reduce the ET process by blocking the formation of a larger π-π conjugative system. The glycosidation of the 3–OH in myricitrin is assumed to sterically hinder atom transfer in the •O₂⁻ and DPPH• radical-scavenging processes. In DHM, the Fe²⁺-chelating effect can actually be attributed to the 5,3′,4′,5′–OH and 4–C=O groups, and the 3–OH group itself can neither scavenge radicals nor chelate metal. Full article

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An Aqueous Extract of Tuberaria lignosa Inhibits Cell Growth, Alters the Cell Cycle Profile, and Induces Apoptosis of NCI-H460 Tumor Cells

by Joana M. Pereira, Vanessa Lopes-Rodrigues, Cristina P. R. Xavier, M. João Lima, Raquel T. Lima, Isabel C. F. R. Ferreira and M. Helena Vasconcelos

Molecules 2016, 21(5), 595; https://doi.org/10.3390/molecules21050595 - 6 May 2016

Cited by 11 | Viewed by 5836

Abstract

Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared [...] Read more.

Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared by infusion and decoction) was investigated in three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and HCT-15 (human colorectal adenocarcinoma). Both extracts inhibited the growth of these cell lines; the most potent one being the T. lignosa extract obtained by infusion in the NCI-H460 cells (GI₅₀ of approximately 50 μg/mL). Further assays were carried out with this extract in NCI-H460 cells. At 100 μg/mL or 150 μg/mL it caused an increase in the percentage of cells in the G0/G1 phase and a decrease of cells in S phase of the cell cycle. Additionally, these concentrations caused an increase in the percentage of apoptotic cells. In agreement, a decrease in total poly (ADP-ribose) polymerase (PARP) and pro-caspase 3 levels was found. In conclusion, the T. lignosa extract obtained by infusion was more potent in NCI-H460 cells, altering the cell cycle progression and inducing apoptosis. This work highlights the importance of T. lignosa as a source of bioactive compounds with tumor cell growth inhibitory potential. Full article

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Antimicrobial Activity and Chromatographic Analysis of Extracts from Tropaeolum pentaphyllum Lam. Tubers

by Ritiel Corrêa Da Cruz, Laura Bedin Denardi, Natalia Jank Mossmann, Mariana Piana, Sydney Hartz Alves and Marli Matiko Anraku De Campos

Molecules 2016, 21(5), 566; https://doi.org/10.3390/molecules21050566 - 28 Apr 2016

Cited by 7 | Viewed by 6795

Abstract

Background: Tropaeolum pentaphyllum Lam. tubers (Tropaeolaceae) are known and used as a condiment and for the treatment of skin infections in Southern Brazil. However, its activity and composition has not yet been investigated. Thus, different extracts and the essential oil from the tubers [...] Read more.

Background: Tropaeolum pentaphyllum Lam. tubers (Tropaeolaceae) are known and used as a condiment and for the treatment of skin infections in Southern Brazil. However, its activity and composition has not yet been investigated. Thus, different extracts and the essential oil from the tubers were tested against a range of microorganisms. The most active extracts were submitted to chromatographic analysis. Methods: Hydroalcoholic extract (70%), fractions of it, and the essential oil from the tubers were tested against several bacteria, yeasts and molds, furnishing the corresponding inhibitory, bactericidal and fungicidal minimal concentration values. The most active extracts were submitted to GC-MS investigation. Results: The strongest effects against different strains of microorganisms, such as Gram-positive and negative bacteria, Candida spp. and dermatophytes were observed for the essential oil and the chloroform fraction, with minimal inhibitory concentrations (MICs) well below 200 µg/mL. GC-MS analysis revealed that the major essential oil constituent is benzyl isothiocyanate (BITC), while the chloroform fraction is constituted of BITC, amides, sulfur, fatty acids and its esters, all compounds that may be related to the demonstrated activity. Conclusions: Overall, the results support the popular use of the plant for the treatment of skin infections, and revealed the main active compounds. Full article

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Open AccessArticle

Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

by Wenxia Gong, Yuzhi Zhou, Xiao Li, Xiaoxia Gao, Junsheng Tian, Xuemei Qin and Guanhua Du

Molecules 2016, 21(5), 549; https://doi.org/10.3390/molecules21050549 - 26 Apr 2016

Cited by 39 | Viewed by 7044 | Correction

Abstract

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the [...] Read more.

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC₅₀ values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects. Full article

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Repellent Activity of the Essential Oil from the Heartwood of Pilgerodendron uviferum (D. Don) Florin against Aegorhinus superciliosus (Coleoptera: Curculionidae)

by Javier Espinoza, Alejandro Urzúa, Jocelyne Tampe, Leonardo Parra and Andrés Quiroz

Molecules 2016, 21(4), 533; https://doi.org/10.3390/molecules21040533 - 22 Apr 2016

Cited by 11 | Viewed by 5667

Abstract

The weevil Aegorhinus superciliosus Guérin (Coleoptera: Curculionidae), which is endemic to Central-Southern Chile and Argentina, is one of the major berry pests in Chile and the most important pest in the La Araucanía Region (38°44′9″S, 72°35′25″W). Due to the poor effectiveness and problems [...] Read more.

The weevil Aegorhinus superciliosus Guérin (Coleoptera: Curculionidae), which is endemic to Central-Southern Chile and Argentina, is one of the major berry pests in Chile and the most important pest in the La Araucanía Region (38°44′9″S, 72°35′25″W). Due to the poor effectiveness and problems surrounding the implementation of the traditional control methods using organophosphate and carbamate insecticides, new strategies for controlling this pest are needed. In this communication, we evaluated the behavioral responses of male and female A. superciliosus to volatile compounds released from the essential oil (EO) obtained from the heartwood of Pilgerodendron uviferum (D. Don) Florin using olfactometric bioassays. The composition of the EO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). According to these analyses, δ-cadinol (24.16%), cubenol (22.64%), 15-copaenol (15.46%) and δ-cadinene (10.81%) were the principal components of the EO. The Pilgerodendron uviferum EO, which is almost exclusively composed of sesquiterpenes (99.5%), exhibited a repellent effect against A. superciliosus adults, regardless of the sex or concentration used (56.6 mg/cm³ and 1.58 × 10⁻² mg/cm³). The EO has low volatility and greater persistence than the EOs composed of monoterpenes and is considered a good model in the search for raspberry weevil repellents. Full article

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Open AccessArticle

Quality Control of Gamma Irradiated Dwarf Mallow (Malva neglecta Wallr.) Based on Color, Organic Acids, Total Phenolics and Antioxidant Parameters

by José Pinela, Lillian Barros, Amilcar L. Antonio, Ana Maria Carvalho, M. Beatriz P. P. Oliveira and Isabel C. F. R. Ferreira

Molecules 2016, 21(4), 467; https://doi.org/10.3390/molecules21040467 - 8 Apr 2016

Cited by 11 | Viewed by 7198

Abstract

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to [...] Read more.

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to a photodiode array (PDA) detector. Total phenolics and flavonoids were measured by the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The antioxidant activity was evaluated based on the DPPH^• scavenging activity, reducing power, β-carotene bleaching inhibition and thiobarbituric acid reactive substances (TBARS) formation inhibition. Analyses were performed in the non-irradiated and irradiated plant material, as well as in decoctions obtained from the same samples. The total amounts of organic acids and phenolics recorded in decocted extracts were always higher than those found in the plant material or hydromethanolic extracts, respectively. The DPPH^• scavenging activity and reducing power were also higher in decocted extracts. The assayed irradiation doses affected differently the organic acids profile. The levels of total phenolics and flavonoids were lower in the hydromethanolic extracts prepared from samples irradiated at 1 kGy (dose that induced color changes) and in decocted extracts prepared from those irradiated at 8 kGy. The last samples also showed a lower antioxidant activity. In turn, irradiation at 5 kGy favored the amounts of total phenolics and flavonoids. Overall, this study contributes to the understanding of the effects of irradiation in indicators of dwarf mallow quality, and highlighted the decoctions for its antioxidant properties. Full article

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NMR Study on the Inclusion Complexes of β-Cyclodextrin with Isoflavones

by Rui Zhao, Corine Sandström, Haiyang Zhang and Tianwei Tan

Molecules 2016, 21(4), 372; https://doi.org/10.3390/molecules21040372 - 28 Mar 2016

Cited by 51 | Viewed by 8328

Abstract

The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D₂O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD [...] Read more.

The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D₂O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD cavity with different orientations. For the β-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of daidzin entering the CD cavity from the wide rim. The inclusion complexes determined by NMR were constructed using molecular docking. Furthermore, the mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid components present in Radix puerariae, was analyzed by diffusion-ordered spectroscopy (DOSY) alone and upon addition of β-CD in order to mimic chromatographic conditions and compare their binding affinities. Full article

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Open AccessArticle

New Anti-HBV C-Boivinopyranosyl Flavones from Alternanthera philoxeroides

by Bin Li, Qing-Lan Guo, Ying Tian, Shi-Jun Liu, Qiong Wang, Li Chen and Jun-Xing Dong

Molecules 2016, 21(3), 336; https://doi.org/10.3390/molecules21030336 - 14 Mar 2016

Cited by 14 | Viewed by 5389

Abstract

C-boivinopyranosyl flavones have rarely been isolated from nature. In the search for anti-HBV (hepatitis b virus) constituents of Alternanthera philoxeroides, two new compounds, luteolin-6-C-β-d-boivinopyranosyl-3′-O-β-d-glucopyranoside (1) and chrysoeriol-6-C-β-d-boivinopyranosyl-4′-O-β- [...] Read more.

C-boivinopyranosyl flavones have rarely been isolated from nature. In the search for anti-HBV (hepatitis b virus) constituents of Alternanthera philoxeroides, two new compounds, luteolin-6-C-β-d-boivinopyranosyl-3′-O-β-d-glucopyranoside (1) and chrysoeriol-6-C-β-d-boivinopyranosyl-4′-O-β-d-glucopyranoside (2), along with three known C-boivinopyranosyl flavones (compounds 3–5) were isolated. Their structures were determined by spectroscopic analyses including 1D and 2D NMR, HR-ESI-MS, IR spectra. Compounds 1, 2 and 3 showed significant anti-HBV activities through specifically inhibiting the secretion of HBsAg in HepG2.2.15. Full article

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New Cerebroside and Nucleoside Derivatives from a Red Sea Strain of the Marine Cyanobacterium Moorea producens

by Diaa T.A. Youssef, Sabrin R.M. Ibrahim, Lamiaa A. Shaala, Gamal A. Mohamed and Zainy M. Banjar

Molecules 2016, 21(3), 324; https://doi.org/10.3390/molecules21030324 - 9 Mar 2016

Cited by 15 | Viewed by 5699

Abstract

In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), [...] Read more.

In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1–5 showed variable cytotoxic activity against three cancer cell lines. Full article

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Liquid Chromatography with Tandem Mass Spectrometry: A Sensitive Method for the Determination of Dehydrodiisoeugenol in Rat Cerebral Nuclei

by You-Bo Zhang, Xin-Bao Yang, Xiu-Wei Yang, Wei Xu, Fei Li and Frank J. Gonzezal

Molecules 2016, 21(3), 321; https://doi.org/10.3390/molecules21030321 - 9 Mar 2016

Cited by 15 | Viewed by 5316

Abstract

A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C₁₈ column with methanol–water containing 0.1% formic [...] Read more.

A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C₁₈ column with methanol–water containing 0.1% formic acid (81:19, v/v) as a mobile phase. Detection of DDIE was performed on a positive electrospray ionization source using a triple quadrupole mass spectrometer. DDIE and daidzein were monitored at m/z 327.2→188.0 and m/z 255.0→199.2, respectively, in multiple reaction monitoring mode. This method enabled quantification of DDIE in various brain areas, including, cortex, hippocampus, striatum, hypothalamus, cerebellum and brainstem, with high specificity, precision, accuracy, and recovery. The data herein demonstrate that our new LC-MS/MS method is highly sensitive and suitable for monitoring cerebral nuclei distribution of DDIE. Full article

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Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans

by Dominique Heymann, Carmen Ruiz-Velasco, Julie Chesneau, Jacqueline Ratiskol, Corinne Sinquin and Sylvia Colliec-Jouault

Molecules 2016, 21(3), 309; https://doi.org/10.3390/molecules21030309 - 4 Mar 2016

Cited by 24 | Viewed by 5932

Abstract

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were [...] Read more.

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies. Full article

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Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits

by Kun Liu, Wei Wang, Bing-Hua Guo, Hua Gao, Yang Liu, Xiao-Hong Liu, Hui-Li Yao and Kun Cheng

Molecules 2016, 21(3), 302; https://doi.org/10.3390/molecules21030302 - 2 Mar 2016

Cited by 41 | Viewed by 7713

Abstract

Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. [...] Read more.

Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC₅₀ value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia. Full article

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Optimization of Microwave-Assisted Extraction Conditions for Five Major Bioactive Compounds from Flos Sophorae Immaturus (Cultivars of Sophora japonica L.) Using Response Surface Methodology

by Jin-Liang Liu, Long-Yun Li and Guang-Hua He

Molecules 2016, 21(3), 296; https://doi.org/10.3390/molecules21030296 - 2 Mar 2016

Cited by 46 | Viewed by 8499

Abstract

Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design [...] Read more.

Microwave-assisted extraction was applied to extract rutin; quercetin; genistein; kaempferol; and isorhamnetin from Flos Sophorae Immaturus. Six independent variables; namely; solvent type; particle size; extraction frequency; liquid-to-solid ratio; microwave power; and extraction time were examined. Response surface methodology using a central composite design was employed to optimize experimental conditions (liquid-to-solid ratio; microwave power; and extraction time) based on the results of single factor tests to extract the five major components in Flos Sophorae Immaturus. Experimental data were fitted to a second-order polynomial equation using multiple regression analysis. Data were also analyzed using appropriate statistical methods. Optimal extraction conditions were as follows: extraction solvent; 100% methanol; particle size; 100 mesh; extraction frequency; 1; liquid-to-solid ratio; 50:1; microwave power; 287 W; and extraction time; 80 s. A rapid and sensitive ultra-high performance liquid chromatography method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (EIS-Q-TOF MS/MS) was developed and validated for the simultaneous determination of rutin; quercetin; genistein; kaempferol; and isorhamnetin in Flos Sophorae Immaturus. Chromatographic separation was accomplished on a Kinetex C₁₈ column (100 mm × 2.1 mm; 2.6 μm) at 40 °C within 5 min. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile (71:29; v/v). Isocratic elution was carried out at a flow rate of 0.35 mL/min. The constituents of Flos Sophorae Immaturus were simultaneously identified by EIS-Q-TOF MS/MS in multiple reaction monitoring mode. During quantitative analysis; all of the calibration curves showed good linear relationships (R² > 0.999) within the tested ranges; and mean recoveries ranged from 96.0216% to 101.0601%. The precision determined through intra- and inter-day studies showed an RSD% of <2.833%. These results demonstrate that the developed method is accurate and effective and could be readily utilized for the comprehensive quality control of Flos Sophorae Immaturus. Full article

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Sesquiterpenoids from Chinese Agarwood Induced by Artificial Holing

by Wei Li, Ge Liao, Wen-Hua Dong, Fan-Dong Kong, Pei Wang, Hao Wang, Wen-Li Mei and Hao-Fu Dai

Molecules 2016, 21(3), 274; https://doi.org/10.3390/molecules21030274 - 26 Feb 2016

Cited by 39 | Viewed by 5943

Abstract

Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) [...] Read more.

Two new sesquiterpenoids, 3-oxo-7-hydroxylholosericin A (1) and 1,5;8,12-diepoxy-guaia-12-one (2), together with seven known sesquiterpenoids 3–9, were isolated from Chinese agarwood induced by artificial holing originating from Aquilaria sinensis (Lour.) Gilg. Their structures were identified by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. The absolute configuration of compound 1 was determined by comparison of its measured CD curve with that of calculated data for 1 and ent-1. The NMR data of 3 were reported in this study for the first time. Compounds 1, 2, 4–6, together with the EtOAc extract showed moderate inhibitory activities against acetylcholinesterase, and compounds 4–6, 8 exhibited antibacterial activities against Staphylococcus aureus or Ralstonia solanacearum. Full article

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Biochemical Characteristics of Three Laccase Isoforms from the Basidiomycete Pleurotus nebrodensis

by Xianghe Yuan, Guoting Tian, Yongchang Zhao, Liyan Zhao, Hexiang Wang and Tzi Bun Ng

Molecules 2016, 21(2), 203; https://doi.org/10.3390/molecules21020203 - 6 Feb 2016

Cited by 34 | Viewed by 5971

Abstract

The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified [...] Read more.

The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified laccases were estimated to be 68, 64 and 51 kDa, respectively. The isoenzymes demonstrated the same optimum pH at 3.0 but slightly different temperature optima: 50–60 °C for Lac1 and Lac3 and 60 °C for Lac2. Lac2 was always more stable than the other two isoforms and exposure to 50 °C for 120 min caused 30% loss in activity. Lac2 was relatively less stable than the other two isoforms when exposed to the pH range of 3.0–8.0 for 24 h, but inactivation only occurred initially, with around 70% residual activity being maintained during the whole process. Oxidative ability towards aromatic compounds varied substantially among the isoforms and each of them displayed preference toward some substrates. Kinetic constants (K_m, K_cat) were determined by using a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay, with Lac3 showing the best affinity and Lac2 displaying the highest catalytic efficiency. Amino acid sequences from peptides derived from digestion of isoenzymes showed great consistency with laccases in the databases. Full article

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Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E

by Lorena M. C. Cursino, Nerilson M. Lima, Renato Murillo, Cecilia V. Nunez, Irmgard Merfort and Matjaz Humar

Molecules 2016, 21(2), 192; https://doi.org/10.3390/molecules21020192 - 6 Feb 2016

Cited by 9 | Viewed by 5852

Abstract

Preparations of Deguelia duckeana, known in Brazil as timbó, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4’-trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine ( [...] Read more.

Preparations of Deguelia duckeana, known in Brazil as timbó, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4’-trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine (3), 4-hydroxylonchocarpine (4), 4-methoxylonchocarpine (5), 5-hydroxy-4’,7-dimethoxy-6-prenylflavanone (6), 4’-hydroxyisolonchocarpine (7), 4’-methoxyisolonchocarpine (8), 3’,4’,7-trimethoxyflavone (9), 3’,4’-methylenedioxy-7-methoxyflavone (10), and 2,2-dimethyl-chromone-5,4’-hydroxy-5’-methoxyflavone (11). Except for 1, 3, and 4 all of these flavonoids have been described for the first time in D. duckeana and the flavanone 6 for the first time in nature. Compounds 2, 3, 4, 7, 9, and 10 were studied for their potential to induce cell death in neuronal SK-N-SH cells. Only the chalcone 4 and the flavanone 7 significantly induced lactate dehydrogenase (LDH) release, which was accompanied by activation of caspase-3 and impairment of energy homeostasis in the MTT assay and may explain the killing effect on fish. Interestingly, the flavone 10 reduced cell metabolism in the MTT assay without inducing cytotoxicity in the LDH assay. Furthermore, the flavonoids 2, 3, 4, 7, and 10 induced phosphorylation of the AMP-activated protein kinase (AMPK) and the eukaryotic elongation factor 2 (eEF2). The initiation factor eIF4E was dephosphorylated in the presence of these compounds. The initiation factor eIF2alpha was not affected. Further studies are needed to elucidate the importance of the observed effects on protein synthesis and potential therapeutic perspectives. Full article

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Nutritional and Biochemical Profiling of Leucopaxillus candidus (Bres.) Singer Wild Mushroom

by Vanessa Vieira, Lillian Barros, Anabela Martins and Isabel C. F. R. Ferreira

Molecules 2016, 21(1), 99; https://doi.org/10.3390/molecules21010099 - 15 Jan 2016

Cited by 8 | Viewed by 5714

Abstract

The wild mushroom Leucopaxillus candidus (Bres.) Singer was studied for the first time to obtain information about its chemical composition, nutritional value and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. [...] Read more.

The wild mushroom Leucopaxillus candidus (Bres.) Singer was studied for the first time to obtain information about its chemical composition, nutritional value and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. candidus methanolic extract was tested regarding antioxidant potential (reducing power, radical scavenging activity and lipid peroxidation inhibition). L. candidus was shown to be an interesting species in terms of nutritional value, with high content in proteins and carbohydrates, but low fat levels, with the prevalence of polyunsaturated fatty acids. Mannitol was the most abundant free sugar and β-tocopherol was the main tocopherol isoform. Other compounds detected were oxalic and fumaric acids, p-hydroxybenzoic and cinnamic acids. The methanolic extract revealed antioxidant activity and did not show hepatoxicity in porcine liver primary cells. The present study provides new information about L. candidus. Full article

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A New Bioactive Metabolite Isolated from the Red Sea Marine Sponge Hyrtios erectus

by Sameh S. Elhady, Ali M. El-Halawany, Abdulrahman M. Alahdal, Hashim A. Hassanean and Safwat A. Ahmed

Molecules 2016, 21(1), 82; https://doi.org/10.3390/molecules21010082 - 15 Jan 2016

Cited by 30 | Viewed by 7336

Abstract

Chemical investigation of the lipophilic fraction of Hyrtios erectus, a Red Sea sponge, yielded a new pentacyclic nitrogen-containing scalarane; 24-methoxypetrosaspongia C (1), together with the previously reported scalaranes sesterstatin 3 (2), 12-deacetyl-12-epi-scalaradial (3) and [...] Read more.

Chemical investigation of the lipophilic fraction of Hyrtios erectus, a Red Sea sponge, yielded a new pentacyclic nitrogen-containing scalarane; 24-methoxypetrosaspongia C (1), together with the previously reported scalaranes sesterstatin 3 (2), 12-deacetyl-12-epi-scalaradial (3) and 12-deacetyl-12,18-di-epi-scalaradial (4). The compounds were identified using HRESIMS, 1D and 2D NMR experiments. The isolated compounds showed growth inhibitory activity against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116) and breast adenocarcinoma cells (MCF-7). Full article

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Open AccessArticle

Terpenoids from the Marine-Derived Fungus Aspergillus fumigatus YK-7

by Yu Wang, Da-Hong Li, Zhan-Lin Li, Yan-Jun Sun, Hui-Ming Hua, Tao Liu and Jiao Bai

Molecules 2016, 21(1), 31; https://doi.org/10.3390/molecules21010031 - 28 Dec 2015

Cited by 23 | Viewed by 6282

Abstract

Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods [...] Read more.

Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC₅₀ value of 4.2 μM. Full article

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Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40

by Yong-Qi Tian, Xiu-Ping Lin, Zhen Wang, Xue-Feng Zhou, Xiao-Chu Qin, Kumaravel Kaliyaperumal, Tian-Yu Zhang, Zheng-Chao Tu and Yonghong Liu

Molecules 2016, 21(1), 34; https://doi.org/10.3390/molecules21010034 - 26 Dec 2015

Cited by 48 | Viewed by 8217

Abstract

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds ( [...] Read more.

Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC₅₀ values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC₅₀ value of 3.5 ± 1.3 μM. Full article

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Open AccessCommunication

Guignardones P–S, New Meroterpenoids from the Endophytic Fungus Guignardia mangiferae A348 Derived from the Medicinal Plant Smilax glabra

by Zhang-Hua Sun, Fa-Liang Liang, Wen Wu, Yu-Chan Chen, Qing-Ling Pan, Hao-Hua Li, Wei Ye, Hong-Xin Liu, Sai-Ni Li, Guo-Hui Tan and Wei-Min Zhang

Molecules 2015, 20(12), 22900-22907; https://doi.org/10.3390/molecules201219890 - 21 Dec 2015

Cited by 29 | Viewed by 6541

Abstract

Four new meroterpenoids, guignardones P–S (1–4), and three known analogues (5–7) were isolated from the endophytic fungal strain Guignardia mangiferae A348. Their structures were elucidated on the basis of spectroscopic analysis and single crystal X-ray [...] Read more.

Four new meroterpenoids, guignardones P–S (1–4), and three known analogues (5–7) were isolated from the endophytic fungal strain Guignardia mangiferae A348. Their structures were elucidated on the basis of spectroscopic analysis and single crystal X-ray diffraction. All the isolated compounds were evaluated for their inhibitory effects on SF-268, MCF-7, and NCI-H460 human cancer cell lines. Compounds 2 and 4 exhibited weak inhibitions of cell proliferation against MCF-7 cell line. Full article

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Open AccessCommunication

Fatty Acid Profile and Biological Activities of Linseed and Rapeseed Oils

by Anna Lewinska, Jacek Zebrowski, Magdalena Duda, Anna Gorka and Maciej Wnuk

Molecules 2015, 20(12), 22872-22880; https://doi.org/10.3390/molecules201219887 - 21 Dec 2015

Cited by 70 | Viewed by 9464

Abstract

It has been postulated that fatty acids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected [...] Read more.

It has been postulated that fatty acids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected edible oils—linseed (LO) and rapeseed (RO) oils—were tested in vitro on fibroblast cells. The fatty acid profile of the oils was determined using gas chromatography and FTIR spectroscopy. LO was found to be rich in α-linolenic acid (ALA), whereas oleic acid was the most abundant species in RO. Fatty acids were taken up by the cells and promoted cell proliferation. No oxidative stress-mediated cytotoxic or genotoxic effects were observed after oil stimulation. Oils ameliorated the process of wound healing as judged by improved migration of fibroblasts to the wounding area. As ALA-rich LO exhibited the most potent wound healing activity, ALA may be considered a candidate for promoting the observed effect. Full article

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Open AccessArticle

Bioactive Properties of Tabebuia impetiginosa-Based Phytopreparations and Phytoformulations: A Comparison between Extracts and Dietary Supplements

by Tânia C. S. P. Pires, Maria Inês Dias, Ricardo C. Calhelha, Ana Maria Carvalho, Maria-João R. P. Queiroz, Lillian Barros and Isabel C. F. R. Ferreira

Molecules 2015, 20(12), 22863-22871; https://doi.org/10.3390/molecules201219885 - 21 Dec 2015

Cited by 18 | Viewed by 8906

Abstract

Tabebuia impetiginosa (Mart. ex DC.) Standl. has been used in traditional medicine for many centuries, being nowadays marketed as dried plant material (inner bark) for infusions, pills, and syrups. The main objective of the present work was to validate its popular use through [...] Read more.

Tabebuia impetiginosa (Mart. ex DC.) Standl. has been used in traditional medicine for many centuries, being nowadays marketed as dried plant material (inner bark) for infusions, pills, and syrups. The main objective of the present work was to validate its popular use through the bioactivity evaluation of the inner bark (methanolic extract and infusion) and of two different formulations (pills and syrup) also based on the same plant-material. The antioxidant activity was evaluated by in vitro assays testing free radical scavenging activity, reducing power and inhibition of lipid peroxidation in brain homogenates. The cytotoxicity was determined in four human tumor cell lines (MCF-7, NCI-H460, HeLa and HepG2, and also in non-tumor cells (porcine liver primary cells, PLP2)). Furthermore, the sample was chemically characterized regarding free sugars, organic acids, fatty acids, and tocopherols. Syrup and methanolic extract showed the highest antioxidant activity, related to their highest amount of phenolics and flavonoids. Methanolic extract was the only sample showing cytotoxic effects on the tested human tumor cell lines, but none of the samples showed toxicity in PLP2. Glucose and oxalic acid were, respectively, the most abundant sugar and organic acid in the sample. Unsaturated predominated over the saturated fatty acids, due to oleic, linoleic, and linolenic acids expression. α- and γ-Tocopherols were also identified and quantified. Overall, T. impetiginosa might be used in different phytoformulations, taking advantage of its interesting bioactive properties and chemical composition. Full article

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Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

by Opeyemi J. Olatunji, Hongxia Chen and Yifeng Zhou

Molecules 2015, 20(12), 22553-22564; https://doi.org/10.3390/molecules201219867 - 16 Dec 2015

Cited by 23 | Viewed by 6870

Abstract

The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior [...] Read more.

The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers. Full article

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Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence

by Ela Alcántara-Flores, Alicia Enriqueta Brechú-Franco, Patricia García-López, Leticia Rocha-Zavaleta, Rebeca López-Marure and Mariano Martínez-Vázquez

Molecules 2015, 20(12), 21125-21137; https://doi.org/10.3390/molecules201219757 - 27 Nov 2015

Cited by 14 | Viewed by 7601

Abstract

Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. [...] Read more.

Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. The cell cycle was studied by flow cytometry. Apoptosis was evaluated by Annexin-V-Fluos, and Hoechst 33342 dye staining. Cell senescence was evaluated by proliferation tests, and staining for SA-β-galactosidase. Senescence-related proteins (PCNA, p21, and p27) were analyzed by Western blotting. Potential toxicity of argentatin B was evaluated in CD-1 mice. Its effect on tumor growth was tested in a HCT-15 and PC-3 xenograft model. Argentatin B induced an increment of cells in sub G1, but did not produce apoptosis. Proliferation of both cell lines was inhibited by argentatin B. Forty-three percent HCT-15, and 66% PC-3 cells showed positive SA-β-galactosidase staining. The expression of PCNA was decreased, p21 expression was increased in both cell lines, but p27 expression increased only in PC-3 cells after treatment. Administration of argentatin B to healthy mice did not produce treatment-associated pathologies. However, it restricted the growth of HCT-15 and PC-3 tumors. These results indicate that treatment with argentatin B induces cell senescence. Full article

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Open AccessArticle

Pyranocoumarins from Root Extracts of Peucedanum praeruptorum Dunn with Multidrug Resistance Reversal and Anti-Inflammatory Activities

by Jun Lee, You Jin Lee, Jinhee Kim and Ok-Sun Bang

Molecules 2015, 20(12), 20967-20978; https://doi.org/10.3390/molecules201219738 - 25 Nov 2015

Cited by 48 | Viewed by 7025

Abstract

In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3′S,4′S)-3′-angeloyl-4′-tigloylkhellactone (1) along with 12 pyranocoumarins (2–13), two furanocoumarins (14, 15), and a polyacetylene [...] Read more.

In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3′S,4′S)-3′-angeloyl-4′-tigloylkhellactone (1) along with 12 pyranocoumarins (2–13), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). The multidrug-resistance (MDR) reversal and anti-inflammatory effects of all the isolated compounds were evaluated in human sarcoma MES-SA/Dx5 and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among the 16 tested compounds, two (2 and 16) downregulated nitric oxide (NO) production and five (1, 7, 8, 11, and 13) inhibited the efflux of drugs by MDR protein, indicating the reversal of MDR. Therefore, these compounds may be potential candidates for the development of effective agents against MDR forms of cancer. Full article

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Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

by Yihan Hu, Xiaoxu Bi, Pu Zhao, Huachuan Zheng and Xueshi Huang

Molecules 2015, 20(11), 20312-20319; https://doi.org/10.3390/molecules201119699 - 12 Nov 2015

Cited by 12 | Viewed by 5877

Abstract

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, [...] Read more.

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp² carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5. Full article

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Open AccessArticle

Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage

by Wen-Li Hsu, Jian-He Lu, Mami Noda, Ching-Ying Wu, Jia-dai Liu, Manabu Sakakibara, Ming-Hsien Tsai, Hsin-Su Yu, Ming-Wei Lin, Yaw-Bin Huang, Shian-Jang Yan and Tohru Yoshioka

Molecules 2015, 20(11), 20297-20311; https://doi.org/10.3390/molecules201119693 - 12 Nov 2015

Cited by 21 | Viewed by 10522

Abstract

Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca²⁺ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases [...] Read more.

Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca²⁺ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging. Full article

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Open AccessCorrection

Correction: Wang L.K., et al. Two New Lanostane Triterpenoids from the Branches and Leaves of Polyalthia oblique. Molecules 2014, 19, 7621–7628

by Liu-Kai Wang, Cai-Juan Zheng, Xiao-Bao Li, Guang-Ying Chen, Chang-Ri Han, Wen-Hao Chen and Xiao-Ping Song

Molecules 2015, 20(11), 20268; https://doi.org/10.3390/molecules201119690 - 11 Nov 2015

Cited by 1 | Viewed by 4568

Abstract

The authors wish to make the following correction to their paper [1], published recently in Molecules. [...] Full article

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Open AccessArticle

Antihypertensive Effects of Artemisia scoparia Waldst in Spontaneously Hypertensive Rats and Identification of Angiotensin I Converting Enzyme Inhibitors

by Jeong-Yong Cho, Kyung-Hee Park, Do Young Hwang, Saoraya Chanmuang, Lily Jaiswal, Yang-Kyun Park, Sun-Young Park, So-Young Kim, Haeng-Ran Kim, Jae-Hak Moon and Kyung-Sik Ham

Molecules 2015, 20(11), 19789-19804; https://doi.org/10.3390/molecules201119657 - 3 Nov 2015

Cited by 29 | Viewed by 8044

Abstract

We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic [...] Read more.

We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4′-O-β-D-glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data. Full article

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Open AccessArticle

Cytotoxicity of Triterpenes from Green Walnut Husks of Juglans mandshurica Maxim in HepG-2 Cancer Cells

by Yuanyuan Zhou, Bingyou Yang, Zhaoxi Liu, Yanqiu Jiang, Yuxin Liu, Lei Fu, Xiaoli Wang and Haixue Kuang

Molecules 2015, 20(10), 19252-19262; https://doi.org/10.3390/molecules201019252 - 22 Oct 2015

Cited by 29 | Viewed by 6854

Abstract

Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans [...] Read more.

Among the classes of identified natural products, triterpenoids, one of the largest families, have been studied extensively for their diverse structures and variety of biological activities, including antitumor effects. In the present study, a phytochemical study of the green walnut husks of Juglans mandshurica Maxim led to the isolation of a new dammarane triterpene, 12β, 20(R), 24(R)-trihydroxydammar-25-en-3-one (6), together with sixteen known compounds, chiefly from chloroform and ethyl acetate extracts. According to their structural characteristics, these compounds were divided into dammarane-type, oleanane- and ursane-type. Dammarane-type triterpenoids were isolated for the first time from the Juglans genus. As part of our continuing search for biologically active compounds from this plant, all of these compounds were also evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by the MTT assay. The results were shown that 20(S)-protopanaxadiol, 2α,3β,23-trihydroxyolean-12-en-28-oic acid and 2α,3β,23-trihydroxyurs-12-en-28-oic acid exhibited better cytotoxicity in vitro with IC₅₀ values of 10.32 ± 1.13, 16.13 ± 3.83, 15.97 ± 2.47 μM, respectively. Preliminary structure-activity relationships for these compounds were discussed. Full article

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Open AccessArticle

Antioxidant Properties of Essential Oil Extracted from Pinus morrisonicola Hay Needles by Supercritical Fluid and Identification of Possible Active Compounds by GC/MS

by Ming-Ching Cheng, Wen-Hua Chang, Chih-Wei Chen, Wen-Wing Li, Chin-Yin Tseng and Tuzz-Ying Song

Molecules 2015, 20(10), 19051-19065; https://doi.org/10.3390/molecules201019051 - 20 Oct 2015

Cited by 16 | Viewed by 7959

Abstract

Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the [...] Read more.

Pine (Pinus morrisonicola Hay, PM) needles have been used as folk medicine for their antihypertension and lipid-lowering effects. As supercritical fluid extraction (SFE) is considered an ideal technique for the extraction of essential oil from plant materials, the present work investigated the optimal SFE conditions and the protective effects of different resulting fractions of PM needles on lipid peroxidation and foam cell production in macrophages. Nine PM needle extracts (PME1–9) were obtained in 1%–4% yields using different SFE conditions, of which PME1 had the lowest yield (1.1%) and PME3 the highest (3.9%). PME3 exhibited lower cytotoxic effects and stronger inhibition of lipid peroxidation and formation of foam cell in RAW 264.7 macrophages than those of other PME extracts. PME3-1 purified from PME3 by column and thin layer chromatography inhibited LDL oxidation more effectively than did PME3 in a cell-free system oxidized by Cu²⁺. PME3-1 dose-dependently (25–100 μg/mL) decreased conjugated diene levels and foam cell formation induced by ox-LDL. GC/MS analyses revealed that 1-docosene, neophytadiene, and methyl abietate were increased 5.2-, 1.7- and 4.3-fold in PME3-1 relative to PME3. A new hydrocarbon compound, cedrane-8,13-diol, was identified in PME3-1. Overall, the present study demonstrates the optimal extraction conditions of SFE of PM and identifies the most potent antioxidant fractions and possible active compounds in PM. Full article

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Open AccessArticle

Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells

by Filipa S. Reis, Raquel T. Lima, Patricia Morales, Isabel C. F. R. Ferreira and M. Helena Vasconcelos

Molecules 2015, 20(10), 17872-17882; https://doi.org/10.3390/molecules201017872 - 29 Sep 2015

Cited by 40 | Viewed by 8497

Abstract

Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was [...] Read more.

Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement. Full article

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Open AccessArticle

Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens

by Li-Na Huo, Wei Wang, Chun-Yu Zhang, Hai-Bo Shi, Yang Liu, Xiao-Hong Liu, Bing-Hua Guo, Dong-Mei Zhao and Hua Gao

Molecules 2015, 20(10), 17848-17859; https://doi.org/10.3390/molecules201017848 - 25 Sep 2015

Cited by 55 | Viewed by 9523

Abstract

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia [...] Read more.

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia. Full article

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Open AccessArticle

Insecticidal Constituents and Activity of Alkaloids from Cynanchum mongolicum

by Yang Ge, Pingping Liu, Rui Yang, Liu Zhang, Hongxing Chen, Ibrahima Camara, Yiqing Liu and Wangpeng Shi

Molecules 2015, 20(9), 17483-17492; https://doi.org/10.3390/molecules200917483 - 21 Sep 2015

Cited by 33 | Viewed by 6041

Abstract

Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they [...] Read more.

Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they were less active against Spodoptera litura than total alkaloids. The contact toxicity from these alkaloids against the aphid Lipaphis erysimi was significant, as the 24 h-LC₅₀ values of alkaloids I, II, III and total alkaloids were 292.48, 367.21, 487.791 and 163.52 mg/L, respectively. The development disruption of S. litura larvae was tested, the pupation and emergence rates of S. litura decreased and the acute mortality of S. litura increased significantly by day 3 after being injected in their body cavity with 10–40 mg/L of total alkaloid. The ecdysone titer of treated S. litura larvae and prepupae declined with increasing alkaloid concentration. The alkaloids of Cynanchum mongolicum are potential insect growth inhibitors. Full article

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Open AccessArticle

Studies on Cytotoxic Activity against HepG-2 Cells of Naphthoquinones from Green Walnut Husks of Juglans mandshurica Maxim

by Yuanyuan Zhou, Bingyou Yang, Yanqiu Jiang, Zhaoxi Liu, Yuxin Liu, Xiaoli Wang and Haixue Kuang

Molecules 2015, 20(9), 15572-15588; https://doi.org/10.3390/molecules200915572 - 26 Aug 2015

Cited by 66 | Viewed by 6792

Abstract

Twenty-seven naphthoquinones and their derivatives, including four new naphthalenyl glucosides and twenty-three known compounds, were isolated from green walnut husks, which came from Juglans mandshurica Maxim. The structures of four new naphthalenyl glucosides were elucidated based on extensive spectroscopic analyses. All of these [...] Read more.

Twenty-seven naphthoquinones and their derivatives, including four new naphthalenyl glucosides and twenty-three known compounds, were isolated from green walnut husks, which came from Juglans mandshurica Maxim. The structures of four new naphthalenyl glucosides were elucidated based on extensive spectroscopic analyses. All of these compounds were evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by MTT [3-(4,5-dimethylthiazo l-2-yl)-2,5 diphenyl tetrazolium bromide] assay. The results were shown that most naphthoquinones in an aglycone form exhibited better cytotoxicity in vitro than naphthalenyl glucosides with IC₅₀ values in the range of 7.33–88.23 μM. Meanwhile, preliminary structure-activity relationships for these compounds were discussed. Full article

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Open AccessArticle

α-Glucosidase Inhibitors from Vauquelinia corymbosa

by Laura Flores-Bocanegra, Araceli Pérez-Vásquez, Mariana Torres-Piedra, Robert Bye, Edelmira Linares and Rachel Mata

Molecules 2015, 20(8), 15330-15342; https://doi.org/10.3390/molecules200815330 - 21 Aug 2015

Cited by 41 | Viewed by 7527

Abstract

The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC₅₀) of 28.6 [...] Read more.

The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC₅₀) of 28.6 μg/mL. Bioassay-guided fractionation of the extract led to the isolation of several compounds, including one cyanogenic glycoside [prunasin (1)], five flavonoids [(−)-epi-catechin (2), hyperoside (3), isoquercetin (4), quercitrin (5) and quercetin-3-O-(6′′-benzoyl)-β-galactoside (6)] and two simple aromatic compounds [picein (7) and methylarbutin (8)]. The most active compound was 6 with IC₅₀ values of 30 μM in the case of yeast α-glucosidase, and 437 μM in the case of the mammalian enzyme. According to the kinetic analyses performed with rat and yeast enzymes, this compound behaved as mixed-type inhibitor; the calculated inhibition constants (K_i) were 212 and 50 μM, respectively. Molecular docking analyses with yeast and mammalian α-glucosidases revealed that compound 6 bind differently to these enzymes. Altogether, the results of this work suggest that preparations of V. corymbosa might delay glucose absorption in vivo. Full article

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Open AccessArticle

Salvia miltiorrhiza Induces Tonic Contraction of the Lower Esophageal Sphincter in Rats via Activation of Extracellular Ca²⁺ Influx

by Ching-Chung Tsai, Li-Ching Chang, Shih-Che Huang, Shu-Leei Tey, Wen-Li Hsu, Yu-Tsun Su, Ching-Wen Liu and Tong-Rong Tsai

Molecules 2015, 20(8), 14504-14521; https://doi.org/10.3390/molecules200814504 - 11 Aug 2015

Cited by 8 | Viewed by 6299

Abstract

Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia [...] Read more.

Up to 40% of patients with gastroesophageal reflux disease (GERD) suffer from proton pump inhibitor refractory GERD but clinically the medications to strengthen the lower esophageal sphincter (LES) to avoid irritating reflux are few in number. This study aimed to examine whether Salvia miltiorrhiza (SM) extracts induce tonic contraction of rat LES ex vivo and elucidate the underlying mechanisms. To investigate the mechanism underlying the SM extract-induced contractile effects, rats were pretreated with atropine (a muscarinic receptor antagonist), tetrodotoxin (a sodium channel blocker), nifedipine (a calcium channel blocker), and Ca²⁺-free Krebs-Henseleit solution with ethylene glycol tetraacetic acid (EGTA), followed by administration of cumulative dosages of SM extracts. SM extracts induced dose-related tonic contraction of the LES, which was unaffected by tetrodotoxin, atropine, or nifedipine. However, the SM extract-induced LES contraction was significantly inhibited by Ca²⁺-free Krebs-Henseleit solution with EGTA. Next, SM extracts significantly induce extracellular Ca²⁺ entry into primary LES cells in addition to intracellular Ca²⁺ release and in a dose-response manner. Confocal fluorescence microscopy showed that the SM extracts consistently induced significant extracellular Ca²⁺ influx into primary LES cells in a time-dependent manner. In conclusion, SM extracts could induce tonic contraction of LES mainly through the extracellular Ca²⁺ influx pathway. Full article

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Open AccessArticle

Management of Hyperglycaemia by Ethyl Acetate Extract of Balanites aegyptiaca (Desert Date)

by Abdulrahman L. Al-Malki, Elie K. Barbour, Kalid O. Abulnaja and Said S. Moselhy

Molecules 2015, 20(8), 14425-14434; https://doi.org/10.3390/molecules200814425 - 7 Aug 2015

Cited by 22 | Viewed by 6004

Abstract

Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve [...] Read more.

Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 µg/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-α), interleukin (IL-1β) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of β-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications. Full article

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Open AccessArticle

Isolation, Characterization, Crystal Structure Elucidation of Two Flavanones and Simultaneous RP-HPLC Determination of Five Major Compounds from Syzygium campanulatum Korth

by Abdul Hakeem Memon, Zhari Ismail, Fouad Saleih Resq Al-Suede, Abdalrahim F. A. Aisha, Mohammad Shahrul Ridzuan Hamil, Mohammed Ali Ahmed Saeed, Madeeha Laghari and Amin Malik Shah Abdul Majid

Molecules 2015, 20(8), 14212-14233; https://doi.org/10.3390/molecules200814212 - 4 Aug 2015

Cited by 28 | Viewed by 8789

Abstract

Two flavanones named (2S)-7-Hydroxy-5-methoxy-6,8-dimethyl flavanone (1), (S)-5,7-dihydroxy-6,8-dimethyl-flavanone (2), along with known chalcone, namely, (E)-2ʹ,4ʹ- dihydroxy-6ʹ-methoxy-3ʹ,5ʹ-dimethylchalcone (3) and two triterpenoids, namely, betulinic and ursolic acids (4 and 5), were isolated from the leaves of Syzygium campanulatum Korth (Myrtaceae). The structures of compounds (1 and [...] Read more.

Two flavanones named (2S)-7-Hydroxy-5-methoxy-6,8-dimethyl flavanone (1), (S)-5,7-dihydroxy-6,8-dimethyl-flavanone (2), along with known chalcone, namely, (E)-2ʹ,4ʹ- dihydroxy-6ʹ-methoxy-3ʹ,5ʹ-dimethylchalcone (3) and two triterpenoids, namely, betulinic and ursolic acids (4 and 5), were isolated from the leaves of Syzygium campanulatum Korth (Myrtaceae). The structures of compounds (1 and 2) were determined on the basis of UV-visible, FTIR, NMR spectroscopies and LC-EIMS analytical techniques. Furthermore, new, simple, precise, selective, accurate, highly sensitive, efficient and reproducible RP-HPLC method was developed and validated for the quantitative analysis of the compounds (1–5) from S. campanulatum plants of five different age. RP-HPLC method was validated in terms of specificity, linearity (r2 ≤ 0.999), precision (2.0% RSD), and recoveries (94.4%–105%). The LOD and LOQ of these compounds ranged from 0.13–0.38 and 0.10–2.23 μg·mL−1, OPEN ACCESS respectively. Anti-proliferative activity of isolated flavanones (1 and 2) and standardized extract of S. campanulatum was evaluated on human colon cancer (HCT 116) cell line. Compounds (1 and 2) and extract revealed potent and dose-dependent activity with IC50 67.6, 132.9 and 93.4 μg·mL−1, respectively. To the best of our knowledge, this is the first study on isolation, characterization, X-ray crystallographic analysis of compounds (1 and 2) and simultaneous RP-HPLC determination of five major compounds (1–5) from different age of S. campanulatum plants. Full article

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Open AccessArticle

Cordyceps militaris (L.) Link Fruiting Body Reduces the Growth of a Non-Small Cell Lung Cancer Cell Line by Increasing Cellular Levels of p53 and p21

by Ana Bizarro, Isabel C. F. R. Ferreira, Marina Soković, Leo J. L. D. Van Griensven, Diana Sousa, M. Helena Vasconcelos and Raquel T. Lima

Molecules 2015, 20(8), 13927-13940; https://doi.org/10.3390/molecules200813927 - 31 Jul 2015

Cited by 25 | Viewed by 10647

Abstract

Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human [...] Read more.

Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies. Full article

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Open AccessArticle

Identification of Eupatilin from Artemisia argyi as a Selective PPARα Agonist Using Affinity Selection Ultrafiltration LC-MS

by Yongsoo Choi, Yujung Jung and Su-Nam Kim

Molecules 2015, 20(8), 13753-13763; https://doi.org/10.3390/molecules200813753 - 28 Jul 2015

Cited by 34 | Viewed by 7888

Abstract

Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) are key nuclear receptors and therapeutic targets for the treatment of metabolic diseases through the regulation of insulin resistance, diabetes, and dyslipidemia. Although a few drugs that target PPARs have been approved, more diverse and novel PPAR ligands are necessary to improve the safety and efficacy of available drugs. To expedite the search for new natural agonists of PPARs, we developed a screening assay based on ultrafiltration liquid chromatography-mass spectrometry (LC-MS) that is compatible with complex samples such as dietary foods or botanical extracts. The known PPARα and/or PPARγ ligands resveratrol and rosiglitazone were used as positive controls to validate the developed method. When applied to the screening of an Artemisia argyi extract, eupatilin was identified as a selective PPARα ligand. A PPAR competitive binding assay based on FRET detection also confirmed eupatilin as a selective PPARα agonist exhibiting a binding affinity of 1.18 μM (IC₅₀). Furthermore, eupatilin activation of the transcriptional activity of PPARα was confirmed using a cell-based transactivation assay. Thus, ultrafiltration LC-MS is a suitable assay for the identification of PPAR ligands in complex matrixes such as extracts of dietary foods and botanicals. Full article

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Isolation and Identification of Cytotoxic Compounds from Aeschynomene fascicularis, a Mayan Medicinal Plant

by Edgar E. Caamal-Fuentes, Sergio R. Peraza-Sánchez, Luis W. Torres-Tapia and Rosa E. Moo-Puc

Molecules 2015, 20(8), 13563-13574; https://doi.org/10.3390/molecules200813563 - 24 Jul 2015

Cited by 30 | Viewed by 6284

Abstract

The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to [...] Read more.

The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer. Full article

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A Fungal α-Galactosidase from Tricholoma matsutake with Broad Substrate Specificity and Good Hydrolytic Activity on Raffinose Family Oligosaccharides

by Xueran Geng, Guoting Tian, Yongchang Zhao, Liyan Zhao, Hexiang Wang and Tzi Bun Ng

Molecules 2015, 20(8), 13550-13562; https://doi.org/10.3390/molecules200813550 - 24 Jul 2015

Cited by 23 | Viewed by 7288

Abstract

An acidic α-galactosidase designated as TMG was purified from the fruiting bodies The purification protocol entailed ion exchange chromatography on Q-Sepharose and of Tricholoma matsutake with 136-fold purification and a specific activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on Superdex [...] Read more.

An acidic α-galactosidase designated as TMG was purified from the fruiting bodies The purification protocol entailed ion exchange chromatography on Q-Sepharose and of Tricholoma matsutake with 136-fold purification and a specific activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on Superdex 75. TMG is a monomeric protein exhibiting a molecular mass of 47 kDa in SDS-PAGE and gel filtration. The purified enzyme was identified by LC-MS/MS and three inner amino acid sequences were obtained. The optimum pH and temperature for TMG with pNPGal as substrate were pH 4.5 and 55 °C, respectively. The α-galactosidase activity was strongly inhibited by K⁺, Ca²⁺, Cd²⁺, Hg²⁺, Ag⁺ and Zn²⁺ ions. The enzyme activity was inhibited by the chemical modification agent N-bromosuccinimide (NBS), indicating the importance of tryptophan residue(s) at or near the active site. Besides hydrolyzing pNPGal, TMG also efficaciously catalyzed the degradation of natural substrates such as stachyose, raffinose, and melibiose. Thus TMG can be exploited commercially for improving the nutritional value of soy milk by degradation of indigestible oligosaccharides. Full article

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Structure Elucidation of Procyanidins Isolated from Rhododendron formosanum and Their Anti-Oxidative and Anti-Bacterial Activities

by Chao-Min Wang, Yuan-Man Hsu, Yun-Lian Jhan, Shang-Jie Tsai, Shi-Xun Lin, Chiu-Hsian Su and Chang-Hung Chou

Molecules 2015, 20(7), 12787-12803; https://doi.org/10.3390/molecules200712787 - 15 Jul 2015

Cited by 41 | Viewed by 6715

Abstract

Rhododendron formosanum is an endemic species distributed in the central mountains of Taiwan. In this study, the biological activities of major procyanidins isolated from the leaf extract of R. formosanum were investigated. Four compounds, including two procyanidin dimers, procyanidin A1 (1) [...] Read more.

Rhododendron formosanum is an endemic species distributed in the central mountains of Taiwan. In this study, the biological activities of major procyanidins isolated from the leaf extract of R. formosanum were investigated. Four compounds, including two procyanidin dimers, procyanidin A1 (1) and B3 (2), and two procyanidin trimmers, procyanidin C4 (4) and cinnamtannin D1 (5), were isolated and identified on the basis of spectroscopic data. The structure of a new procyanidin dimer, rhodonidin A (3), was elucidated by 2D-NMR, CD spectrum and MS. The procyanidin trimmers and rhodonidin A are reported for the first time in Ericaceae. The biological activities of these procyanidins were evaluated using anti-bacterial and anti-oxidative assays. Only the new compound 3 demonstrated strong anti-bacterial activity against Staphylococcus aureus at an MIC value of 4 μg/mL. All compounds showed pronounced antioxidant activities and the activities are enhanced as the amount of OH groups in procyanidins increased. In conclusion, the pleiotropic effects of procyanidins isolated from the leaves of R. formosanum can be a source of promising compounds for the development of future pharmacological applications. Full article

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Open AccessCommunication

Enzyme Inhibitory Radicinol Derivative from Endophytic fungus Bipolaris sorokiniana LK12, Associated with Rhazya stricta

by Abdul Latif Khan, Liaqat Ali, Javid Hussain, Tania Shamim Rizvi, Ahmed Al-Harrasi and In-Jung Lee

Molecules 2015, 20(7), 12198-12208; https://doi.org/10.3390/molecules200712198 - 3 Jul 2015

Cited by 21 | Viewed by 6537

Abstract

Endophytes, living inside plant tissues, play an essential role in plant growth and development, whilst producing unique bioactive secondary metabolites. In the current study, the endophytic fungus Bipolaris sorokiniana LK12 was isolated from the leaves of ethno-medicinal and alkaloidal rich Rhazya stricta. The [...] Read more.

Endophytes, living inside plant tissues, play an essential role in plant growth and development, whilst producing unique bioactive secondary metabolites. In the current study, the endophytic fungus Bipolaris sorokiniana LK12 was isolated from the leaves of ethno-medicinal and alkaloidal rich Rhazya stricta. The bulk amount of ethyl acetate extract of fungus was subjected to advance column chromatographic techniques, which resulted in the isolation of a new radicinol derivative, bipolarisenol (1). It was found to be a derivative of radicinol. The structure elucidation was carried out by the combined use of 1D and 2D nuclear magnetic resonance, infrared spectroscopy, mass, and UV spectrometric analyses. The bipolarisenol was assessed for its potential role in enzyme inhibition of urease and acetyl cholinesterase (AChE). Results showed that bipolarisenol significantly inhibited the AChE activity with low IC₅₀ (67.23 ± 5.12 µg·mL⁻¹). Bipolarisenol inhibited urease in a dose-dependent manner with high IC₅₀ (81.62 ± 4.61 µg·mL⁻¹). The new compound also showed a moderate anti-lipid peroxidation potential (IC₅₀ = 168.91 ± 4.23 µg·mL⁻¹). In conclusion, endophytes isolated from medicinal plants possess a unique potential to be considered for future drug discovery. Full article

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Open AccessArticle

Chemical Characterization of Different Sumac and Pomegranate Extracts Effective against Botrytis cinerea Rots

by Flora V. Romeo, Gabriele Ballistreri, Simona Fabroni, Sonia Pangallo, Maria Giulia Li Destri Nicosia, Leonardo Schena and Paolo Rapisarda

Molecules 2015, 20(7), 11941-11958; https://doi.org/10.3390/molecules200711941 - 30 Jun 2015

Cited by 70 | Viewed by 9265

Abstract

Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were [...] Read more.

Pomegranate (Punica granatum L.) peel and sumac (Rhus coriaria L.) fruit and leaf extracts were chemically characterized and their ability to inhibit table grape (cv. Italia) rots caused by Botrytis cinerea was evaluated on artificially inoculated berries. Different extraction methods were applied and extracts were characterized through Ultra Fast High Performance Liquid Chromatography coupled to Photodiode array detector and Electrospray ionization Mass spectrometer (UPLC-PDA-ESI/MSⁿ) for their phenol and anthocyanin contents. The concentrated pomegranate peel extract (PGE-C) was the richest in phenols (66.97 g gallic acid equivalents/kg) while the concentrated sumac extract from fruits (SUF-C) showed the highest anthocyanin amount (171.96 mg cyanidin 3-glucoside equivalents/kg). Both phenolic and anthocyanin profile of pomegranate and sumac extracts were quite different: pomegranate extract was rich in cyanidin 3-glucoside, pelargonidin 3-glucoside and ellagic acid derivatives, while sumac extract was characterized by 7-methyl-cyanidin 3-galactoside and gallic acid derivatives. The concentrated extracts from both pomegranate peel and sumac leaves significantly reduced the development of Botrytis rots. In particular, the extract from pomegranate peel completely inhibited the pathogen at different intervals of time (0, 12, and 24 h) between treatment and pathogen inoculation on fruits maintained at 22–24 °C and high relative humidity (RH). This extract may represent a valuable alternative to control postharvest fungal rots in view of its high efficacy because of the low cost of pomegranate peel, which is a waste product of processing factories. Full article

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Open AccessArticle

Analysis of Flavonoids in Lotus (Nelumbo nucifera) Leaves and Their Antioxidant Activity Using Macroporous Resin Chromatography Coupled with LC-MS/MS and Antioxidant Biochemical Assays

by Ming-Zhi Zhu, Wei Wu, Li-Li Jiao, Ping-Fang Yang and Ming-Quan Guo

Molecules 2015, 20(6), 10553-10565; https://doi.org/10.3390/molecules200610553 - 8 Jun 2015

Cited by 113 | Viewed by 13634

Abstract

Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted [...] Read more.

Lotus (Nelumbo nucifera) leaves, a traditional Chinese medicinal herb, are rich in flavonoids. In an effort to thoroughly analyze their flavonoid components, macroporous resin chromatography coupled with HPLC-MS/MS was employed to simultaneously enrich and identify flavonoids from lotus leaves. Flavonoids extracted from lotus leaves were selectively enriched in the macroporous resin column, eluted subsequently as fraction II, and successively subjected to analysis with the HPLC-MS/MS and bioactivity assays. Altogether, fourteen flavonoids were identified, four of which were identified from lotus leaves for the first time, including quercetin 3-O-rhamnopyranosyl-(1→2)-glucopyranoside, quercetin 3-O-arabinoside, diosmetin 7-O-hexose, and isorhamnetin 3-O-arabino- pyranosyl-(1→2)-glucopyranoside. Further bioactivity assays revealed that these flavonoids from lotus leaves possess strong antioxidant activity, and demonstrate very good potential to be explored as food supplements or even pharmaceutical products to improve human health. Full article

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Open AccessArticle

γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells

by Khairunnisa' Md Yusof, Suzana Makpol, Rahman Jamal, Roslan Harun, Norfilza Mokhtar and Wan Zurinah Wan Ngah

Molecules 2015, 20(6), 10280-10297; https://doi.org/10.3390/molecules200610280 - 3 Jun 2015

Cited by 27 | Viewed by 10040

Abstract

Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect [...] Read more.

Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0–150 µg/mL) and 6G (0–300 µg/mL) on the cells. The half maximal inhibitory concentration (IC₅₀) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells. Full article

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Open AccessArticle

Isolation of an Angiotensin I-Converting Enzyme Inhibitory Protein with Antihypertensive Effect in Spontaneously Hypertensive Rats from the Edible Wild Mushroom Leucopaxillus tricolor

by Xueran Geng, Guoting Tian, Weiwei Zhang, Yongchang Zhao, Liyan Zhao, Mansok Ryu, Hexiang Wang and Tzi Bun Ng

Molecules 2015, 20(6), 10141-10153; https://doi.org/10.3390/molecules200610141 - 1 Jun 2015

Cited by 19 | Viewed by 7549

Abstract

An 86-kDa homodimeric angiotensin I-converting enzyme (ACE) inhibitory protein designated as LTP was isolated from fruit bodies of the mushroom Leucopaxillus tricolor. The isolation procedure involved ultrafiltration through a membrane with a molecular weight cutoff of 10-kDa, ion exchange chromatography on Q-Sepharose, [...] Read more.

An 86-kDa homodimeric angiotensin I-converting enzyme (ACE) inhibitory protein designated as LTP was isolated from fruit bodies of the mushroom Leucopaxillus tricolor. The isolation procedure involved ultrafiltration through a membrane with a molecular weight cutoff of 10-kDa, ion exchange chromatography on Q-Sepharose, and finally fast protein liquid chromatography-gel filtration on Superdex 75. LTP exhibited an IC₅₀ value of 1.64 mg∙mL⁻¹ for its ACE inhibitory activity. The unique N-terminal amino acid sequence of LTP was disclosed by Edman degradation to be DGPTMHRQAVADFKQ. In addition, seven internal sequences of LTP were elucidated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results of the Lineweaver-Burk plot suggested that LTP competitively inhibited ACE. Both LTP and the water extract of L. tricolor exhibited a clear antihypertensive effect on spontaneously hypertensive rats. Full article

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Open AccessCommunication

Inhibitory Effects of Verrucarin A on Tunicamycin-Induced ER Stress in FaO Rat Liver Cells

by Eun Young Bae, Seung Woong Lee, Sin Seong, Wonjun Cho, Jong Seog Ahn and Hyun-Sug Cho

Molecules 2015, 20(5), 8988-8996; https://doi.org/10.3390/molecules20058988 - 19 May 2015

Cited by 5 | Viewed by 7336

Abstract

Endoplasmic reticulum (ER) stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat [...] Read more.

Endoplasmic reticulum (ER) stress is linked with development and maintenance of cancer, and serves as a therapeutic target for treatment of cancer. Verrucarin A, isolated from the broth of Fusarium sp. F060190, showed potential inhibitory activity on tunicamycin-induced ER stress in FaO rat liver cells. In addition, the compound decreased tunicamycin-induced GRP78 promoter activity in a dose dependent manner without inducing significant inhibition of luciferase activity and cell growth for 6 and 12 h. Moreover, the compound decreased the expression of GRP78, CHOP, XBP-1, and suppressed XBP-1, and reduced phosphorylation of IRE1α in FaO rat liver cells. This evidence suggests for the first time that verrucarin A inhibited tunicamycin-induced ER stress in FaO rat liver cells. Full article

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Open AccessArticle

Effect of Extrusion Cooking on Bioactive Compounds in Encapsulated Red Cactus Pear Powder

by Martha G. Ruiz-Gutiérrez, Carlos A. Amaya-Guerra, Armando Quintero-Ramos, Esther Pérez-Carrillo, Teresita De J. Ruiz-Anchondo, Juan G. Báez-González and Carmen O. Meléndez-Pizarro

Molecules 2015, 20(5), 8875-8892; https://doi.org/10.3390/molecules20058875 - 18 May 2015

Cited by 32 | Viewed by 7706

Abstract

Red cactus pear has significant antioxidant activity and potential as a colorant in food, due to the presence of betalains. However, the betalains are highly thermolabile, and their application in thermal process, as extrusion cooking, should be evaluated. The aim of this study [...] Read more.

Red cactus pear has significant antioxidant activity and potential as a colorant in food, due to the presence of betalains. However, the betalains are highly thermolabile, and their application in thermal process, as extrusion cooking, should be evaluated. The aim of this study was to evaluate the effect of extrusion conditions on the chemical components of red cactus pear encapsulated powder. Cornstarch and encapsulated powder (2.5% w/w) were mixed and processed by extrusion at different barrel temperatures (80, 100, 120, 140 °C) and screw speeds (225, 275, 325 rpm) using a twin-screw extruder. Mean residence time (tr_m), color (L*, a*, b*), antioxidant activity, total polyphenol, betacyanin, and betaxanthin contents were determined on extrudates, and pigment degradation reaction rate constants (k) and activation energies (E_a) were calculated. Increases in barrel temperature and screw speed decreased the tr_m, and this was associated with better retentions of antioxidant activity, total polyphenol, betalain contents. The betacyanins k values ranged the −0.0188 to −0.0206/s and for betaxanthins ranged of −0.0122 to −0.0167/s, while E_a values were 1.5888 to 6.1815 kJ/mol, respectively. The bioactive compounds retention suggests that encapsulated powder can be used as pigments and to provide antioxidant properties to extruded products. Full article

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Open AccessArticle

Variety and Harvesting Season Effects on Antioxidant Activity and Vitamins Content of Citrus sinensis Macfad.

by Vanessa Cardeñosa, João C. M. Barreira, Lillian Barros, Francisco J. Arenas-Arenas, José M. Moreno-Rojas and Isabel C. F. R. Ferreira

Molecules 2015, 20(5), 8287-8302; https://doi.org/10.3390/molecules20058287 - 7 May 2015

Cited by 19 | Viewed by 6295

Abstract

Five sweet orange (Citrus sinensis Osbeck) varieties cultivated in Huelva (Spain) and picked at two seasons during two consecutive years, were characterized for their antioxidant activity (free radicals scavenging activity, reducing power and lipid peroxidation inhibition) and vitamin content (vitamin E and [...] Read more.

Five sweet orange (Citrus sinensis Osbeck) varieties cultivated in Huelva (Spain) and picked at two seasons during two consecutive years, were characterized for their antioxidant activity (free radicals scavenging activity, reducing power and lipid peroxidation inhibition) and vitamin content (vitamin E and vitamin C). The effects induced by sweet orange variety and stage of maturity were comprehensively compared by applying 2-way ANOVA and linear discriminant analysis. The results indicated higher differences in antioxidant activity and vitamin contents in response to the effect of the harvesting season, when compared to the effect of sweet orange variety. Nevertheless, the results observed in 2012 showed less marked differences among the assayed sweet orange varieties. Either way, it might be concluded that oranges sampled in January show the highest antioxidant activity and vitamin contents. Furthermore, concerning the properties evaluated in this work, all sweet orange varieties represent good alternatives, except for Rhode Summer, which would not be the preferable choice as a target to enhance sweet orange overall characteristics. Full article

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Open AccessArticle

Composition of the Essential Oil of Salvia ballotiflora (Lamiaceae) and Its Insecticidal Activity

by Norma Cecilia Cárdenas-Ortega, Marco Martín González-Chávez, Rodolfo Figueroa-Brito, Antonio Flores-Macías, Diana Romo-Asunción, Diana Elizabeth Martínez-González, Víctor Pérez-Moreno and Miguel Angel Ramos-López

Molecules 2015, 20(5), 8048-8059; https://doi.org/10.3390/molecules20058048 - 5 May 2015

Cited by 42 | Viewed by 7519

Abstract

Essential oils can be used as an alternative to using synthetic insecticides for pest management. Therefore, the insectistatic and insecticidal activities of the essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The [...] Read more.

Essential oils can be used as an alternative to using synthetic insecticides for pest management. Therefore, the insectistatic and insecticidal activities of the essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The results demonstrated insecticidal and insectistatical activities against this insect pest with concentrations at 80 µg·mL⁻¹ resulting in 20% larval viability and 10% pupal viability. The larval viability fifty (LV₅₀) corresponded to a concentration of 128.8 µg·mL⁻¹. This oil also increased the duration of the larval phase by 5.5 days and reduced the pupal weight by 29.2% withrespect to the control. The GC-MS analysis of the essential oil of S. ballotiflora showed its main components to be caryophyllene oxide (15.97%), and β-caryophyllene (12.74%), which showed insecticidal and insectistatical activities against S. frugiperda. The insecticidal activity of β-caryophyllene began at 80 µg·mL⁻¹, giving a larval viability of 25% and viability pupal of 20%. The insectistatic activity also started at 80 µg·mL⁻¹ reducing the pupal weight by 22.1% with respect to control. Caryophyllene oxide showed insecticidal activity at 80 µg·mL⁻¹ giving a larval viability of 35% and viability pupal of 20%.The insectistatic activity started at 400 µg·mL⁻¹ and increased the larval phase by 8.8% days with respect to control. The LV₅₀ values for these compounds were 153.1 and 146.5 µg·mL⁻¹, respectively. Full article

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Open AccessArticle

Antinociceptive Activity and Toxicity Evaluation of the Fatty Oil from Plukenetia polyadenia Mull. Arg. (Euphorbiaceae)

by Amanda S. Mota, Anderson B. De Lima, Thayana Lucy F. Albuquerque, Tiago S. Silveira, José Luiz M. do Nascimento, Joyce Kelly R. da Silva, Alcy F. Ribeiro, José Guilherme S. Maia and Gilmara N. T. Bastos

Molecules 2015, 20(5), 7925-7939; https://doi.org/10.3390/molecules20057925 - 30 Apr 2015

Cited by 12 | Viewed by 6278

Abstract

Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried seeds at room temperature to [...] Read more.

Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried seeds at room temperature to give a 47.0% yield of oil. It was then subjected to fatty acid composition analysis. The principal fatty acids were linoleic acid (46.5%), α-linolenic acid (34.4%) and oleic acid (13.9%). Then, it was evaluated for its antinociceptive activity in mice, using the acetic acid-induced abdominal writhing, hot plate and formalin test models. Additionally, its toxicity was determined. The Pp-oil proved to have no toxicological effects, showing dose-dependent antinociceptive effect under chemical stimulation. At oral doses of 25–100 mg/kg, Pp-oil significantly reduced the abdominal writhes in the writhing test. A higher oral dose of 200 mg/kg did not induce alterations in the latency time of the hot plate test when compared to the control, suggesting an analgesic activity of peripheral origin. At oral doses of 50 and 100 mg/kg, the Pp-oil significantly reduced the second phase of the algic stimulus in the formalin test. In addition, the antinociception of Pp-oil was reversed by naloxone in the evaluation of its mechanism of action. Therefore, the Pp-oil proved to be safe at very high doses and to show significant analgesic properties. The role of Pp-oil is still being investigated with respect the mechanism of action, but the results suggest that opiod receptors could be involved in the antinociception action observed for the oil of P. polyadenia. Full article

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Open AccessArticle

Inhibition of Oxidative Stress and Skin Aging-Related Enzymes by Prenylated Chalcones and Other Flavonoids from Helichrysum teretifolium

by Olugbenga K. Popoola, Jeanine L. Marnewick, Fanie Rautenbach, Farouk Ameer, Emmanuel I. Iwuoha and Ahmed A. Hussein

Molecules 2015, 20(4), 7143-7155; https://doi.org/10.3390/molecules20047143 - 20 Apr 2015

Cited by 67 | Viewed by 12566

Abstract

Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone ( [...] Read more.

Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (10) were isolated from a H. teretifolium methanolic extract and identified. One of them (compound 1) is reported for the first time from a natural source, while compounds 6, 8–10 were isolated for the first time from the genus Helichrysum. The total extract of H. teretifolium showed potent antioxidant activity. When tested for total antioxidant capacity compound 3 possesses moderate biological activity compared to 2, which displayed some of the highest TEAC values (4529.01 ± 2.44; 4170.66 ± 6.72) µM TE/g, respectively. Compounds 7 and 8 demonstrated the highest inhibitory activities on Fe²⁺-induced lipid peroxidation (IC₅₀ = 2.931; 6.449 µg/mL); tyrosinase (8.092; 27.573) and elastase (43.342; 86.548). Additionally, the total antioxidant capacities measured as FRAP (4816.31 ± 7.42; 3584.17 ± 0.54) µM AAE/g, and ORAC for hydroxyl radical (7.265 ± 0.71; 6.779 ± 3.40) × 10⁶ and peroxyl radical (17.836 ± 2.90; 12.545 ± 5.07) × 10³ µM TE/g were also observed for compounds 7 and 8, respectively. In conclusion, H. teretifolium total extract represents a rich source of bioactive constituents with potent antioxidant and moderate anti-tyrosinase and anti-elastase activities that can help to avert accumulation of free radicals in the body, and could therefore be good candidates for the prevention and/or treatment of skin-related conditions, such as aging. This is the first scientific report on the chemical and biological profile of H. teretifolium. Full article

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Open AccessArticle

Alkylamides of Acmella oleracea

by Yuan-Bin Cheng, Rosa Huang Liu, Meng-Chi Ho, Tung-Ying Wu, Ching-Yeu Chen, I-Wen Lo, Ming-Feng Hou, Shyng-Shiou Yuan, Yang-Chang Wu and Fang-Rong Chang

Molecules 2015, 20(4), 6970-6977; https://doi.org/10.3390/molecules20046970 - 16 Apr 2015

Cited by 36 | Viewed by 8883

Abstract

Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were [...] Read more.

Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established. Full article

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Open AccessReview

Studies on the Alkaloids of the Calycanthaceae and Their Syntheses

by Jin-Biao Xu and Ke-Jun Cheng

Molecules 2015, 20(4), 6715-6738; https://doi.org/10.3390/molecules20046715 - 15 Apr 2015

Cited by 26 | Viewed by 9240

Abstract

Plants of the Calycanthaceae family, which possesses four genera and about 15 species, are mainly distributed in China, North America and Australia. Chemical studies on the Calycanthaceae have led to the discovery of about 14 alkaloids of different skeletons, including dimeric piperidinoquinoline, dimeric [...] Read more.

Plants of the Calycanthaceae family, which possesses four genera and about 15 species, are mainly distributed in China, North America and Australia. Chemical studies on the Calycanthaceae have led to the discovery of about 14 alkaloids of different skeletons, including dimeric piperidinoquinoline, dimeric pyrrolidinoindoline and/or trimeric pyrrolidinoindolines, which exhibit significant anti-convulsant, anti-fungal, anti-viral analgesic, anti-tumor, and anti-melanogenesis activities. As some of complex tryptamine-derived alkaloids exhibit promising biological activities, the syntheses of these alkaloids have also been a topic of interest in synthetic chemistry during the last decades. This review will focus on the structures and total syntheses of these alkaloids. Full article

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Open AccessArticle

Simultaneous Determination of Five Components in Rat Plasma by UPLC–MS/MS and Its Application to a Comparative Pharmacokinetic Study in Baihe Zhimu Tang and Zhimu Extract

by Guolong Li, Zhishu Tang, Jie Yang, Jinao Duan, Dawei Qian, Jianming Guo, Zhenhua Zhu and Hongbo Liu

Molecules 2015, 20(4), 6700-6714; https://doi.org/10.3390/molecules20046700 - 15 Apr 2015

Cited by 23 | Viewed by 7068

Abstract

Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components [...] Read more.

Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components in Zhimu are flavonoids such as neomangiferin, mangiferin, and steroid saponins (e.g., timosaponin BII, anemarsaponin BIII, timosaponin AIII). The aim of this study was to compare the pharmacokinetics of mangiferin, neomangiferin, timosaponin BII, anemarsaponin BIII and timosaponin AIII in rat plasma after oral administration of BZT and Zhimu extract (ZME). A sensitive, reliable and robust LC-MS/MS method to simultaneously determine steroid saponins and flavonoids in rat plasma was successfully validated. Significant differences (p < 0.05) were found in the pharmacokinetic parameters of timosaponin BII, anemarsaponin BIII and timosaponin AIII between BZT and ZME. It was surmised that formula compatibility could significantly influence the pharmacokinetics of BZT and our study is the first to study the administration of BZT based on pharmacokinetic studies. Full article

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Open AccessArticle

An Ultra-High Performance Liquid Chromatographic-Tandem Mass Spectrometric Method for the Determination of Sinomenine in Human Plasma after Transdermal Delivery of the Zhengqing Fengtongning Injection

by Tingbo Chen, Zheng Xiang, Gengting Dong, Pei Luo, Ping Qiu, Shenzhi Wang, Baoming Huang, Yingyi Wen, Feichi Wu, Liang Liu and Hua Zhou

Molecules 2015, 20(4), 6454-6465; https://doi.org/10.3390/molecules20046454 - 10 Apr 2015

Cited by 8 | Viewed by 6625

Abstract

A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to [...] Read more.

A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract sinomenine. Separation was carried out on a C₁₈ column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for sinomenine quantification. The working assay range for sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained sinomenine within the concentration range 0.4131–4.407 ng/mL. Full article

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Open AccessArticle

Isolation, Identification and Cytotoxicity of a New Noroleanane-Type Triterpene Saponin from Salicornia bigelovii Torr.

by Fuqin Guan, Qizhi Wang, Ming Wang, Yu Shan, Yu Chen, Min Yin, Youyi Zhao, Xu Feng, Fei Liu and Jianhua Zhang

Molecules 2015, 20(4), 6419-6431; https://doi.org/10.3390/molecules20046419 - 10 Apr 2015

Cited by 9 | Viewed by 6579

Abstract

Salicornia bigelovii Torr. has been consumed not only as a popular kind of vegetable, but also as a medicinal plant to treat hypertension, cephalalgia, scurvy and cancer. The present study was designed to investigate its chemical components and cytotoxic activity. A new noroleanane-type [...] Read more.

Salicornia bigelovii Torr. has been consumed not only as a popular kind of vegetable, but also as a medicinal plant to treat hypertension, cephalalgia, scurvy and cancer. The present study was designed to investigate its chemical components and cytotoxic activity. A new noroleanane-type triterpene saponin, bigelovii C (1), was separated and purified from Salicornia bigelovii Torr., along with four known triterpene saponins 2–5. The structure of bigelovii C was elucidated as 3-O-(6-O-butyl ester)-β-D-glucuropyranosyl-23-aldehyde-30-norolean-12, 20 (29)-dien-28-oic acid-28-O-β-D-glucopyranoside, according to various spectroscopic analysis and chemical characteristics. Besides Compounds 3 and 5, bigelovii C had potent cytotoxicity against three human cancer cell lines, MCF7 (breast cancer), Lovo (colon cancer) and LN229 (glioblastoma), especially MCF7. Bigelovii C inhibited the growth of MCF7 cells in dose- and time-dependent manners. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased upon bigelovii C treatment. Rh123 staining assay indicated that bigelovii C reduced the mitochondrial membrane potential. The mechanism of cell death by bigelovii C may be attributed to the downregulation of Bcl-2 and upregulation of Bax, cleaved caspase-9, caspase-7 and PARP. These results suggested that bigelovii C may impart health benefits when consumed and should be regarded as a potential chemopreventative agent for cancer. Full article

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Open AccessArticle

Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide

by Michael Plöger, Jandirk Sendker, Klaus Langer and Thomas J. Schmidt

Molecules 2015, 20(4), 6211-6223; https://doi.org/10.3390/molecules20046211 - 9 Apr 2015

Cited by 12 | Viewed by 7084

Abstract

The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine [...] Read more.

The reactivity of parthenolide (PRT), a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae), with human serum albumin (HSA) was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine residue, C34, of HSA (0.6 mM) reacted readily with PRT when incubated at approximately 13-fold excess of PRT (8 mM). Time-course studies with PRT and its 11β,13-dihydro derivative at equimolar ratios of the reactants revealed that PRT under the chosen conditions reacts preferably with C34 and does so exclusively via its α-methylene-γ-lactone moiety, while the epoxide structure is not involved in the reaction. Full article

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Open AccessArticle

Biological Activities and Cytotoxicity of Diterpenes from Copaifera spp. Oleoresins

by Fabiano De S. Vargas, Patrícia D. O. de Almeida, Elenn Suzany P. Aranha, Ana Paula De A. Boleti, Peter Newton, Marne C. De Vasconcellos, Valdir F. Veiga Junior and Emerson S. Lima

Molecules 2015, 20(4), 6194-6210; https://doi.org/10.3390/molecules20046194 - 9 Apr 2015

Cited by 56 | Viewed by 8425

Abstract

Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity [...] Read more.

Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic, kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they show significant changes in viability of tumoral line cells. The 3-hydroxy-copalic was able to inhibit the enzyme tyrosinase (64% ± 1.5%) at 250 µM. The kolavic-15-metyl ester at 200 µM showed high inhibitory effect on lipoxygenase (89.5% ± 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids showed significant hemolytic activities with 61.7% and 38.4% at 100 µM, respectively. In addition, it was observed that only the copalic acid (98.5% ± 1.3%) and hardwickiic acid (92.7% ± 4.9%) at 100 mM inhibited nitric oxide production in macrophages activated by lipopolysaccharide. In this assay, the diterpenes did not inhibit tumor necrosis factor-α production. The acids inhibited the production of IL-6, 3-acetoxy-copalic (23.8% ± 8.2%), kaurenoic (11.2% ± 5.7%), kolavic-15-methyl ester (17.3% ± 4.2%), and copalic (4.2% ± 1.8%), respectively, at 25 µM. The kaurenoic, 3-acetoxy-copalic and copalic acids increased IL-10 production. This study may provide a basis for future studies on the therapeutic role of diterpenic acids in treating acute injuries such as inflammation or skin disorders. Full article

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Open AccessArticle

Evaluation of the Hypoglycemic Effects of Flavonoids and Extracts from Jatropha gossypifolia L.

by Sergio Granados, Norman Balcázar, Alis Guillén and Fernando Echeverri

Molecules 2015, 20(4), 6181-6193; https://doi.org/10.3390/molecules20046181 - 9 Apr 2015

Cited by 24 | Viewed by 7840

Abstract

Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose [...] Read more.

Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose uptake in C2C12 myotubes up to 30%, thereby reducing insulin resistance induced by fatty acids compared to the basal control. A chromatographic fraction applied intraperitoneally (IP) in mice reduced glucose by 42% in a mouse model of T2DM, after administration of 10 doses during 20 days. A flavanone was purified from this active fraction and its structure was assigned by ¹H- and ¹³C-NMR (1D and 2D) and MS. This compound retains the previously reported activity, stimulating in vitro the glucose uptake in a concentration-dependent manner. This study indicates that Jatropha gossypifolia L. extracts enhance glucose uptake in cultured myotubes and adipocytes and also improving glucose tolerance in an in vivo model. Full article

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Open AccessArticle

Stevia Rebaudiana Bert. Leaf Extracts as a Multifunctional Source of Natural Antioxidants

by Katarzyna Gaweł-Bęben, Tomasz Bujak, Zofia Nizioł-Łukaszewska, Beata Antosiewicz, Anna Jakubczyk, Monika Karaś and Kamila Rybczyńska

Molecules 2015, 20(4), 5468-5486; https://doi.org/10.3390/molecules20045468 - 27 Mar 2015

Cited by 103 | Viewed by 12507

Abstract

The aim of the presented study was to characterize the content and biological activity of extracts prepared from dried Stevia rebaudiana leaves with potential application in the food or cosmetic industry. Aqueous (A), ethanolic (E) and glycol-aqueous (GA) extracts were analyzed for the [...] Read more.

The aim of the presented study was to characterize the content and biological activity of extracts prepared from dried Stevia rebaudiana leaves with potential application in the food or cosmetic industry. Aqueous (A), ethanolic (E) and glycol-aqueous (GA) extracts were analyzed for the content of polyphenols and proteins, showing that the highest amount of phenols (15.50 mg/g) and flavonoids (3.85 mg/g) contained GA. All extracts contained significant amount of protein (69.40–374.67 mg/g). Between analyzed stevia extracts (HPLC) GA contained the highest amount of polyphenols, especially ferulic (5.50 mg/g) and rozmaric (4.95 mg/g) acids derivates. The highest antiradical activity against DPPH^• and ABTS^•+ was noted for GA and E (IC₅₀ = 0.38 and 0.71 µg flavonoids/mL). The highest ability to chelate Fe²⁺ was observed for E (IC₅₀ = 2.08 µg flavonoids/mL). Stevia extracts were also analyzed for their cytotoxicity and fibroblast irritation potential in vitro. E and GA were the most cytotoxic and irritating, probably due to the high content of biologically active phytochemicals. On the other hand, a extract was the most tolerable by the cells. To summarize, the presented study evaluated the potential application of A, E and GA stevia extracts as natural source of antioxidants in the food and cosmetic industry. Full article

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Open AccessArticle

Economical Synthesis of ¹³C-Labeled Opiates, Cocaine Derivatives and Selected Urinary Metabolites by Derivatization of the Natural Products

by Morten Karlsen, Huiling Liu, Jon Eigill Johansen and Bård Helge Hoff

Molecules 2015, 20(4), 5329-5345; https://doi.org/10.3390/molecules20045329 - 25 Mar 2015

Cited by 7 | Viewed by 23597

Abstract

The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, [...] Read more.

The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, ¹³C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-¹³C₄]heroin, [acetyl-¹³C₄-methyl-¹³C]heroin, [acetyl-¹³C₂-methyl-¹³C]6-acetylmorphine, [N-methyl-¹³C-O-metyl-¹³C]codeine and phenyl-¹³C₆-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying ¹³C atom-efficient routes towards these derivatives. Therefore, the ¹³C-labeled opiates and cocaine derivatives were made from the corresponding natural products. Full article

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Open AccessArticle

Neferine Attenuates the Protein Level and Toxicity of Mutant Huntingtin in PC-12 Cells via Induction of Autophagy

by Vincent Kam Wai Wong, An Guo Wu, Jing Rong Wang, Liang Liu and Betty Yuen-Kwan Law

Molecules 2015, 20(3), 3496-3514; https://doi.org/10.3390/molecules20033496 - 18 Feb 2015

Cited by 68 | Viewed by 9760

Abstract

Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through [...] Read more.

Mutant huntingtin aggregation is highly associated with the pathogenesis of Huntington’s disease, an adult-onset autosomal dominant disorder, which leads to a loss of motor control and decline in cognitive function. Recent literature has revealed the protective role of autophagy in neurodegenerative diseases through degradation of mutant toxic proteins, including huntingtin or a-synuclein. Through the GFP-LC3 autophagy detection platform, we have identified neferine, isolated from the lotus seed embryo of Nelumbo nucifera, which is able to induce autophagy through an AMPK-mTOR-dependent pathway. Furthermore, by overexpressing huntingtin with 74 CAG repeats (EGFP-HTT 74) in PC-12 cells, neferine reduces both the protein level and toxicity of mutant huntingtin through an autophagy-related gene 7 (Atg7)-dependent mechanism. With the variety of novel active compounds present in medicinal herbs, our current study suggests the possible protective mechanism of an autophagy inducer isolated from Chinese herbal medicine, which is crucial for its further development into a potential therapeutic agent for neurodegenerative disorders in the future. Full article

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Open AccessArticle

Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice

by Fernando P. Conte, Fausto K. Ferraris, Thadeu E. M. M. Costa, Patricia Pacheco, Leonardo N. Seito, Waldiceu A. Verri, Jr., Fernando Q. Cunha, Carmen Penido and Maria G. Henriques

Molecules 2015, 20(2), 2636-2657; https://doi.org/10.3390/molecules20022636 - 3 Feb 2015

Cited by 21 | Viewed by 7637

Abstract

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; [...] Read more.

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB₄, PGE₂, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations. Full article

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Open AccessArticle

Antimicrobial and Seasonal Evaluation of the Carvacrol-Chemotype Oil from Lippia origanoides Kunth.

by Sandra Layse F. Sarrazin, Leomara Andrade Da Silva, Ana Paula F. De Assunção, Ricardo B. Oliveira, Victor Y. P. Calao, Rodrigo Da Silva, Elena E. Stashenko, José Guilherme S. Maia and Rosa Helena V. Mourão

Molecules 2015, 20(2), 1860-1871; https://doi.org/10.3390/molecules20021860 - 23 Jan 2015

Cited by 52 | Viewed by 8578

Abstract

This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the [...] Read more.

This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the rainy season and 1.6% ± 0.3% in the dry season. Some correlations with climatic parameters were observed. The major components were carvacrol (rainy, 43.5% ± 1.9%; dry, 41.4% ± 2.04%), thymol (rainy, 10.7% ± 1.1%; dry, 10.6% ± 0.9%), p-cymene (rainy, 9.8% ± 0.7%; dry, 10.0% ± 1.4%) and p-methoxythymol (rainy, 9.6% ± 0.8%; dry, 10.4% ± 1.4%). It was found that the antibacterial activity of L. origanoides against Staphylococcus aureus and Escherichia coli was little influenced by the changes in oil composition due to seasonal variation. Against S. aureus, the oil Minimum Inhibitory Concentration (MIC) value was 1.25 μL/mL over ten months. Against E. coli, the oil MIC values ranged from 0.15 μL/mL to 0.31 μL/mL in different months of the year. The Minimum Bactericidal Concentration (MBC) value was 2.5 μL/mL against S. aureus and 1.25 μL/mL against E. coli. The results suggest that the antimicrobial activity identified in the oil remain unchanged for the full year, allowing its medicinal use without any risk of loss or absence of the active principles of the plant. Full article

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Open AccessArticle

Cytotoxic Activity and Composition of Petroleum Ether Extract from Magydaris tomentosa (Desf.) W. D. J. Koch (Apiaceae)

by Giuseppina Autore, Stefania Marzocco, Carmen Formisano, Maurizio Bruno, Sergio Rosselli, Mariem Ben Jemia and Felice Senatore

Molecules 2015, 20(1), 1571-1578; https://doi.org/10.3390/molecules20011571 - 16 Jan 2015

Cited by 30 | Viewed by 9420

Abstract

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative [...] Read more.

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative activity of Magydaris tomentosa flower extract has been evaluated in vitro on murine monocye/macrophages (J774A.1), human melanoma (A375) and human breast cancer (MCF-7) tumor cell lines, showing a major activity against the latter. Full article

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Open AccessReview

Halofuginone — The Multifaceted Molecule

by Mark Pines and Itai Spector

Molecules 2015, 20(1), 573-594; https://doi.org/10.3390/molecules20010573 - 5 Jan 2015

Cited by 99 | Viewed by 13282

Abstract

Halofuginone is an analog of febrifugine—an alkaloid originally isolated from the plant Dichroa febrifuga. During recent years, halofuginone has attracted much attention because of its wide range of beneficial biological activities, which encompass malaria, cancer, and fibrosis-related and autoimmune diseases. At present [...] Read more.

Halofuginone is an analog of febrifugine—an alkaloid originally isolated from the plant Dichroa febrifuga. During recent years, halofuginone has attracted much attention because of its wide range of beneficial biological activities, which encompass malaria, cancer, and fibrosis-related and autoimmune diseases. At present two modes of halofuginone actions have been described: (1) Inhibition of Smad3 phosphorylation downstream of the TGFβ signaling pathway results in inhibition of fibroblasts-to-myofibroblasts transition and fibrosis. (2) Inhibition of prolyl-tRNA synthetase (ProRS) activity in the blood stage of malaria and inhibition of Th17 cell differentiation thereby inhibiting inflammation and the autoimmune reaction by activation of the amino acid starvation and integrated stress responses. This review deals with the history and origin of this natural product, its synthesis, its known modes of action, and it’s various biological activities in pre-clinical animal models and in humans. Full article

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Open AccessCommunication

Characterization of Ambrette Seed Oil and Its Mode of Action in Bacteria

by Selvaraj Arokiyaraj, Seong Ho Choi, Yoonseok Lee, Rajaraman Bharanidharan, Villianur Ibrahim Hairul-Islam, Badathala Vijayakumar, Young Kyoon Oh, Vannam Dinesh-Kumar, Savariar Vincent and Kyoung Hoon Kim

Molecules 2015, 20(1), 384-395; https://doi.org/10.3390/molecules20010384 - 29 Dec 2014

Cited by 19 | Viewed by 8565

Abstract

In the present study, chemical composition and the antibacterial mechanism of ambrette seed oil are investigated. Chemical composition of the oil was analysed by gas chromatography-mass spectrometry (GC-MS). Thirty-five compounds were identified and the major compounds were found to be farnesol acetate (51.45%) [...] Read more.

In the present study, chemical composition and the antibacterial mechanism of ambrette seed oil are investigated. Chemical composition of the oil was analysed by gas chromatography-mass spectrometry (GC-MS). Thirty-five compounds were identified and the major compounds were found to be farnesol acetate (51.45%) and ambrettolide (12.96%). The antibacterial activity was performed by well diffusion assay and the mechanisms were studied by measuring the alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and protein leakage assays. The antibacterial effect of the ambrette seed oil showed inhibitory effect against Bacillus subtilis, Staphylococcus aureus and Enterococcus faecalis. The LDH activity was high in all tested bacteria compared with control, whereas the ALP and protein concentrations were also increased in E. faecalis. Molecular docking revealed the ligands farnesol acetate and ambrettolide had satisfactory binding energy towards the beta lactamase TEM-72 and dihydrofolate reductase (DHFR) protein. Due to its better antibacterial properties, the ambrette seed oil could be used as a source of antibacterial agents. Full article

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Open AccessArticle

Asperaculanes A and B, Two Sesquiterpenoids from the Fungus Aspergillus aculeatus

by Yu-Qi Gao, Chun-Jun Guo, Qiang Zhang, Wen-Ming Zhou, Clay C. C. Wang and Jin-Ming Gao

Molecules 2015, 20(1), 325-334; https://doi.org/10.3390/molecules20010325 - 25 Dec 2014

Cited by 17 | Viewed by 7565

Abstract

Six sesquiterpenoids 1–6, including two new ones, an ent-daucane-type sesquiterpenoid, asperaculane A (1), and a nordaucane one, asperaculane B (2), and four known nordaucane derivatives, aculenes A–D 3–6, together with the known [...] Read more.

Six sesquiterpenoids 1–6, including two new ones, an ent-daucane-type sesquiterpenoid, asperaculane A (1), and a nordaucane one, asperaculane B (2), and four known nordaucane derivatives, aculenes A–D 3–6, together with the known secalonic acid D (7), were isolated from a fermentation culture of the fungus Aspergillus aculeatus. Their structures and absolute configurations were established by analyses of their spectroscopic data, including 1D and 2D-NMR spectra, HR-ESIMS, electronic circular dichroism (ECD) data, and quantum chemical calculations. These metabolites were evaluated for in vitro cytotoxic activity against two cell lines, human cancer cell lines (HeLa) and one normal hamster cell line (CHO). Full article

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Open AccessArticle

Anti-Depressant-Like Effect of Kaempferitrin Isolated from Justicia spicigera Schltdl (Acanthaceae) in Two Behavior Models in Mice: Evidence for the Involvement of the Serotonergic System

by Julia Cassani, Ana María Dorantes-Barrón, Lilian Mayagoitia Novales, Guadalupe Alva Real and Rosa Estrada-Reyes

Molecules 2014, 19(12), 21442-21461; https://doi.org/10.3390/molecules191221442 - 19 Dec 2014

Cited by 49 | Viewed by 8893

Abstract

We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as “la tristeza” (sadness or dysthymia) and “el humor” (mood changes). The actions of Km were evaluated [...] Read more.

We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as “la tristeza” (sadness or dysthymia) and “el humor” (mood changes). The actions of Km were evaluated in a forced swimming test (FST) and a suspension tail test (TST) in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA) in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT) was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg) produced a synergistic effect with imipramine (6.25 mg/kg) and fluoxetine (10 mg/kg) but not with desipramine (3.12 mg/kg). Pretreatment with p-chlorophenylalanine methyl ester (PCPA), a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl)-1-piperazinyl}-N-(2-pyridinyl)cyclohexecarboxamide (WAY-100635), a selective 5-HT_1A receptor antagonist, and 8OH-DPAT, a selective 5-HT_1A agonist, but not pindolol (10 mg/kg) blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT_1A. This effect was not related to changes in locomotor activity. Full article

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Open AccessArticle

Chemical Constituents from Licania cruegeriana and Their Cardiovascular and Antiplatelet Effects

by Omar Estrada, Whendy Contreras, Giovana Acha, Eva Lucena, Whitney Venturini, Alfonso Cardozo and Claudia Alvarado-Castillo

Molecules 2014, 19(12), 21215-21225; https://doi.org/10.3390/molecules191221215 - 17 Dec 2014

Cited by 13 | Viewed by 6609

Abstract

Three new lupane-type triterpenoids: 6β,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6β,30-dihydroxybetulinic acid (5) and 6β-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, [...] Read more.

Three new lupane-type triterpenoids: 6β,30-dihydroxybetulinic acid glucopyranosyl ester (4), 6β,30-dihydroxybetulinic acid (5) and 6β-hydroxybetulinic acid (6), were isolated from Licania cruegeriana Urb. along with six known compounds. Their structures were elucidated on the basis of spectroscopic methods, including IR, ESIMS, 1D- and 2D-NMR experiments, as well as by comparison of their spectral data with those of related compounds. All compounds were evaluated in vivo for their effects on the mean arterial blood pressure (MABP) and heart rate (HR) of spontaneously hypertensive rats (SHR) and also in vitro for their capacity to inhibit the human platelet aggregation. None of the isolated flavonoids 1–3 showed cardiovascular effects on SHR and among the isolated triterpenoids 4–9 only 5 and 6 produced a significant reduction in MABP (60.1% and 17.2%, respectively) and an elevation in HR (11.0% and 41.2%, respectively). Compounds 3, 4, 5 and 6 were able to inhibit human platelet aggregation induced by ADP, collagen and arachidonic acid with different selectivity profiles. Full article

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Open AccessArticle

Evaluation of the Efficiency of Different Disruption Methods on Yeast Cell Wall Preparation for β-Glucan Isolation

by Anna Bzducha-Wróbel, Stanisław Błażejak, Anna Kawarska, Lidia Stasiak-Różańska, Iwona Gientka and Ewa Majewska

Molecules 2014, 19(12), 20941-20961; https://doi.org/10.3390/molecules191220941 - 15 Dec 2014

Cited by 76 | Viewed by 14436

Abstract

Selected methods for yeast cell disruption were evaluated to establish their suitability for cell wall preparation in the process of β-glucan isolation. The effect of different disruption methods on contents of total saccharides, β-glucans and proteins in the produced cell walls preparations was [...] Read more.

Selected methods for yeast cell disruption were evaluated to establish their suitability for cell wall preparation in the process of β-glucan isolation. The effect of different disruption methods on contents of total saccharides, β-glucans and proteins in the produced cell walls preparations was analyzed. The degree of cell wall purification from intracellular components was established on the basis of the ratio of solubilised material. The investigated methods included: cell exposure to hot water (autoclaving), thermally-induced autolysis, homogenization in a bead mill, sonication and their combinations. Experimental systems were prepared in water (pH 5.0 and pH 7.0) and Tris-HCl buffer (pH 8.0). The Saccharomyces cerevisiae yeast cell wall preparations with the highest degree of cytosol component release and purification of β-glucans were produced by 30 min of cell homogenization with zirconium-glass beads (0.5 mm in diameter). This was confirmed by the highest ratio of solubilised material (approx. 64%–67%). The thus-produced preparations contained ca. 60% of total saccharides, 13%–14% of β(1,3)/(1,6)-glucans, and approx. 35% of crude proteins. Similar results were obtained after autolysis coupled with bead milling as well as with sonication, but the time required for these processes was more than 24 h. Homogenization in a bead mill could be valuable for general isolation procedures because allows one to eliminate the different autolytic activity of various yeast strains. Full article

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Open AccessArticle

The Biological Activities of Cinnamon, Geranium and Lavender Essential Oils

by Monika Sienkiewicz, Anna Głowacka, Edward Kowalczyk, Anna Wiktorowska-Owczarek, Marta Jóźwiak-Bębenista and Monika Łysakowska

Molecules 2014, 19(12), 20929-20940; https://doi.org/10.3390/molecules191220929 - 12 Dec 2014

Cited by 54 | Viewed by 14023

Abstract

Acinetobacter sp. represent an important cause of nosocomial infections. Their resistance to some antibiotics, their ability to survive on inanimate surfaces in the hospital environment and their ability to produce biofilms contributes to their virulence. The aim of the study was to determine [...] Read more.

Acinetobacter sp. represent an important cause of nosocomial infections. Their resistance to some antibiotics, their ability to survive on inanimate surfaces in the hospital environment and their ability to produce biofilms contributes to their virulence. The aim of the study was to determine the antibacterial properties of cinnamon, lavender and geranium essential oils against bacteria of the genus Acinetobacter isolated from several clinical materials and from the hospital environment. A comprehensive evaluation of the susceptibility of Acinetobacter sp. clinical strains to recommended antibiotics was performed. The constituents of cinnamon, lavender and geranium essential oils were identified by GC-FID-MS analysis, and their Minimal Inhibitory Concentrations (MICs) against tested clinical strains were determined by the micro-dilution broth method. In addition, the effects of essential oils on the viability of human microvascular endothelial cells (HMEC-1) and glioblastoma cell line (T98G) were evaluated. Cinnamon bark oil was the most active against clinical and environmental strains of Acinetobacter baumannii with MIC values ranging from 0.5 to 2.5 µL/mL. The MIC values for geranium oil were between 7.5 and 9.5 µL/mL, and between 10.5 and 13.0 µL/mL for lavender oil. These essential oils can be best employed in the fight against infections caused by bacteria from Acinetobacter genus as components of formulations for hygiene and disinfection of hospital environment. Full article

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Open AccessArticle

Expanding Current Knowledge on the Chemical Composition and Antioxidant Activity of the Genus Lactarius

by Vanessa Vieira, Lillian Barros, Anabela Martins and Isabel C. F. R. Ferreira

Molecules 2014, 19(12), 20650-20663; https://doi.org/10.3390/molecules191220650 - 10 Dec 2014

Cited by 11 | Viewed by 6694

Abstract

Despite the presence of toxic compounds in inedible mushrooms, the question whether the chemical nutrients and non-nutrients compositions in edible and inedible Lactarius species are similar remains unanswered. To answer this question, Lactarius citriolens Pouzar and Lactarius turpis (Weinm.) Fr., two inedible species, [...] Read more.

Despite the presence of toxic compounds in inedible mushrooms, the question whether the chemical nutrients and non-nutrients compositions in edible and inedible Lactarius species are similar remains unanswered. To answer this question, Lactarius citriolens Pouzar and Lactarius turpis (Weinm.) Fr., two inedible species, were studied in order to obtain information about their chemical composition and bioactivity. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques coupled to different detectors. L. citriolens and L. turpis methanolic extracts were tested regarding antioxidant potential (reducing power, radical scavenging activity and lipid peroxidation inhibition). The composition of macronutrients varied among the two species, but the profiles were similar between them and among other Lactarius species; L. citriolens gave the highest energy contribution, saturated fatty acids and organic acids, while the L. turpis sample was richer in free sugars, mono- and polyunsaturated fatty acids, tocopherols and phenolic compounds. L. turpis methanolic extract showed the highest antioxidant activity. The absence of hepatoxicity of the methanolic extracts was confirmed in porcine liver primary cells (in vitro conditions). The present study provided new information about wild L. citriolens and L. turpis, comparing their chemical composition and antioxidant properties with other Lactarius species, and expanding the knowledge about this genus. Full article

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Open AccessReview

Role of Protease-Inhibitors in Ocular Diseases

by Nicola Pescosolido, Andrea Barbato, Antonia Pascarella, Rossella Giannotti, Martina Genzano and Marcella Nebbioso

Molecules 2014, 19(12), 20557-20569; https://doi.org/10.3390/molecules191220557 - 8 Dec 2014

Cited by 32 | Viewed by 8289

Abstract

It has been demonstrated that the balance between proteases and protease-inhibitors system plays a key role in maintaining cellular and tissue homeostasis. Indeed, its alteration has been involved in many ocular and systemic diseases. In particular, research has focused on keratoconus, corneal wounds [...] Read more.

It has been demonstrated that the balance between proteases and protease-inhibitors system plays a key role in maintaining cellular and tissue homeostasis. Indeed, its alteration has been involved in many ocular and systemic diseases. In particular, research has focused on keratoconus, corneal wounds and ulcers, keratitis, endophthalmitis, age-related macular degeneration, Sorsby fundus dystrophy, loss of nerve cells and photoreceptors during optic neuritis both in vivo and in vitro models. Protease-inhibitors have been extensively studied, rather than proteases, because they may represent a therapeutic approach for some ocular diseases. The protease-inhibitors mainly involved in the onset of the above-mentioned ocular pathologies are: α2-macroglobulin, α1-proteinase inhibitor (α1-PI), metalloproteinase inhibitor (TIMP), maspin, SERPINA3K, SERPINB13, secretory leukocyte protease inhibitor (SLPI), and calpeptin. This review is focused on the several characteristics of dysregulation of this system and, particularly, on a possible role of proteases and protease-inhibitors in molecular remodeling that may lead to some ocular diseases. Recently, researchers have even hypothesized a possible therapeutic effect of the protease-inhibitors in the treatment of injured eye in animal models. Full article

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Open AccessArticle

Biflavans, Flavonoids, and a Dihydrochalcone from the Stem Wood of Muntingia calabura and Their Inhibitory Activities on Neutrophil Pro-Inflammatory Responses

by Wen-Lung Kuo, Hsiang-Ruei Liao and Jih-Jung Chen

Molecules 2014, 19(12), 20521-20535; https://doi.org/10.3390/molecules191220521 - 8 Dec 2014

Cited by 22 | Viewed by 7486

Abstract

Muntingia calabura (Tiliaceae) is commercially used in healthcare for the improvement of hypertension, myocardial infarction, spasm, and inflammatory conditions. Its fruits can be processed into jam and the leaves can be used for making tea. In the work reported herein a new biflavan, [...] Read more.

Muntingia calabura (Tiliaceae) is commercially used in healthcare for the improvement of hypertension, myocardial infarction, spasm, and inflammatory conditions. Its fruits can be processed into jam and the leaves can be used for making tea. In the work reported herein a new biflavan, (M),(2S),(2''S)-,(P),(2S),(2''S)-7,8,3',4',5',7'',8'',3''',4''',5'''-decamethoxy-5,5'' biflavan (1), a new flavone, 4'-hydroxy-7,8,3',5'-tetramethoxyflavone (2), and a new dihydrochalcone, (R)-2',β-dihydroxy-3',4'-dimethoxydihydrochalcone (3), have been isolated from the stem wood of M. calabura, together with 12 known compounds (4–15). The structures of these new compounds were elucidated by the interpretations of extensive spectroscopic data. Among the isolated compounds, 5-hydroxy-7-methoxyflavone (5), quercetin (6), and (2S)-7-hydroxyflavanone (10) exhibited potent inhibition of fMLP-induced superoxide anion generation by human neutrophils, with IC₅₀ values of 1.77 ± 0.70, 3.82 ± 0.46, and 4.92 ± 1.71 μM, respectively. Full article

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Open AccessCommunication

Saikosaponin D Isolated from Bupleurum falcatum Inhibits Selectin-Mediated Cell Adhesion

by Myoung-Jun Jang, Ye Sol Kim, Eun Young Bae, Tae-Seok Oh, Hwa-Jung Choi, Jung-Hee Lee, Hyun-Mee Oh and Seung Woong Lee

Molecules 2014, 19(12), 20340-20349; https://doi.org/10.3390/molecules191220340 - 4 Dec 2014

Cited by 11 | Viewed by 7374

Abstract

Three saikosaponins were isolated from the MeOH extract of the roots of Bupleurum falcatum L.: saikosaponins B3 (1); B4 (2); and D (3). Of the three, compound 3 inhibited the interaction of selectins (E, L, and P) [...] Read more.

Three saikosaponins were isolated from the MeOH extract of the roots of Bupleurum falcatum L.: saikosaponins B3 (1); B4 (2); and D (3). Of the three, compound 3 inhibited the interaction of selectins (E, L, and P) and THP-1 cells with IC₅₀ values of 1.8, 3.0 and 4.3 µM, respectively. Also, the aglycone structure 4 of compound 3 showed moderate inhibitory activity on L-selectin-mediated cell adhesion. From these results, we suspect that compound 3 isolated from Bupleurum falcatum roots would be a good candidate for therapeutic strategies to treat inflammation. Full article

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Open AccessArticle

Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

by Aldo F. Clemente-Soto, Isaías Balderas-Rentería, Gildardo Rivera, Aldo Segura-Cabrera, Elvira Garza-González and María Del Rayo Camacho-Corona

Molecules 2014, 19(12), 20170-20182; https://doi.org/10.3390/molecules191220170 - 2 Dec 2014

Cited by 21 | Viewed by 7865

Abstract

The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene [...] Read more.

The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents. Full article

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Open AccessArticle

Anti-Proliferative Effects of Siegesbeckia orientalis Ethanol Extract on Human Endometrial RL-95 Cancer Cells

by Chi-Chang Chang, Hsia-Fen Hsu, Kuo-Hung Huang, Jing-Mei Wu, Shyh-Ming Kuo, Xue-Hua Ling and Jer-Yiing Houng

Molecules 2014, 19(12), 19980-19994; https://doi.org/10.3390/molecules191219980 - 1 Dec 2014

Cited by 24 | Viewed by 8474

Abstract

Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and [...] Read more.

Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE) significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer), Hep G2 (hepatoma), FaDu (pharynx squamous cancer), MDA-MB-231 (breast cancer), and especially on LNCaP (prostate cancer) cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer. Full article

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Open AccessArticle

Antibacterial and EGFR-Tyrosine Kinase Inhibitory Activities of Polyhydroxylated Xanthones from Garcinia succifolia

by Susawat Duangsrisai, Kiattawee Choowongkomon, Lucinda J. Bessa, Paulo M. Costa, Nurmuhammat Amat and Anake Kijjoa

Molecules 2014, 19(12), 19923-19934; https://doi.org/10.3390/molecules191219923 - 28 Nov 2014

Cited by 19 | Viewed by 7558

Abstract

Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae) led to the isolation of 1,5-dihydroxyxanthone (1), 1,7-dihydroxyxanthone (2), 1,3,7-trihydroxyxanthone (3), 1,5,6-trihydroxyxanthone (4), 1,6,7-trihydroxyxanthone (5), and 1,3,6,7-tetrahydroxyxanthone (6 [...] Read more.

Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae) led to the isolation of 1,5-dihydroxyxanthone (1), 1,7-dihydroxyxanthone (2), 1,3,7-trihydroxyxanthone (3), 1,5,6-trihydroxyxanthone (4), 1,6,7-trihydroxyxanthone (5), and 1,3,6,7-tetrahydroxyxanthone (6). All of the isolated xanthones were evaluated for their antibacterial activity against bacterial reference strains, two Gram-positive (Staphylococcus aureus ATTC 25923, Bacillus subtillis ATCC 6633) and two Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853), and environmental drug-resistant isolates (S. aureus B1, Enteroccoccus faecalis W1, and E. coli G1), as well as for their epidermal growth factor receptor (EGFR) of tyrosine kinase inhibitory activity. Only 1,5,6-trihydroxy-(4), 1,6,7-trihydroxy-(5), and 1,3,6,7-tetrahydroxyxanthones (6) exhibited antibacterial activity against Gram-positive bacteria, however none was active against vancomycin-resistant E. faecalis. Additionally, 1,7-dihydroxyxanthone (2) showed synergism with oxacillin, but not with ampicillin. On the other hand, only 1,5-dihydroxyxanthone (1) and 1,7-dihydroxyxanthone (2) were found to exhibit the EGFR-tyrosine kinase inhibitory activity, with IC₅₀values of 90.34 and 223 nM, respectively. Full article

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Open AccessArticle

Mechanisms Underlying Vasorelaxation Induced in Rat Aorta by Galetin 3,6-Dimethyl Ether, a Flavonoid from Piptadenia stipulacea (Benth.) Ducke

by Cibério L. Macêdo, Luiz H. C. Vasconcelos, Ana C. De C. Correia, Italo R. R. Martins, Daysianne P. De Lira, Bárbara V. De O. Santos, Fabiana De A. Cavalcante and Bagnólia A. Da Silva

Molecules 2014, 19(12), 19678-19695; https://doi.org/10.3390/molecules191219678 - 27 Nov 2014

Cited by 12 | Viewed by 7521

Abstract

In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe)-induced contractions (pD₂ = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe [...] Read more.

In this study, we investigated the relaxant action of galetin 3,6-dimethyl ether (FGAL) on rat aorta. The flavonoid relaxed both PMA‑ and phenylephrine (Phe)-induced contractions (pD₂ = 5.36 ± 0.11 and 4.17 ± 0.10, respectively), suggesting the involvement of PKC and Phe pathways or α₁ adrenergic receptor blockade. FGAL inhibited and rightward shifted Phe-induced cumulative contraction‑response curves, indicating a noncompetitive antagonism of α₁ adrenergic receptors. The flavonoid was more potent in relaxing 30 mM KCl- than 80 mM KCl-induced contractions (pD₂ = 5.50 ± 0.22 and 4.37 ± 0.12). The vasorelaxant potency of FGAL on Phe-induced contraction was reduced in the presence of 10 mM TEA⁺. Furthermore, in the presence of apamin, glibenclamide, BaCl₂ or 4-AP, FGAL-induced relaxation was attenuated, indicating the participation of small conductance calcium-activated K⁺ channels (SK_Ca), ATP-sensitive K⁺ channels (K_ATP), inward rectifier K⁺ channels (K_ir) and voltage-dependent K⁺ channels (K_V), respectively. FGAL inhibited and rightward shifted CaCl₂-induced cumulative contraction-response curves in both depolarizing medium (high K⁺) and in the presence of verapamil and phenylephrine, suggesting inhibition of Ca²⁺ influx through voltage-gated calcium channels (Ca_V) and receptor operated channels (ROCs), respectively. Likewise, FGAL inhibited Phe-induced contractions in Ca²⁺-free medium, indicating inhibition of Ca²⁺ release from the sarcoplasmic reticulum (SR). FGAL potentiated the relaxant effect of aminophylline and sildenafil but not milrinone, suggesting the involvement of phosphodiesterase V (PDE V). Thus, the FGAL vasorelaxant mechanism involves noncompetitive antagonism of α₁ adrenergic receptors, the non-selective opening of K⁺ channels, inhibition of Ca²⁺ influx through Ca_V or ROCs and the inhibition of intracellular Ca²⁺ release. Additionally, there is the involvement of cyclic nucleotide pathway, particularly through PDE V inhibition. Full article

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Open AccessArticle

Synthesis, Anticancer and Antibacterial Activity of Salinomycin N-Benzyl Amides

by Michał Antoszczak, Ewa Maj, Agnieszka Napiórkowska, Joanna Stefańska, Ewa Augustynowicz-Kopeć, Joanna Wietrzyk, Jan Janczak, Bogumil Brzezinski and Adam Huczyński

Molecules 2014, 19(12), 19435-19459; https://doi.org/10.3390/molecules191219435 - 25 Nov 2014

Cited by 47 | Viewed by 9596

Abstract

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal [...] Read more.

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position. Full article

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Open AccessArticle

Anti-Cholinesterase Activity of Lycopodium Alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis

by Nguyen Ngoc Chuong, Nguyen Thi Thu Huong, Tran Manh Hung and Tran Cong Luan

Molecules 2014, 19(11), 19172-19179; https://doi.org/10.3390/molecules191119172 - 19 Nov 2014

Cited by 18 | Viewed by 8630

Abstract

A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. [...] Read more.

A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC₅₀ value of 54.3 μg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC₅₀ value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors. Full article

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Open AccessArticle

Essential Oil of Eucalyptus Gunnii Hook. As a Novel Source of Antioxidant, Antimutagenic and Antibacterial Agents

by Dušan Bugarin, Slavenko Grbović, Dejan Orčič, Dragana Mitić-Ćulafić, Jelena Knežević-Vukčević and Neda Mimica-Dukić

Molecules 2014, 19(11), 19007-19020; https://doi.org/10.3390/molecules191119007 - 18 Nov 2014

Cited by 19 | Viewed by 8015

Abstract

The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and [...] Read more.

The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and α-pinene (14.12%) were the major compounds comprising almost 82% of total EO. EO exhibited moderate DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, with IC₅₀ value of 7.19 µL/mL. The antimutagenic properties were assayed against the spontaneous and t-BOOH-induced mutagenesis in Escherichia coli IC202 oxyR mutant strain, deficient in removing radical oxygen species (ROS). Reduction of the spontaneous mutagenesis in the presence of E. gunnii EO was only slight, up to 12% at the highest concentration tested. However, when the oxidative mutagen was used, EO displayed more significant reduction of mutagenesis (maximum 23%) in a concentration dependent manner. Antibacterial activity was tested against the selected strains from ATTC and NCIB collections: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Micrococcus flavus, Klebsiella pneumoniae, and the two Escherichia coli strains from our laboratory collection (SY252 and IB112) using both the disk-diffusion and MIC assays. The greatest sensitivity was shown by M. flavus, K. pneumoniae and E. coli lpcA (MIC = 0.83 mg/mL), while the highest resistance was shown by E. coli (ATTC 25922) and S. epidermidis. This study represents the first report on chemical composition and biological activity of the Eucalyptus gunnii in the South Balkan region and beyond. Full article

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Open AccessArticle

The Antiosteoporotic Activity of Central-Icaritin (CIT) on Bone Metabolism of Ovariectomized Rats

by Jun Jiang, Jie Li and Xiaobin Jia

Molecules 2014, 19(11), 18690-18704; https://doi.org/10.3390/molecules191118690 - 14 Nov 2014

Cited by 19 | Viewed by 7002

Abstract

Central-icaritin (CIT) is a flavonoid aglycone first discovered in our laboratory, which is an isomeric aglycone of icaritin (IT). We wanted to know whether CIT also had anti-osteoporosis activity. In this study, CIT was investigated in an ovariectomized rat (OVX) model. Fifty-six 6-month [...] Read more.

Central-icaritin (CIT) is a flavonoid aglycone first discovered in our laboratory, which is an isomeric aglycone of icaritin (IT). We wanted to know whether CIT also had anti-osteoporosis activity. In this study, CIT was investigated in an ovariectomized rat (OVX) model. Fifty-six 6-month old female Sprague-Dawley rats were randomly assigned to sham operated group (Sham) and six OVX subgroups (n = 8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), icaritin (IT, 40 mg/kg body weight/day), estradiol valerate (EV, 100 μg/kg body weight/day) or CIT (10, 20, and 40 mg/kg body weight/day) for 12 weeks, respectively. Then, the serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone immunohistochemistry and related protein and gene expressions were evaluated. In OVX rats, the increases of body weight, HOP, AKP, and TRACP5b levels, and the decreases of uterus wet weight, femurs weight, BMD, serum OPG/RANKL and OCN were significantly inhibited by CIT treatment. Micro-CT analysis results showed that CIT apparently enhanced trabecular bone compared with the OVX group (p < 0.05). Total femur BMD and biomechanical strength of tibia were significantly improved (p < 0.05) after 12 weeks of CIT administration. In addition, the CIT administration also significantly enhanced the OPG expression, whereas reduced the RANKL expression in femurs according to RT-PCR, western blot assays and immunohistochemical evaluation. CIT had the antiosteoporotic activity, and its antiosteoporotic effects in OVX rats may be stronger than that of IT. Full article

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Open AccessArticle

In Vitro Proliferation and Production of Cytokine and IgG by Human PBMCs Stimulated with Polysaccharide Extract from Plants Endemic to Gabon

by Line Edwige Mengome, Aline Voxeur, Jean Paul Akue and Patrice Lerouge

Molecules 2014, 19(11), 18543-18557; https://doi.org/10.3390/molecules191118543 - 13 Nov 2014

Cited by 6 | Viewed by 8576

Abstract

Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5 × 10⁵ cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared [...] Read more.

Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5 × 10⁵ cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared with lipopolysaccharides (LPS) and concanavalin A (ConA) from healthy volunteers. The culture supernatants were used for cytokine and IgG detection by enzyme-linked immunosorbent assay (ELISA). The results show that pectin and hemicellulose extracts from Uvaria klainei, Petersianthus macrocarpus, Trichoscypha addonii, Aphanocalyx microphyllus, Librevillea klaineana, Neochevalierodendron stephanii and Scorodophloeus zenkeri induced production levels that were variable from one individual to another for IL-12 (3–40 pg/mL), IL-10 (6–443 pg/mL), IL-6 (7–370 pg/mL), GM-CSF (3–170 pg/mL) and IFN-γ (5–80 pg/mL). Only hemicelluloses from Aphanocalyx microphyllus produce a small amount of IgG (OD = 0.034), while the proliferation of cells stimulated with these polysaccharides increased up to 318% above the proliferation of unstimulated cells. However, this proliferation of PBMCs was abolished when the pectin of some of these plants was treated with endopolygalacturonase (p < 0.05), but the trend of cytokine synthesis remained the same, both before and after enzymatic treatment or saponification. This study suggests that these polysaccharides stimulate cells in a structure-dependent manner. The rhamnogalacturonan-I (RGI) fragment alone was not able to induce the proliferation of PBMC. Full article

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Open AccessArticle

External Application of the Volatile Oil from Blumea balsamifera May Be Safe for Liver — A Study on Its Chemical Composition and Hepatotoxicity

by Yu-Xin Pang, Zuo-Wang Fan, Dan Wang, Quan Yang, Kai Wang, Xiao-Lu Chen, Xuan Hu, Fu-Lai Yu and Zhen-Xia Chen

Molecules 2014, 19(11), 18479-18492; https://doi.org/10.3390/molecules191118479 - 13 Nov 2014

Cited by 14 | Viewed by 9301

Abstract

Ainaxiang (Blumea balsamifera), also known as Sambong, is an important ancient medicinal herb in Southeast Asia. It is rich in volatile oil, and still widely used nowadays for skin wound healing and treatment of sore throats. We analyzed the volatile oil [...] Read more.

Ainaxiang (Blumea balsamifera), also known as Sambong, is an important ancient medicinal herb in Southeast Asia. It is rich in volatile oil, and still widely used nowadays for skin wound healing and treatment of sore throats. We analyzed the volatile oil from Blumea balsamifera (BB oil) by gas chromatography-mass spectrometry (GC-MS). Forty one components, including l-borneol, were identified. Next, the damaging effects of BB oil diluted with olive oil on liver at different concentrations (100%, 50%, 20%), were evaluated, using both normal and wounded skin. Plasma ALT, AST, ALP and TBili were assessed, along with liver histopathology. The results showed that serum levels of liver toxicity markers in the high concentration groups (100% w/v) increased compared with control groups, whereas no significant changes was observed in histopathology of liver samples. In the wound groups, treatment with BB oil resulted in a decrease in serum toxicity index, compared with normal animal groups. This study confirms the safety of short term BB oil consumption, though high BB oil doses may lead to mild liver injury and this response might be weakened in the case of cutaneous wounds. These results are expected to be helpful for guiding appropriate therapeutic use of BB oil. Full article

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Open AccessArticle

In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao

by Zainal Baharum, Abdah Md Akim, Yun Hin Taufiq-Yap, Roslida Abdul Hamid and Rosmin Kasran

Molecules 2014, 19(11), 18317-18331; https://doi.org/10.3390/molecules191118317 - 10 Nov 2014

Cited by 72 | Viewed by 12645

Abstract

The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances [...] Read more.

The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC₅₀) was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC₅₀) = 41.4 ± 3.3 µg/mL]. Given the overall high IC₅₀ for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts. Full article

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Open AccessArticle

Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995): Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

by Dong-Cheol Kim, Hee-Suk Lee, Wonmin Ko, Dong-Sung Lee, Jae Hak Sohn, Joung Han Yim, Youn-Chul Kim and Hyuncheol Oh

Molecules 2014, 19(11), 18073-18089; https://doi.org/10.3390/molecules191118073 - 5 Nov 2014

Cited by 37 | Viewed by 9275

Abstract

In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) [...] Read more.

In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E₂ (PGE₂) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 μM to 80 μM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases. Full article

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Open AccessArticle

Dysidinoid A, an Unusual Meroterpenoid with Anti-MRSA Activity from the South China Sea Sponge Dysidea sp.

by Wei-Hua Jiao, Jing Li, Qian Liu, Ting-Ting Xu, Guo-Hua Shi, Hao-Bing Yu, Fan Yang, Bing-Nan Han, Min Li and Hou-Wen Lin

Molecules 2014, 19(11), 18025-18032; https://doi.org/10.3390/molecules191118025 - 5 Nov 2014

Cited by 16 | Viewed by 7138

Abstract

An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid [...] Read more.

An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5-dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA) with MIC₉₀ values of 8.0 μg/mL against both. Full article

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Open AccessArticle

Flavonoids from Gynostemma pentaphyllum Exhibit Differential Induction of Cell Cycle Arrest in H460 and A549 Cancer Cells

by Ko-Chung Tsui, Tzu-Hsuan Chiang, Jinn-Shyan Wang, Li-Ju Lin, Wei-Chih Chao, Bing-Huei Chen and Jyh-Feng Lu

Molecules 2014, 19(11), 17663-17681; https://doi.org/10.3390/molecules191117663 - 31 Oct 2014

Cited by 35 | Viewed by 16101

Abstract

Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to [...] Read more.

Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to exhibit antiproliferation effects against H460 cells (IC₅₀ = 50.2 μg/mL), although the IC₅₀ of H460 is 2.5-fold that of A549 cells (IC₅₀ = 19.8 μg/mL). Further investigation revealed that H460 cells are more susceptible to kaempferol than A549, whereas A549 cell growth is better inhibited by kaempferol rhamnohexoside derivatives as compared with H460. In addition, flavonoids from G. pentaphyllum induced cell cycle arrest at both S and G2/M phases with concurrent modulated expression of the cellular proteins cyclin A, B, p53 and p21 in A549 cells, but not H460. On the contrary, apoptosis and concomitant alteration in balance of BCL-2 and BAX expression as well as activation of caspase-3 were equally affected between both cells by flavonoid treatment. These observations strongly suggest the growth inhibition discrepancy between H460 and A549 following flavonoid treatment can be attributed to the lack of cell cycle arrest in H460 cells and the differences between H460 and A549 cells may serve as contrasting models for further mechanistic investigations. Full article

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Open AccessArticle

Changes in Phytochemical Synthesis, Chalcone Synthase Activity and Pharmaceutical Qualities of Sabah Snake Grass (Clinacanthus nutans L.) in Relation to Plant Age

by Ali Ghasemzadeh, Alireza Nasiri, Hawa Z. E. Jaafar, Ali Baghdadi and Izham Ahmad

Molecules 2014, 19(11), 17632-17648; https://doi.org/10.3390/molecules191117632 - 30 Oct 2014

Cited by 76 | Viewed by 11910

Abstract

In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS, [...] Read more.

In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS, EC 2.3.1.74) was measured, as it is a key enzyme for flavonoid production. Significant differences in total flavonoid (TF) production were observed between the three plant growth periods and the different plant parts. The highest contents of TF (6.32 mg/g dry weight [DW]) and total phenolic (TP) (18.21 mg/g DW) were recorded in 6-month-old buds. Among the flavonoids isolated in this study the most important ones based on concentration were from high to low as follows: catechin > quercetin > kaempferol > luteolin. Production of phenolic acids increased from 1 to 6 months, but after 6 months up to 1 year of age, they decreased significantly. The highest contents of caffeic acid (0.307 mg/g DW) and gallic acid (5.96 mg/g DW) were recorded in 1-year and 6-month-old buds, respectively. The lowest and highest activity of CHS was recorded in 1-month and 6-month-old buds with values of 3.6 and 9.5 nkat/mg protein, respectively. These results indicate that the increment in flavonoids and phenolic acids in 6-month-old buds can be attributed to an increase in CHS activity. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity was observed in the extract of 1-year-old buds followed by 6-month-old buds, with 50% of free radical scavenging (IC₅₀) values of 64.6 and 73.5 µg/mL, respectively. Interestingly, a ferric reducing antioxidant power (FRAP) assay showed a higher activity in 6-month-old buds (488 μM of Fe(II)/g) than in 1-year-old buds (453 μM of Fe(II)/g), in contrast to the DPPH result. Significant correlations (p < 0.05) were observed between CHS enzyme activity and FRAP activity, TF, catechin, and kaempferol content. Extracts of 6-month-old bud exhibited a significant in vitro anticancer activity against HeLa cancer cells with IC₅₀ value of 56.8 µg/mL. These results indicate that early harvesting of snake grass (6-month-old) may yield increased concentrations of secondary metabolites, which are potent antioxidant compounds. Full article

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Open AccessArticle

Carapanolides J–L from the Seeds of Carapa guianensis (Andiroba) and Their Effects on LPS-Activated NO Production

by Yuuki Matsui, Takashi Kikuchi, Takanobu Inoue, Osamu Muraoka, Takeshi Yamada and Reiko Tanaka

Molecules 2014, 19(11), 17130-17140; https://doi.org/10.3390/molecules191117130 - 24 Oct 2014

Cited by 26 | Viewed by 6940

Abstract

A novel gedunin and two novel phragmalin-type limonoids, named carapanolides J–L (compounds 1–3) as well as a known gedunin-type limonoid 4 were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D and [...] Read more.

A novel gedunin and two novel phragmalin-type limonoids, named carapanolides J–L (compounds 1–3) as well as a known gedunin-type limonoid 4 were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D and 2D NMR spectroscopy and HRFABMS. Compounds 1–4 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. Full article

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Open AccessArticle

Anti-Inflammatory Potential of Newly Synthesized 4-[(Butylsulfinyl)methyl]-1,2-benzenediol in Lipopolysaccharide-Stimulated BV2 Microglia

by Guk-Heui Jo, Il-Whan Choi, Jin-Woo Jeong, Gi-Young Kim, Jinwoo Kim, Hongsuk Suh, Chung-Ho Ryu, Wun-Jae Kim and Yung Hyun Choi

Molecules 2014, 19(10), 16609-16623; https://doi.org/10.3390/molecules191016609 - 15 Oct 2014

Cited by 5 | Viewed by 7686

Abstract

In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) was detected in [...] Read more.

In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) was detected in BV2 cells; however, SMBD pretreatment inhibited the production of NO and PGE₂through suppressing gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, at non-toxic concentrations. LPS-stimulated gene expression and production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were also significantly reduced by SMBD. The anti-inflammatory effects of SMBD were associated with suppression of LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), and phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a phosphatidylinositol 3-kinase (PI3K) downstream effector. Therefore, the present results demonstrate that SMBD down-regulates inflammatory gene expression by inhibiting the activation of NF-κB through interference with the activation of MAPKs and PI3K/Akt signaling. Taken together, our data suggest that SMBD may have potential to be developed into an effective anti-inflammatory agent. Full article

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Open AccessArticle

Effects of Croton rhamnifolioides Essential Oil on Aedes aegypti Oviposition, Larval Toxicity and Trypsin Activity

by Geanne K. N. Santos, Kamilla A. Dutra, Camila S. Lira, Bheatriz N. Lima, Thiago H. Napoleão, Patrícia M. G. Paiva, Claudia A. Maranhão, Sofia S. F. Brandão and Daniela M. A. F. Navarro

Molecules 2014, 19(10), 16573-16587; https://doi.org/10.3390/molecules191016573 - 14 Oct 2014

Cited by 50 | Viewed by 9161

Abstract

Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its [...] Read more.

Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC₅₀ values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL⁻¹. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme. Full article

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Open AccessArticle

The Anthraquinone Derivatives from the Fungus Alternaria sp. XZSBG-1 from the Saline Lake in Bange, Tibet, China

by Bin Chen, Qiong Shen, Xun Zhu and Yongcheng Lin

Molecules 2014, 19(10), 16529-16542; https://doi.org/10.3390/molecules191016529 - 14 Oct 2014

Cited by 15 | Viewed by 6766

Abstract

Four new anthraquinone derivatives 1–4 were obtained along with seven known compounds 5–11 from the extracts of the fungal strain Alternaria sp. XZSBG-1 which was isolated from the sediments of the carbonate saline lake in Bange, Tibet, China. [...] Read more.

Four new anthraquinone derivatives 1–4 were obtained along with seven known compounds 5–11 from the extracts of the fungal strain Alternaria sp. XZSBG-1 which was isolated from the sediments of the carbonate saline lake in Bange, Tibet, China. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectra. Compound 1 is a novel tetrahydroanthraquinone with an epoxy ether bond between C-4a and C-9a. In the primary bioassays, compound 3 (alterporriol T) exhibited inhibition of a-glucosidase with a IC₅₀ value 7.2 μM, and compound 9 showed good inhibitory activity against the HCT-116 and HeLa cell lines, with IC₅₀ values of 3.03 and 8.09 μM, respectively. Full article

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Open AccessArticle

Stumps of Eucalyptus globulus as a Source of Antioxidant and Antimicrobial Polyphenols

by Ângelo Luís, Duarte Neiva, Helena Pereira, Jorge Gominho, Fernanda Domingues and Ana Paula Duarte

Molecules 2014, 19(10), 16428-16446; https://doi.org/10.3390/molecules191016428 - 13 Oct 2014

Cited by 70 | Viewed by 8354

Abstract

These past years have seen an enormous development of the area of natural antioxidants and antimicrobials. Eucalyptus globulus is widely cultivated in subtropical and Mediterranean regions in intensive short rotation coppice plantations. In the Portuguese context, E. globulus is the third species in [...] Read more.

These past years have seen an enormous development of the area of natural antioxidants and antimicrobials. Eucalyptus globulus is widely cultivated in subtropical and Mediterranean regions in intensive short rotation coppice plantations. In the Portuguese context, E. globulus is the third species in terms of forest area. The stump is the basal part of the tree, including the near-the-ground stem portion and the woody roots that remain after stem felling. The purpose of this work was to study the phytochemical profile and to evaluate the antioxidant and antimicrobial properties of several crude stump wood and stump bark extracts of E. globulus, comparing it with similar extracts of E. globulus wood (industrial chips). The results showed the presence of high concentrations of total phenolic compounds (>200 mg GAE/g extract) and flavonoids (>10 mg QE/g extract) in E. globulus stump extracts. Generally the stump wood extracts stands out from the other ones, presenting the highest percentages of inhibition of linoleic acid oxidation. It was also possible to conclude that the extracts were more active against Gram-positive bacteria, presenting low MIC values. This study thus provides information supporting the economic valorization of E. globulus stump wood. Full article

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Open AccessReview

Synthetic Advances in Macrosphelides: Natural Anticancer Agents

by Seung-Mann Paek

Molecules 2014, 19(10), 15982-16000; https://doi.org/10.3390/molecules191015982 - 8 Oct 2014

Cited by 7 | Viewed by 8940

Abstract

Total synthesis of macrosphelides is summarized. Synthetic approaches contain the preparation of key fragments and the final ring-closure reaction for unique 16- or 15-membered macrolactone skeletons. Full article

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Open AccessArticle

Effect Analysis of Mineral Salt Concentrations on Nosiheptide Production by Streptomyces actuosus Z-10 Using Response Surface Methodology

by Wei Zhou, Xiaohui Liu, Pei Zhang, Pei Zhou and Xunlong Shi

Molecules 2014, 19(10), 15507-15520; https://doi.org/10.3390/molecules191015507 - 26 Sep 2014

Cited by 10 | Viewed by 6572

Abstract

The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The [...] Read more.

The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The results showed that among the no-significant factors, CaCO₃, and K₂HPO₄·3H₂O had positive effects, whereas FeSO₄·7H₂O, CuSO₄·5H₂O, and ZnSO₄·7H₂O had negative effects on Nsh production. The other three significant factors (Na₂SO₄, MnSO₄·H₂O, and MgSO₄·7H₂O) were further optimized by using a five-level three-factor central composite design (CCD). Experimental data were fitted to a quadratic polynomial model, which provided an effective way to determine the interactive effect of metal salts on Nsh production. The optimal values were determined to be 2.63, 0.21, and 3.37 g/L, respectively. The model also ensured a good fitting of scale-up Nsh batch fermentation with a maximum production of 1501 mg/L, representing a 1.56-fold increase compared to the original standard condition. All these results revealed that statistical optimization methodology had the potential to achieve comprehensive optimization in Nsh fermentation behaviors, which indicates a possibility to establish economical large-scale production of Nsh. Full article

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Open AccessArticle

Identification of Three Elicitins and a Galactan-Based Complex Polysaccharide from a Concentrated Culture Filtrate of Phytophthora infestans Efficient against Pectobacterium atrosepticum

by Guillaume Saubeau, Fanny Gaillard, Laurent Legentil, Caroline Nugier-Chauvin, Vincent Ferrières, Didier Andrivon and Florence Val

Molecules 2014, 19(10), 15374-15390; https://doi.org/10.3390/molecules191015374 - 26 Sep 2014

Cited by 16 | Viewed by 9493

Abstract

The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense [...] Read more.

The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense responses and decrease the severity of soft rot due to Pectobacterium atrosepticum in potato tubers. The aim of this study was to identify and characterize the active compounds from P. infestans filtrate. The filtrate was fractionated by gel filtration, and the protection effects against P. atrosepticum and the ability to induce PAL activity were tested for each fraction. The fraction active in protection (F1) also induced PAL activity, as did the whole filtrate. Three elicitins (INF1, INF4 and INF5) were identified in F1b, subfraction of F1, by MALDI-TOF-MS and MS/MS analyses. However, deproteinized F1b still showed biological activity against the bacterium, revealing the presence of an additional active compound. GC-MS analyses of the deproteinized fraction highlighted the presence of a galactan-based complex polysaccharide. These experiments demonstrate that the biological activity of the CCF against P. atrosepticum results from a combined action of three elicitins and a complex polysaccharide, probably through the activation of general defense responses. Full article

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Open AccessArticle

LC-ESI-MS/MS Analysis and Pharmacokinetics of Plantainoside D Isolated from Chirita longgangensis var. hongyao, a Potential Anti-Hypertensive Active Component in Rats

by Manyuan Wang, Shujun Fu, Xinshi Zhang, Jing Li, Muxin Gong and Feng Qiu

Molecules 2014, 19(9), 15103-15115; https://doi.org/10.3390/molecules190915103 - 22 Sep 2014

Cited by 12 | Viewed by 7341

Abstract

Plantainoside D (PD) is a potential anti-hypertensive active ingredient newly isolated from the dried plants of Chirita longgangensis var. hongyao. A sensitive and specific LC-ESI-MS/MS method was first developed and validated for the analysis of PD in rat plasma using genistein as [...] Read more.

Plantainoside D (PD) is a potential anti-hypertensive active ingredient newly isolated from the dried plants of Chirita longgangensis var. hongyao. A sensitive and specific LC-ESI-MS/MS method was first developed and validated for the analysis of PD in rat plasma using genistein as the internal standard (IS). The plasma samples were pretreated with methanol-acetonitrile (50:50, v/v) to precipitate protein, and then chromatographed on a reverse-phase Agilent Zorbax XDB C18 column (50 mm × 2.1 mm, 3.5 μm). Gradient elution was utilized, with a mobile phase consisting of water and acetonitrile both containing 0.1% formic acid, and the flow rate was set at 0.50 mL/min. The analytes were monitored by tandem-mass spectrometry with negative electrospray ionization. The precursor/product transitions (m/z) in the negative ion mode were 639.2 → 160.9 Thomson (Th) and 268.9 → 158.9 Thomson (Th) for PD and IS, respectively. Linearity was achieved in the 0.10–200 ng/mL range, with a lower limit of quantification of 0.10 ng/mL. The precision and accuracy for both intra- and inter-day determination of the analyte were all within ±15%. The present method has been applied for pharmacokinetic study of PD after oral and intravenous administration in rats. The oral absolute bioavailability (F) of PD in rats was estimated to be 1.12% ± 0.46% with an elimination half-life (t_1/2) value of 1.63 ± 0.19 h, suggesting its poor absorption and/or strong metabolism in vivo. Full article

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Open AccessArticle

Tocotrienol-Rich Fraction, [6]-Gingerol and Epigallocatechin Gallate Inhibit Proliferation and Induce Apoptosis of Glioma Cancer Cells

by Amirah Abdul Rahman, Suzana Makpol, Rahman Jamal, Roslan Harun, Norfilza Mokhtar and Wan Zurinah Wan Ngah

Molecules 2014, 19(9), 14528-14541; https://doi.org/10.3390/molecules190914528 - 12 Sep 2014

Cited by 32 | Viewed by 9145

Abstract

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma [...] Read more.

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles. Full article

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Open AccessArticle

Constituents of the Roots and Leaves of Ekebergia capensis and Their Potential Antiplasmodial and Cytotoxic Activities

by Beatrice N. Irungu, Jennifer A. Orwa, Amra Gruhonjic, Paul A. Fitzpatrick, Göran Landberg, Francis Kimani, Jacob Midiwo, Máté Erdélyi and Abiy Yenesew

Molecules 2014, 19(9), 14235-14246; https://doi.org/10.3390/molecules190914235 - 10 Sep 2014

Cited by 34 | Viewed by 9286

Abstract

A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known triterpenoids 2–7 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 9–10 were found in its leaves. The [...] Read more.

A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known triterpenoids 2–7 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 9–10 were found in its leaves. The metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC₅₀’s of 1.4 and 13.3 µM against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 3–7 were evaluated on vero cells. In an antiplasmodial assay, seven of the metabolites were observed to possess moderate activity against the D6 and W2 strains of P. falciparum (IC₅₀ 27.1–97.1 µM), however with a low selectivity index (IC₅₀(vero)/IC₅₀(P. falciparum-D6) < 10). The observed moderate antiplasmodial activity may be due to general cytotoxicity of the isolated triterpenoids. Full article

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Open AccessArticle

Development of a Calcium Phosphate Nanocomposite for Fast Fluorogenic Detection of Bacteria

by Claudio R. Martínez, Tamara L. Rodríguez, Raisa Zhurbenko, Ivonne A. Valdés, Sávio M. L. Gontijo, Alinne D. M. Gomes, Diego F. Suarez, Rubén D. Sinisterra and Maria E. Cortés

Molecules 2014, 19(9), 13948-13964; https://doi.org/10.3390/molecules190913948 - 5 Sep 2014

Cited by 5 | Viewed by 6647

Abstract

Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a [...] Read more.

Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a nutritive mixture and the fluorogenic substrate. Calcium phosphate ceramic nanoparticles were characterized and integrated with a nutritive mixture for the early detection of bacteria by visual as well as fluorescence spectroscopy techniques. The composite was obtained by combining calcium phosphate nanoparticles (Ca:P ratio, 1.33:1) with a nutritive mixture of protein hydrolysates and carbon sources, which promote fast bacterial multiplication, and the fluorogenic substrate 4-methylumbellipheryl-β-d-glucuronide (MUG). The composite had an average particle size of 173.2 nm and did not show antibacterial activity against Gram-negative or Gram-positive bacteria. After an Escherichia coli suspension was in contact with the composite for 60–90 min, fluorescence detected under UV light or by fluorescence spectrophotometer indicated the presence of bacteria. Intense fluorescence was observed after incubation for a maximum of 90 min. Thus, this calcium phosphate nanocomposite system may be useful as a model for the development of other nanoparticle composites for detection of early bacterial adhesion. Full article

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Cytotoxic Compounds Isolated from Murraya tetramera Huang

by Chun-Xue You, Kai Yang, Cheng-Fang Wang, Wen-Juan Zhang, Ying Wang, Jiao Han, Li Fan, Shu-Shan Du, Zhu-Feng Geng and Zhi-Wei Deng

Molecules 2014, 19(9), 13225-13234; https://doi.org/10.3390/molecules190913225 - 27 Aug 2014

Cited by 25 | Viewed by 7266

Abstract

A new compound and seven known compounds were isolated from Murraya tetramera Huang for the first time, and they were identified with NMR and MS spectral analysis. It was confirmed that the new compound was 10-methoxy-7-methyl-2H-benzo[g]chromen-2-one (3) and the [...] Read more.

A new compound and seven known compounds were isolated from Murraya tetramera Huang for the first time, and they were identified with NMR and MS spectral analysis. It was confirmed that the new compound was 10-methoxy-7-methyl-2H-benzo[g]chromen-2-one (3) and the others were β-eudesmol (1), trans-3β-(1-hydroxy-1-methylethyl)-8aβ-methyl-5-methylenedecalin-2-one (2), 5,7-dimethoxy-8-[(Z)-3'-methyl-butan-1',3'-dienyl]coumarin (4), 7-geranyloxy-6-methoxycoumarin (5), 5,7-dimethoxy-8-(3-methyl-2-oxo-butyl)coumarin (6), murrangatin acetate (7) and toddalenone (8). Furthermore, the cytotoxic activity against human lung adenocarcinoma (A549), human hepatocellular carcinoma cells (SMMC-7721), human bladder tumor cells (EJ), human cervical carcinoma cells (HeLa), and human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1) was evaluated for all compounds. It was found that five of them displayed various degrees of cytotoxicity against different testing targets. Compound 1 showed significant cytotoxic activity against the five cell lines (A549, SMMC-7721, EJ, Hela and BALL-1). Compounds 2 and 5 showed significant cytotoxicity against three cell lines (A549, SMMC-7721 and BALL-1). Compound 4 showed significant cytotoxicity against three cell lines (A549, EJ and BALL-1). However, compound 3 only showed fair cytotoxicity against the BALL-1 cell line. The structure-active relationships were investigated as well. These active compounds might be potential lead compounds for the treatment of cancer. Full article

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Open AccessArticle

Isolation and Characterization of an α-Glucosidase Inhibitor from Musa spp. (Baxijiao) Flowers

by Zhanwu Sheng, Haofu Dai, Siyi Pan, Hui Wang, Yingying Hu and Weihong Ma

Molecules 2014, 19(7), 10563-10573; https://doi.org/10.3390/molecules190710563 - 18 Jul 2014

Cited by 61 | Viewed by 9701

Abstract

The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified [...] Read more.

The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao). Using NMR spectroscopy analysis they were identified as vanillic acid (1), ferulic acid (2), β-sitosterol (3), daucosterol (4) and 9-(4′-hydroxyphenyl)-2-methoxyphenalen-1-one (5). The half maximal inhibitory concentration (IC₅₀) values of compounds 1–5 were 2004.58, 1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known α-glucosidase inhibitor (acarbose, IC₅₀ = 999.31 mg/L), compounds 3, 4 and 5 showed a strong α-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are competitive inhibitors. The inhibition constants (K_i) of compounds 3, 4 and 5 were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show that the compounds 3, 4 and 5 are potent α-glucosidase inhibitors. Full article

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Open AccessArticle

Variation in the Bioactive Compound Content at Three Ripening Stages of Strawberry Fruit

by Sandra Voća, Jana Šic Žlabur, Nadica Dobričević, Lidija Jakobek, Marijan Šeruga, Ante Galić and Stjepan Pliestić

Molecules 2014, 19(7), 10370-10385; https://doi.org/10.3390/molecules190710370 - 17 Jul 2014

Cited by 29 | Viewed by 6814

Abstract

During the harvest season of two consecutive years, five strawberry cultivars (‘Arosa’, ‘Elsanta’, ‘Marmolada’, ‘Miss’ and ‘Raurica’), grown in the continental part of the Republic of Croatia, were examined. Strawberry fruits quality was evaluated by individual phenol compounds, individual anthocyanins and fruit color. [...] Read more.

During the harvest season of two consecutive years, five strawberry cultivars (‘Arosa’, ‘Elsanta’, ‘Marmolada’, ‘Miss’ and ‘Raurica’), grown in the continental part of the Republic of Croatia, were examined. Strawberry fruits quality was evaluated by individual phenol compounds, individual anthocyanins and fruit color. Fruits were harvested in three different periods. Analyzed strawberry cultivars show very good average values of the studied phenolic acids and flavonoids with predominant caffeic acid and epicatechin content in all researched strawberry cultivars. Considering the content of individual anthocyanins, pelargonidin 3-glucoside is predominant in strawberry extract followed by cyanidin-3-glucoside and pelargonidin 3-rutinoside. The correlation between individual anthocyanin content and chromaticity parameters was detected in all strawberry cultivars, additionally correlation coefficients and statistical significance were much lower. The results show a positive association between cultivar and harvest time on strawberry pulp color, with each of the color variables, a, b, a/b ratio, C, L and h° values. Full article

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Avicequinone C Isolated from Avicennia marina Exhibits 5α-Reductase-Type 1 Inhibitory Activity Using an Androgenic Alopecia Relevant Cell-Based Assay System

by Ruchy Jain, Orawan Monthakantirat, Parkpoom Tengamnuay and Wanchai De-Eknamkul

Molecules 2014, 19(5), 6809-6821; https://doi.org/10.3390/molecules19056809 - 23 May 2014

Cited by 27 | Viewed by 11402

Abstract

Avicennia marina (AM) exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5α-reductase (5α-R) [E.C.1.3.99.5], the enzyme responsible for the over-production of [...] Read more.

Avicennia marina (AM) exhibits various biological activities and has been traditionally used in Egypt to cure skin diseases. In this study, the methanolic heartwood extract of AM was evaluated for inhibitory activity against 5α-reductase (5α-R) [E.C.1.3.99.5], the enzyme responsible for the over-production of 5α-dihydrotestosterone (5α-DHT) causing androgenic alopecia (AGA). An AGA-relevant cell-based assay was developed using human hair dermal papilla cells (HHDPCs), the main regulator of hair growth and the only cells within the hair follicle that are the direct site of 5α-DHT action, combined with a non-radioactive thin layer chromatography (TLC) detection technique. The results revealed that AM is a potent 5α-R type 1 (5α-R1) inhibitor, reducing the 5α-DHT production by 52% at the final concentration of 10 µg/mL. Activity-guided fractionation has led to the identification of avicequinone C, a furanonaphthaquinone, as a 5α-R1 inhibitor with an IC₅₀ of 9.94 ± 0.33 µg/mL or 38.8 ± 1.29 µM. This paper is the first to report anti-androgenic activity through 5α-R1 inhibition of AM and avicequinone C. Full article

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Synthesis of Silver Nanoparticles by Green Method Stabilized to Synthetic Human Stomach Fluid

by Ayman M. Atta, Hamad A. Al-Lohedan and Abdelrahman O. Ezzat

Molecules 2014, 19(5), 6737-6753; https://doi.org/10.3390/molecules19056737 - 23 May 2014

Cited by 36 | Viewed by 9992

Abstract

Silver nanoparticles (Ag NP) have been attracted much attention in recent years in biomedical applications due to their antimicrobial activity, but their drawbacks include toxicity and instability to aqueous hydrochloric acid solutions. Ag NPs have now been successfully prepared by a simple and [...] Read more.

Silver nanoparticles (Ag NP) have been attracted much attention in recent years in biomedical applications due to their antimicrobial activity, but their drawbacks include toxicity and instability to aqueous hydrochloric acid solutions. Ag NPs have now been successfully prepared by a simple and “green” synthesis method by reducing Ag⁺ ions in the presence of modified poly(vinyl alcohol) thiol (PVA-SH) in aqueous acidic solution. In this respect, Ag NPs were stabilized by coating different types of citrate-reduced Ag NPs with different weight ratios (1–3 Wt. %) of PVSH derivatives. The as-prepared Ag NPs were characterized using UV-Visible, high resolution transmission electron microscopy/ energy dispersive X-ray spectroscopy (TEM/EDS), dynamic light scattering (DLS) and X-ray powder diffraction (XRD) combined with Rietveld analysis. The changes in size, shape, and hydrodynamic diameter of Ag NPs after different duration exposure to synthetic stomach fluid (SSF) and1 M HCl were determined using TEM, XRD and UV-Visible analyses. The data indicated that these Ag NPs possessed high stability to SSF for more than 90 days, which was not previously reported in the literature. Full article

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Open AccessArticle

Evaluation of Antioxidant Activity, Polyphenolic Compounds, Amino Acids and Mineral Elements of Representative Genotypes of Lonicera edulis

by Jiri Sochor, Tunde Jurikova, Miroslav Pohanka, Helena Skutkova, Mojmir Baron, Lenka Tomaskova, Stefan Balla, Borivoj Klejdus, Robert Pokluda, Jiri Mlcek, Zuzana Trojakova and Jan Saloun

Molecules 2014, 19(5), 6504-6523; https://doi.org/10.3390/molecules19056504 - 21 May 2014

Cited by 24 | Viewed by 10804

Abstract

The aim of this study was to evaluate the bioactive substances in 19 berry cultivars of edible honeysuckle (Lonicera edulis). A statistical evaluation was used to determine the relationship between the content of selected bioactive substances and individual cultivars. Regarding mineral [...] Read more.

The aim of this study was to evaluate the bioactive substances in 19 berry cultivars of edible honeysuckle (Lonicera edulis). A statistical evaluation was used to determine the relationship between the content of selected bioactive substances and individual cultivars. Regarding mineral elements, the content of sodium was measured using potentiometry and spectrophotometry. The content of selected polyphenolic compounds with high antioxidant activity was determined by a HPLC–UV/ED method. The total amount of polyphenols was determined by the Folin-Ciocalteu method. The antioxidant activity was determined using five methods (DPPH, FRAP, ABTS, FR and DMPD) that differ in their principles. The content of 13 amino acids was determined by ion-exchange chromatography. The experimental results obtained for the different cultivars were evaluated and compared by statistical and bioinformatic methods. A unique feature of this study lies in the exhaustive analysis of the chosen parameters (amino acids, mineral elements, polyphenolic compounds and antioxidant activity) during one growing season. Full article

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Fucoidan Inhibits the Proliferation of Human Urinary Bladder Cancer T24 Cells by Blocking Cell Cycle Progression and Inducing Apoptosis

by Hye Young Park, Gi-Young Kim, Sung-Kwon Moon, Wun Jae Kim, Young Hyun Yoo and Yung Hyun Choi

Molecules 2014, 19(5), 5981-5998; https://doi.org/10.3390/molecules19055981 - 9 May 2014

Cited by 62 | Viewed by 12138

Abstract

Although fucoidan has been shown to exert anticancer activity against several types of cancer cell lines, no reports have explored fucoidan-affected cell growth in human urinary bladder cancer cells. In this study, we investigated the anti-proliferative effects of fucoidan in human bladder cancer [...] Read more.

Although fucoidan has been shown to exert anticancer activity against several types of cancer cell lines, no reports have explored fucoidan-affected cell growth in human urinary bladder cancer cells. In this study, we investigated the anti-proliferative effects of fucoidan in human bladder cancer T24 cells. Our results indicated that fucoidan decreased the viability of T24 cells through the induction of G1 arrest and apoptosis. Fucoidan-induced G1 arrest is associated with the enhanced expression of the Cdk inhibitor p21WAF1/CIP1 and dephosphorylation of the pRB along with enhanced binding of p21 to Cdk4/6 as well as pRB to the transcription factor E2Fs. Further investigations showed the loss of mitochondrial membrane potential and the release of cytochrome c from mitochondria to cytosol, proving mitochondrial dysfunction upon fucoidan treatment with a corresponding increase in the Bax/Bcl-2 expression ratio. Fucoidan-triggered apoptosis was also accompanied by the up-regulation of Fas and truncated Bid as well as the sequential activation of caspase-8. Furthermore, a significant increased activation of caspase-9/-3 was detected in response to fucoidan treatment with the decreased expression of IAPs and degradation of PARP, whereas a pan-caspase inhibitor significantly suppressed apoptosis and rescued the cell viability reduction. In conclusion, these observations suggest that fucoidan attenuates G1-S phase cell cycle progression and serves as an important mediator of crosstalk between caspase-dependent intrinsic and extrinsic apoptotic pathways in T24 cells. Full article

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Open AccessArticle

Five New Alkaloids from the Stem Bark of Daphniphyllum macropodum

by Yunyang Lu, Kai Gao, Xiaoyang Wang, Wei Zhang, Ning Ma and Haifeng Tang

Molecules 2014, 19(3), 3055-3067; https://doi.org/10.3390/molecules19033055 - 10 Mar 2014

Cited by 13 | Viewed by 7616

Abstract

Five new alkaloids, daphnicyclidins M and N (compounds 1 and 2) and calyciphyllines Q–S (compounds 3–5), along with four known ones, paxiphylline C (6), macropodumine B (7), macropodumine C (8) and daphnicyclidin A [...] Read more.

Five new alkaloids, daphnicyclidins M and N (compounds 1 and 2) and calyciphyllines Q–S (compounds 3–5), along with four known ones, paxiphylline C (6), macropodumine B (7), macropodumine C (8) and daphnicyclidin A (9) were isolated from the stem bark of Daphniphyllum macropodum. Calyciphylline Q (3) is the first calyciphylline A derivative possessing a double bond between C-18 and C-19. Their structures and relative configurations were elucidated on the basis of spectroscopic methods, especially 2D NMR techniques. Compounds 1, 2, 8 and 9 exhibited cytotoxic activity against P-388 cells with IC₅₀ values of 5.7, 6.5, 10.3 and 13.8 µM, respectively. Compounds 1 and 2 also showed cytotoxic activity against SGC-7901 cells with IC₅₀ values of 22.4 and 25.6 µM. Full article

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Open AccessArticle

Unravelling the Complex Antimicrobial Interactions of Essential Oils — The Case of Thymus vulgaris (Thyme)

by Aijaz Ahmad, Sandy Van Vuuren and Alvaro Viljoen

Molecules 2014, 19(3), 2896-2910; https://doi.org/10.3390/molecules19032896 - 6 Mar 2014

Cited by 65 | Viewed by 12246

Abstract

Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO) [...] Read more.

Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb and its use in phytotherapy is well established and supported in the literature. The objective of this study was to explore possible interactions between selected molecules within Thymus vulgaris essential oil (TvEO) to gain a better understanding of how this complex essential oil exerts its antimicrobial activity. Evaluation of the antimicrobial efficacy and interactions were assessed on the essential oil and volatile constituents against various pathogens. Interactions between molecules at various ratios were graphically observed through the construction of isobolograms. Gas chromatography-mass spectrometry (GC-MS) analysis revealed 22 compounds which collectively represent >95% of the oil composition. Based on their minimum inhibitory concentration (MIC) values, they were categorised into weak (≥4 mg mL⁻¹), moderate (2–4 mg mL⁻¹) and noteworthy active (≤2 mg mL⁻¹) compounds. For the combination study, 21% synergistic, 42% additive, 36% indifferent and 1% antagonistic interactions were observed. Most of the interactions were observed between the weak and highly active molecules, and interestingly, no synergistic interaction was observed between the highly active compounds. Synergistic and additive interactions between the strong and weaker antimicrobial constituents present in TvEO enhance the antimicrobial efficacy of this commercially important essential oil. Full article

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Cytotoxic Oleanane-Type Triterpenoid Saponins from the Rhizomes of Anemone rivularis var. flore-minore

by Xiaoyang Wang, Minchang Wang, Min Xu, Yi Wang, Haifeng Tang and Xiaoli Sun

Molecules 2014, 19(2), 2121-2134; https://doi.org/10.3390/molecules19022121 - 18 Feb 2014

Cited by 17 | Viewed by 7669

Abstract

Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone rivularis var. flore-minore led to the isolation of five new oleanane-type triterpenoid saponins 1–5, together with five known saponins 6–10. Their structures were determined by [...] Read more.

Phytochemical investigation of the n-BuOH extract of the rhizomes of Anemone rivularis var. flore-minore led to the isolation of five new oleanane-type triterpenoid saponins 1–5, together with five known saponins 6–10. Their structures were determined by the extensive use of 1D and 2D NMR experiments, along with ESIMS analyses and acid hydrolysis. The aglycone of 4 and 5 was determined as 21α-hydroxyoleanolic acid, which was reported in this genus for the first time. The cytotoxicity of these compounds was evaluated against four human cancer cell line, including HL-60 (promyelocytic leukemia), HepG2 (hepatocellular carcinoma), A549 (lung carcinoma) and HeLa (cervical carcinoma). The monodesmosidic saponins 6–8 exhibited cytotoxic activity toward all tested cancer cell lines, with IC₅₀ values in the 7.25–22.38 μM range. Full article

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Open AccessArticle

Docking Studies in Target Proteins Involved in Antibacterial Action Mechanisms: Extending the Knowledge on Standard Antibiotics to Antimicrobial Mushroom Compounds

by Maria José Alves, Hugo J. C. Froufe, Ana F. T. Costa, Anabela F. Santos, Liliana G. Oliveira, Sara R. M. Osório, Rui M. V. Abreu, Manuela Pintado and Isabel C. F. R. Ferreira

Molecules 2014, 19(2), 1672-1684; https://doi.org/10.3390/molecules19021672 - 29 Jan 2014

Cited by 61 | Viewed by 12114

Abstract

In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different [...] Read more.

In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), d-alanyl-d-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets. Full article

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2013

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Open AccessArticle

Bioactive Compounds from the Roots of Asiasarum heterotropoides

by Jun Lee, You Jin Lee, Se-Mi Oh, Jin-Mu Yi, No Soo Kim and Ok-Sun Bang

Molecules 2014, 19(1), 122-138; https://doi.org/10.3390/molecules19010122 - 23 Dec 2013

Cited by 17 | Viewed by 8543

Abstract

A new tetrahydrofuran lignan, (7S,8R,7'S,8'S)-3-methoxy-3',4'-methylenedioxy-7,9'-epoxylignane-4,7',9-triol (1), and 21 known compounds 2–22 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 1–22 [...] Read more.

A new tetrahydrofuran lignan, (7S,8R,7'S,8'S)-3-methoxy-3',4'-methylenedioxy-7,9'-epoxylignane-4,7',9-triol (1), and 21 known compounds 2–22 were isolated from the roots of Asiasarum heterotropoides by chromatographic separation methods. The structures of all compounds 1–22 were elucidated by spectroscopic analysis including 1D- and 2D-NMR. Fourteen of these compounds (1–3, 7, 10, 12–17, 19, 21, and 22) were isolated from this species in this study for the first time. All of the isolates were evaluated for their anticancer activities using in vitro assays. Among the 22 tested compounds, two (compounds 5 and 7) induced the downregulation of NO production, FOXP3 expression, and HIF-1α transcriptional activity. Full article

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Open AccessArticle

Optimized Ultrasound-Assisted Extraction of Phenolic Compounds from Polygonum cuspidatum

by Chia-Hung Kuo, Bao-Yuan Chen, Yung-Chuan Liu, Chieh-Ming J. Chang, Tzu-Shing Deng, Jiann-Hwa Chen and Chwen-Jen Shieh

Molecules 2014, 19(1), 67-77; https://doi.org/10.3390/molecules19010067 - 20 Dec 2013

Cited by 45 | Viewed by 9349

Abstract

In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed [...] Read more.

In this study the phenolic compounds piceid, resveratrol and emodin were extracted from P. cuspidatum roots using ultrasound-assisted extraction. Multiple response surface methodology was used to optimize the extraction conditions of these phenolic compounds. A three-factor and three-level Box-Behnken experimental design was employed to evaluate the effects of the operation parameters, including extraction temperature (30–70 °C), ethanol concentration (40%–80%), and ultrasonic power (90–150 W), on the extraction yields of piceid, resveratrol, and emodin. The statistical models built from multiple response surface methodology were developed for the estimation of the extraction yields of multi-phenolic components. Based on the model, the extraction yields of piceid, resveratrol, and emodin can be improved by controlling the extraction parameters. Under the optimum conditions, the extraction yields of piceid, resveratrol and emodin were 10.77 mg/g, 3.82 mg/g and 11.72 mg/g, respectively. Full article

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Open AccessArticle

5-Episinuleptolide Acetate, a Norcembranoidal Diterpene from the Formosan Soft Coral Sinularia sp., Induces Leukemia Cell Apoptosis through Hsp90 Inhibition

by Kao-Jean Huang, Yu-Cheng Chen, Mohamed El-Shazly, Ying-Chi Du, Jui-Hsin Su, Chia-Wei Tsao, Wei-Hsuan Yen, Wen-Been Chang, Yin-Di Su, Yao-Tsung Yeh and Mei-Chin Lu

Molecules 2013, 18(3), 2924-2933; https://doi.org/10.3390/molecules18032924 - 4 Mar 2013

Cited by 24 | Viewed by 6641

Abstract

5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic [...] Read more.

5-Episinuleptolide acetate (5EPA), a cytotoxic norcembranoidal diterpene recently identified from the Formosan soft coral Sinularia sp., exhibited potent activity against the K562, Molt 4 and HL 60 cancer cell lines. The antiproliferative assay, as well as the annexin V-FITC/propidium iodide (PI) apoptotic assay, indicated that the HL 60 cell line is the most sensitive one towards 5EPA. This diterpenoid led to caspases -3, -8, and -9 activation as well as PARP cleavage. It also induced ROS generation, calcium accumulation and disruption of mitochondrial membrane potential. Additionally, the expression levels of Hsp90 protein and several client proteins were downregulated in response to 5EPA treatment. These results suggest that 5EPA’s cytotoxic effect on HL 60 cells may be attributed to the inhibition of Hsp90 as well as the induction of mitochondrial stress which finally results in apoptotic cell death. Full article

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2012

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Open AccessReview

Anti-Infectious Agents against MRSA

by Nobuhiro Koyama, Junji Inokoshi and Hiroshi Tomoda

Molecules 2013, 18(1), 204-224; https://doi.org/10.3390/molecules18010204 - 24 Dec 2012

Cited by 50 | Viewed by 9930

Abstract

Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA) has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, [...] Read more.

Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA) has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652) targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP) synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described. Full article

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Open AccessReview

Action of Natural Products on P2 Receptors: A Reinvented Era for Drug Discovery

by Robson Faria, Leonardo Ferreira, Rômulo Bezerra, Valber Frutuoso and Luiz Alves

Molecules 2012, 17(11), 13009-13025; https://doi.org/10.3390/molecules171113009 - 1 Nov 2012

Cited by 21 | Viewed by 10175

Abstract

Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With [...] Read more.

Natural products contribute significantly to available drug therapies and have been a rich source for scientific investigation. In general, due to their low cost and traditional use in some cultures, they are an object of growing interest as alternatives to synthetic drugs. With several diseases such as cancer, and inflammatory and neuropathic diseases having been linked to the participation of purinergic (P2) receptors, there has been a flurry of investigations on ligands within natural products. Thirty-four different sources of these compounds have been found so far, that have shown either agonistic or antagonistic effects on P2 receptors. Of those, nine different plant sources demonstrated effects on P2X2, P2X3, P2X7, and possibly P2Y12 receptor subtypes. Microorganisms, which represent the largest group, with 26 different sources, showed effects on both receptor subtypes, ranging from P2X1 to P2X4 and P2X7, and P2Y1, P2Y2, P2Y4, and P2Y6. In addition, there were seventeen animal sources that affected P2X7 and P2Y1 and P2Y12 receptors. Natural products have provided some fascinating new mechanisms and sources to better understand the P2 receptor antagonism. Moreover, current investigations should clarify further pharmacological mechanisms in order to consider these products as potential new medicines. Full article

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Open AccessArticle

Synthetic Flavanones Augment the Anticancer Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)

by Ewelina Szliszka, Edyta Kostrzewa-Susłow, Joanna Bronikowska, Dagmara Jaworska, Tomasz Janeczko, Zenon P. Czuba and Wojciech Krol

Molecules 2012, 17(10), 11693-11711; https://doi.org/10.3390/molecules171011693 - 1 Oct 2012

Cited by 26 | Viewed by 7359

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, [...] Read more.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new therapeutic strategies to overcome this resistance. Flavonoids have been shown to sensitize cancer cells to TRAIL-induced apoptosis. The aim of this study was to examine the cytotoxic and apoptotic activities of TRAIL on HeLa cancer cells in combination with two synthetic compounds: 6-hydroxyflavanone (6-HF) and its derivative 6-propionoxy-flavanone (6-PF) and to determine the mechanism by which the flavanones overcome the TRAIL-resistance. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected by annexin V-FITC fluorescence staining in flow cytometry and microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression were analysed using flow cytometry. Mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. The synthetic flavanones enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and reduction of mitochondrial membrane potential. Our study indicates that the 6-HF and 6-PF augmented the anticancer effects of TRAIL and confirm a potential use of flavanones in TRAIL-based anticancer therapy and prevention. Full article

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Open AccessArticle

Effects of Sorghum [Sorghum bicolor (L.) Moench] Crude Extracts on Starch Digestibility, Estimated Glycemic Index (EGI), and Resistant Starch (RS) Contents of Porridges

by Dilek Lemlioglu-Austin, Nancy D. Turner, Cassandra M. McDonough and Lloyd W. Rooney

Molecules 2012, 17(9), 11124-11138; https://doi.org/10.3390/molecules170911124 - 17 Sep 2012

Cited by 76 | Viewed by 9799

Abstract

Bran extracts (70% aqueous acetone) of specialty sorghum varieties (tannin, black, and black with tannin) were used to investigate the effects of sorghum phenolic compounds on starch digestibility, Estimated Glycemic Index (EGI), and Resistant Starch (RS) of porridges made with normal corn starch, [...] Read more.

Bran extracts (70% aqueous acetone) of specialty sorghum varieties (tannin, black, and black with tannin) were used to investigate the effects of sorghum phenolic compounds on starch digestibility, Estimated Glycemic Index (EGI), and Resistant Starch (RS) of porridges made with normal corn starch, enzyme resistant high amylose corn starch, and ground whole sorghum flours. Porridges were cooked with bran extracts in a Rapid Visco-analyser (RVA). The cooking trials indicated that bran extracts of phenolic-rich sorghum varieties significantly reduced EGI, and increased RS contents of porridges. Thus, there could be potential health benefits associated with the incorporation of phenolic-rich sorghum bran extracts into foods to slow starch digestion and increase RS content. Full article

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Open AccessArticle

Protective Effects of the Key Compounds Isolated from Corni fructus against β-Amyloid-Induced Neurotoxicity in PC12 Cells

by Seung-Young Hong, Woo-Sik Jeong and Mira Jun

Molecules 2012, 17(9), 10831-10845; https://doi.org/10.3390/molecules170910831 - 10 Sep 2012

Cited by 68 | Viewed by 7917

Abstract

β-Amyloid (Aβ) peptide is the major component of senile plaques and is considered to have a causal role in the development and progression of Alzheimer’s disease (AD). There is compelling evidence supporting the notion that Aβ-induced cytotoxicity is mediated though the generation of [...] Read more.

β-Amyloid (Aβ) peptide is the major component of senile plaques and is considered to have a causal role in the development and progression of Alzheimer’s disease (AD). There is compelling evidence supporting the notion that Aβ-induced cytotoxicity is mediated though the generation of ROS. In the present study, we investigated the neuroprotective effects of ursolic acid (UA), p-coumaric acid (p-CA), and gallic acid (GA) isolated from Corni fructus (CF) against Aβ(25–35)-induced toxicity in PC12 cell. Exposure of PC12 cells to 50 μM Aβ(25–35) increased cellular oxidative stress, the number of apoptotic cells and caspase-3 activity and finally caused significant cell death. However, UA, p-CA, and GA not only suppressed the generation of ROS but also attenuated DNA fragmentation and eventually attenuated Aβ-induced apoptosis in a dose-dependent manner. In protecting cells against Aβ neurotoxicity, UA and GA possessed stronger ability against ROS generation than p-CA, while p-CA showed the strongest anti-apoptotic activity. Particularly, p-CA protected cells at the concentration range from 0.5 up to 125 μM without any adverse effect. Taken together, these effects of UA, p-CA, and GA may be partly associated with the neuroprotective effect of CF. Furthermore, our findings might raise a possibility of therapeutic applications of CF for preventing and/or treating neurodegenerative diseases. Full article

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Open AccessArticle

Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?

by Leena Pohjala and Päivi Tammela

Molecules 2012, 17(9), 10774-10790; https://doi.org/10.3390/molecules170910774 - 7 Sep 2012

Cited by 87 | Viewed by 7118

Abstract

Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, [...] Read more.

Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, concerning their aggregating tendency and the relevance of this phenomenon to obtaining false bioassay results. Fourteen compounds formed aggregates detectable by dynamic light scattering (DLS) when assayed at 10 µM in Tris-HCl pH 7.5. Flavonoids were more prone to aggregation than other phenolic compounds, and the aggregate formation was highly dependent on the vehicle, ionic strength and pH. The compounds were also assayed against three unrelated enzymes in the presence and absence of Triton X-100, and their bioactivity ratios were collected from PubChem database. By comparing these datasets, quercetin and rhamnetin were confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher bioactivity ratios in the PubChem database than coumarins or organic acids. To conclude, aggregate formation can be controlled with Triton X-100 and this phenomenon needs to be considered when bioassay data is interpreted, but our data indicates that it does not always lead to unspecific inhibition of biological targets. Full article

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Open AccessReview

Bioprospecting of Marine Invertebrates for New Natural Products — A Chemical and Zoogeographical Perspective

by Miguel Costa Leal, Carolina Madeira, Cláudio Alexandre Brandão, João Puga and Ricardo Calado

Molecules 2012, 17(8), 9842-9854; https://doi.org/10.3390/molecules17089842 - 16 Aug 2012

Cited by 58 | Viewed by 10965

Abstract

Bioprospecting for new marine natural products (NPs) has increased significantly over the last decades, leading to an unprecedented discovery of new molecules. Marine invertebrates have been the most important source of these NPs, with researchers commonly targeting particular taxonomic groups, marine regions and/or [...] Read more.

Bioprospecting for new marine natural products (NPs) has increased significantly over the last decades, leading to an unprecedented discovery of new molecules. Marine invertebrates have been the most important source of these NPs, with researchers commonly targeting particular taxonomic groups, marine regions and/or molecules from specific chemical groups. The present review focuses on new NPs identified from marine invertebrates between 2000 and 2009, and performs a detailed analysis on: (1) the chemical groups of these NPs; (2) the association of particular chemical groups to specific marine invertebrate taxa; and (3) the yielding of molecules from the same chemical group from organisms occurring in a particular geographic region. Our survey revealed an increasing number of new terpenoids being discovered between 2000 and 2009, contrasting with the decreasing trend in the discovery of new alkaloids and aliphatic molecules. Overall, no particular association was identified between marine invertebrate taxa and chemical groups of new NPs. Nonetheless, it is worth noting that most NPs recorded from cnidarians and mollusks were terpenoids, while most NPs identified in echinoderms were aliphatic compounds or carbohydrates. The geographical trends observed in our study do not support the idea of particular chemical groups of new NPs being associated with marine invertebrates from any specific geographical region, as NPs from different chemical groups were commonly distributed worldwide. Full article

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Open AccessArticle

Antifungal Activity, Toxicity and Chemical Composition of the Essential Oil of Coriandrum sativum L. Fruits

by Bruna V. Soares, Selene M. Morais, Raquel Oliveira Dos Santos Fontenelle, Vanessa A. Queiroz, Nadja S. Vila-Nova, Christiana M. C. Pereira, Edy S. Brito, Manoel A. S. Neto, Erika H. S. Brito, Carolina S. P. Cavalcante, Débora S. C. M. Castelo-Branco and Marcos F. G. Rocha

Molecules 2012, 17(7), 8439-8448; https://doi.org/10.3390/molecules17078439 - 11 Jul 2012

Cited by 54 | Viewed by 7929

Abstract

The aims of this study were to test the antifungal activity, toxicity and chemical composition of essential oil from C. sativum L. fruits. The essential oil, obtained by hydro-distillation, was analyzed by gas chromatography/mass spectroscopy. Linalool was the main constituent (58.22%). The oil [...] Read more.

The aims of this study were to test the antifungal activity, toxicity and chemical composition of essential oil from C. sativum L. fruits. The essential oil, obtained by hydro-distillation, was analyzed by gas chromatography/mass spectroscopy. Linalool was the main constituent (58.22%). The oil was considered bioactive, showing an LC₅₀ value of 23 µg/mL in the Artemia salina lethality test. The antifungal activity was evaluated against Microsporum canis and Candida spp. by the agar-well diffusion method and the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were established by the broth microdilution method. The essential oil induced growth inhibition zones of 28 ± 5.42 and 9.25 ± 0.5 for M. canis and Candida spp. respectively. The MICs and MFCs for M. canis strains ranged from 78 to 620 and 150 to 1,250 µg/mL, and the MICs and MFCs for Candida spp strains ranged from 310 to 620 and 620 to 1,250 µg/mL, respectively. C. sativum essential oil is active in vitro against M. canis and Candida spp. demonstrating good antifungal activity. Full article

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Open AccessArticle

Gamma-Mangostin, a Micronutrient of Mangosteen Fruit, Induces Apoptosis in Human Colon Cancer Cells

by Hui-Fang Chang and Ling-Ling Yang

Molecules 2012, 17(7), 8010-8021; https://doi.org/10.3390/molecules17078010 - 3 Jul 2012

Cited by 54 | Viewed by 9444

Abstract

Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (Garcinia mangostana) is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous [...] Read more.

Recently colorectal cancer rates have increased rapidly in Taiwan. The treatment of colorectal cancer includes surgery, radiation therapy and chemotherapy. Mangosteen (Garcinia mangostana) is a famous Asian tropical fruit. γ-Mangostin is a xanthone derivative isolated from the fruit hull. In previous studies, we found evidence of anti-inflammatory and anti-brain tumor activities in γ-mangostin. In this study, we performed further studies to assess the apoptotic effects of γ-mangostin on colorectal adenocarcinoma cells HT29. γ-Mangostin showed concentration and time-dependent cytotoxic effects on HT29 cells. Microscopic observation under Giemsa staining showed that γ-mangostin induced cellular swelling and the appearance of apoptotic bodies, characteristic of apoptosis in HT29 cells. In addition, flow cytometry analysis showed an increase of hypodiploid cells in γ-mangostin-treated HT29 cells, while enhancement of intracellular peroxide production was detected in the same γ-mangostin-treated cells by DCHDA assay and DiOC6(3) staining. In view of the above results, γ-mangostin has demonstrated anticancer activity and induces apoptosis in HT29 colorectal adenocarcinoma cells. The evidence suggests that γ-mangostin could serve as a micronutrient for colon cancer prevention and is a potential lead compound for the development of anti-colon cancer agents. Full article

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Open AccessReview

The Genus Caesalpinia L. (Caesalpiniaceae): Phytochemical and Pharmacological Characteristics

by João L. Baldim Zanin, Bianca A. De Carvalho, Paloma Salles Martineli, Marcelo Henrique Dos Santos, João Henrique G. Lago, Patrícia Sartorelli, Cláudio Viegas, Jr. and Marisi G. Soares

Molecules 2012, 17(7), 7887-7902; https://doi.org/10.3390/molecules17077887 - 29 Jun 2012

Cited by 95 | Viewed by 13564

Abstract

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. [...] Read more.

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia. Full article

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Open AccessArticle

Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents

by Dahong Li, Lei Wang, Hao Cai, Yihua Zhang and Jinyi Xu

Molecules 2012, 17(6), 7556-7568; https://doi.org/10.3390/molecules17067556 - 18 Jun 2012

Cited by 36 | Viewed by 7205

Abstract

To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives [...] Read more.

To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC₅₀ values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents. Full article

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Open AccessReview

Eugenol—From the Remote Maluku Islands to the International Market Place: A Review of a Remarkable and Versatile Molecule

by Guy P. Kamatou, Ilze Vermaak and Alvaro M. Viljoen

Molecules 2012, 17(6), 6953-6981; https://doi.org/10.3390/molecules17066953 - 6 Jun 2012

Cited by 398 | Viewed by 34913

Abstract

Eugenol is a major volatile constituent of clove essential oil obtained through hydrodistillation of mainly Eugenia caryophyllata (=Syzygium aromaticum) buds and leaves. It is a remarkably versatile molecule incorporated as a functional ingredient in numerous products and has found application in [...] Read more.

Eugenol is a major volatile constituent of clove essential oil obtained through hydrodistillation of mainly Eugenia caryophyllata (=Syzygium aromaticum) buds and leaves. It is a remarkably versatile molecule incorporated as a functional ingredient in numerous products and has found application in the pharmaceutical, agricultural, fragrance, flavour, cosmetic and various other industries. Its vast range of pharmacological activities has been well-researched and includes antimicrobial, anti-inflammatory, analgesic, anti-oxidant and anticancer activities, amongst others. In addition, it is widely used in agricultural applications to protect foods from micro-organisms during storage, which might have an effect on human health, and as a pesticide and fumigant. As a functional ingredient, it is included in many dental preparations and it has also been shown to enhance skin permeation of various drugs. Eugenol is considered safe as a food additive but due to the wide range of different applications, extensive use and availability of clove oil, it is pertinent to discuss the general toxicity with special reference to contact dermatitis. This review summarises the pharmacological, agricultural and other applications of eugenol with specific emphasis on mechanism of action as well as toxicity data. Full article

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Open AccessArticle

Improved Methods for Thermal Rearrangement of Alicyclic α-Hydroxyimines to α-Aminoketones: Synthesis of Ketamine Analogues as Antisepsis Candidates

by Hagit Elhawi, Hadar Eini, Amos Douvdevani and Gerardo Byk

Molecules 2012, 17(6), 6784-6807; https://doi.org/10.3390/molecules17066784 - 4 Jun 2012

Cited by 73 | Viewed by 10474

Abstract

Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low [...] Read more.

Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a rat model of Gram-negative bacterial-sepsis that if we inject a low dose of ketamine following bacterial inoculation we reduce mortality from approximately 75% to 25%. Similar to what we have observed in operated patients, the levels of TNF-α and IL-6 in ketamine-treated rats were significantly lower than in septic animals not treated with ketamine. On the base of these results, we have designed and synthesized series of new analogues of ketamine applying a thermal rearrangement of alicyclic α-hydroxyimines to a-aminoketones in parallel arrays. One of the analogues (compound 6e) displayed high activity in down-regulating the levels of IL-6 and TNF-α in vivo as compared to ketamine. Full article

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Open AccessReview

The Role of Bioactive Compounds on the Promotion of Neurite Outgrowth

by Sandeep Vasant More, Sushruta Koppula, In-Su Kim, Hemant Kumar, Byung-Wook Kim and Dong-Kug Choi

Molecules 2012, 17(6), 6728-6753; https://doi.org/10.3390/molecules17066728 - 4 Jun 2012

Cited by 68 | Viewed by 8747

Abstract

Neurite loss is one of the cardinal features of neuronal injury. Apart from neuroprotection, reorganization of the lost neuronal network in the injured brain is necessary for the restoration of normal physiological functions. Neuritogenic activity of endogenous molecules in the brain such as [...] Read more.

Neurite loss is one of the cardinal features of neuronal injury. Apart from neuroprotection, reorganization of the lost neuronal network in the injured brain is necessary for the restoration of normal physiological functions. Neuritogenic activity of endogenous molecules in the brain such as nerve growth factor is well documented and supported by scientific studies which show innumerable compounds having neurite outgrowth activity from natural sources. Since the damaged brain lacks the reconstructive capacity, more efforts in research are focused on the identification of compounds that promote the reformation of neuronal networks. An abundancy of natural resources along with the corresponding activity profiles have shown promising results in the field of neuroscience. Recently, importance has also been placed on understanding neurite formation by natural products in relation to neuronal injury. Arrays of natural herbal products having plentiful active constituents have been found to enhance neurite outgrowth. They act synergistically with neurotrophic factors to promote neuritogenesis in the diseased brain. Therefore use of natural products for neuroregeneration provides new insights in drug development for treating neuronal injury. In this study, various compounds from natural sources with potential neurite outgrowth activity are reviewed in experimental models. Full article

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Open AccessArticle

The Coumarin Psoralidin Enhances Anticancer Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)

by Joanna Bronikowska, Ewelina Szliszka, Dagmara Jaworska, Zenon P. Czuba and Wojciech Krol

Molecules 2012, 17(6), 6449-6464; https://doi.org/10.3390/molecules17066449 - 29 May 2012

Cited by 82 | Viewed by 8089

Abstract

Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells [...] Read more.

Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention. Full article

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Open AccessArticle

Biological Activities of a-Pinene and β-Pinene Enantiomers

by Ana Cristina Rivas da Silva, Paula Monteiro Lopes, Mariana Maria Barros de Azevedo, Danielle Cristina Machado Costa, Celuta Sales Alviano and Daniela Sales Alviano

Molecules 2012, 17(6), 6305-6316; https://doi.org/10.3390/molecules17066305 - 25 May 2012

Cited by 453 | Viewed by 28203

Abstract

The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal [...] Read more.

The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with MICs ranging from 117 to 4,150 µg/mL. However, no antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL. Time-kill curves showed that (+)-a-pinene and (+)-β-pinene were highly toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast, the bactericidal effect occurred after 6 h in methicillin-resistant Staphylococcus aureus (MRSA). In combination with commercial antimicrobials, ciprofloxacin plus (+)-a-pinene or (+)-β-pinene presented synergistic activity against MRSA whereas an indifferent effect against all fungi was detected when amphotericin B was combined with the positive enantiomers of pinene. The potential of (+)-a-pinene and (+)-β-pinene to inhibit phospholipase and esterase activities was also evaluated, and the best inhibition results were obtained with Cryptococcus neoformans. C. albicans biofilm formation was prevented with the MIC concentration of (+)-a-pinene and twice the MIC value of (+)-β-pinene. Finally, the cytotoxicity of the positive enantiomers of pinene to murine macrophages was evaluated, and 250 µg/mL of (+)-a-pinene and (+)-β-pinene reduced the cell viability to 66.8% and 57.7%, respectively. Full article

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Open AccessReview

Synthesis and Bioactivity of Secondary Metabolites from Marine Sponges Containing Dibrominated Indolic Systems

by Adriano Mollica, Marcello Locatelli, Azzurra Stefanucci and Francesco Pinnen

Molecules 2012, 17(5), 6083-6099; https://doi.org/10.3390/molecules17056083 - 21 May 2012

Cited by 68 | Viewed by 8443

Abstract

Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against different [...] Read more.

Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against different human diseases with possible applications in medicinal chemistry and in pharmaceutical fields, especially related to the new drug development process. Researchers have focused their attention principally on secondary metabolites with anti-cancer and cytotoxic activities. A common target for these molecules is the cytoskeleton, which has a central role in cellular proliferation, motility, and profusion involved in the metastatic process associate with tumors. In particular, many substances containing brominated indolic rings such as 5,6-dibromotryptamine, 5,6-dibromo-N-methyltryptamine, 5,6-dibromo-N-methyltryptophan (dibromoabrine), 5,6-dibromo-N,N-dimethyltryptamine and 5,6-dibromo-L-hypaphorine isolated from different marine sources, have shown anti-cancer activity, as well as antibiotic and anti-inflammatory properties. Considering the structural correlation between endogenous monoamine serotonin with marine indolic alkaloids 5,6-dibromoabrine and 5,6-dibromotryptamine, a potential use of some dibrominated indolic metabolites in the treatment of depression-related pathologies has also been hypothesized. Due to the potential applications in the treatment of various diseases and the increasing demand of these compounds for biological assays and the difficult of their isolation from marine sources, we report in this review a series of recent syntheses of marine dibrominated indole-containing products. Full article

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Open AccessArticle

Effects of Citrus aurantium (Bitter Orange) Fruit Extracts and p-Synephrine on Metabolic Fluxes in the Rat Liver

by Jéssica Sereno Peixoto, Jurandir Fernando Comar, Caroline Tessaro Moreira, Andréia Assunção Soares, Andrea Luiza De Oliveira, Adelar Bracht and Rosane Marina Peralta

Molecules 2012, 17(5), 5854-5869; https://doi.org/10.3390/molecules17055854 - 16 May 2012

Cited by 39 | Viewed by 13084

Abstract

The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic changes [...] Read more.

The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of the C. aurantium extract on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways, including oxygen uptake and perfusion pressure. The C. aurantium extract and p-synephrine increased glycogenolysis, glycolysis, oxygen uptake and perfusion pressure. These changes were partly sensitive to a- and b-adrenergic antagonists. p-Synephrine (200 mM) produced an increase in glucose output that was only 15% smaller than the increment caused by the extract containing 196 mM p-synephrine. At low concentrations the C. aurantium extract tended to increase gluconeogenesis, but at high concentrations it was inhibitory, opposite to what happened with p-synephrine. The action of the C. aurantium extract on liver metabolism is similar to the well known actions of adrenergic agents and can be partly attributed to its content in p-synephrine. Many of these actions are catabolic and compatible with the weight-loss effects usually attributed to C. aurantium. Full article

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Open AccessArticle

Mutagenicity of Flavonoids Assayed by Bacterial Reverse Mutation (Ames) Test

by Flavia Aparecida Resende, Wagner Vilegas, Lourdes Campaner Dos Santos and Eliana Aparecida Varanda

Molecules 2012, 17(5), 5255-5268; https://doi.org/10.3390/molecules17055255 - 7 May 2012

Cited by 116 | Viewed by 11404

Abstract

The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. [...] Read more.

The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. In the Ames assay, quercetin acted directly and its mutagenicity increased with metabolic activation. In the presence of S9 mix, kaempferol and galangin were mutagenic in the TA98 strain and kaempferol showed signs of mutagenicity in the other strains. The absence of hydroxyl groups, as in flavone, only signs of mutagenicity were shown in strain TA102, after metabolization and, among monohydroxylated flavones (3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone), the presence of hydroxyl groups only resulted in minor changes. Luteolin and fisetin also showed signs of mutagenicity in strain TA102. Finally, chrysin, which has only two hydroxy groups, at the 5-OH and 7-OH positions, also did not induce mutagenic activity in any of the bacterial strains used, under either activation condition. All the flavonoids were tested at concentrations varying from 2.6 to 30.7 nmol/plate for galangin and 12.1 to 225.0 nmol/plate for other flavonoids. In light of the above, it is necessary to clarify the conditions and the mechanisms that mediate the biological effects of flavonoids before treating them as therapeutical agents, since some compounds can be biotransformed into more genotoxic products; as is the case for galangin, kaempferol and quercetin. Full article

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571 KiB

Open AccessArticle

Synthesis of 2RS,4RS-1-[2-Phenyl-4-[2-(2-trifluromethoxy-phenoxy)-ethyl]-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-triazole Derivatives as Potent Inhibitors of Brassinosteroid Biosynthesis

by Kazuhiro Yamada, Yuko Yoshizawa and Keimei Oh

Molecules 2012, 17(4), 4460-4473; https://doi.org/10.3390/molecules17044460 - 13 Apr 2012

Cited by 22 | Viewed by 8695

Abstract

Brassinosteroids are important phytohormones that affect many aspects of plant growth and development. In order to manipulate brassinosteroid levels in plant tissues by using specific biosynthesis inhibitors, we have carried out a systemic search for specific inhibitors of brassinosteroid biosynthesis. Synthesis of triazole [...] Read more.

Brassinosteroids are important phytohormones that affect many aspects of plant growth and development. In order to manipulate brassinosteroid levels in plant tissues by using specific biosynthesis inhibitors, we have carried out a systemic search for specific inhibitors of brassinosteroid biosynthesis. Synthesis of triazole derivatives based on the ketoconazole scaffold revealed a series of novel brassinosteroid biosynthesis inhibitors (the YCZ series). To explore the structure-activity relationships of this synthetic series, we now report the synthesis of new triazole derivatives with different aromatic structures at position 2 of 1,3-dioxolane skeleton. We found that the variation of aromatic substituent significantly affect the inhibitory potency. Structure-activity relationships studies indicated that 4-chlorophenyl analogue is the most potent inhibitor of BR biosynthesis with an IC₅₀ value approximately 0.12 ± 0.04 µM, while a bulky biphenyl group exhibited a great negative effect on promoting the inhibitory potency with an IC₅₀ larger than 10 µM. Full article

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187 KiB

Open AccessArticle

Aminodi(hetero)arylamines in the Thieno[3,2-b]pyridine Series: Synthesis, Effects in Human Tumor Cells Growth, Cell Cycle Analysis, Apoptosis and Evaluation of Toxicity Using Non-Tumor Cells

by Ricardo C. Calhelha, Isabel C. F. R. Ferreira, Daniela Peixoto, Rui M. V. Abreu, Luís A. Vale-Silva, Eugénia Pinto, Raquel T. Lima, M. Inês Alvelos, M. Helena Vasconcelos and Maria-João R. P. Queiroz

Molecules 2012, 17(4), 3834-3843; https://doi.org/10.3390/molecules17043834 - 28 Mar 2012

Cited by 17 | Viewed by 8086

Abstract

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth [...] Read more.

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG₂ (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH₂ group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI₅₀ values (1.30–1.63 µM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels. Full article

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694 KiB

Open AccessArticle

IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

by Jikai Liu, Zhongbing Zhang, Yanni Xu, Tingting Feng, Wei Jiang, Zhuorong Li, Bin Hong, Zijian Xie and Shuyi Si

Molecules 2012, 17(3), 2833-2854; https://doi.org/10.3390/molecules17032833 - 7 Mar 2012

Cited by 4 | Viewed by 6033

Abstract

It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and [...] Read more.

It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS) method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO) cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein) expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791) was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [³H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell) further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC₅₀ of 25.23 μM. Full article

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538 KiB

Open AccessArticle

Identification of Dehydroxytrichostatin A as a Novel Up-Regulator of the ATP-Binding Cassette Transporter A1 (ABCA1)

by Yang Xu, Yanni Xu, Yi Bao, Bin Hong and Shuyi Si

Molecules 2011, 16(9), 7183-7198; https://doi.org/10.3390/molecules16097183 - 25 Aug 2011

Cited by 18 | Viewed by 7103

Abstract

The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I). ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. By using a cell-based screening model for the ABCA1 [...] Read more.

The ATP-binding cassette transporter A1 (ABCA1) mediates the cellular efflux of excess cholesterol and phospholipids to lipid-poor apolipoprotein A-I (apoA-I). ABCA1 plays an important role in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. By using a cell-based screening model for the ABCA1 up-regulator and column chromatography, an active compound, 9179B, was isolated. Through analysis of its NMR data, 9179B was identified as dehydroxytrichostatin A. We found that 9179B increased the transcription of ABCA1 in a cell-based reporter assay, with an EC₅₀ value of 2.65 μM. 9179B up-regulated ABCA1 expression at both mRNA and protein levels in HepG2 and RAW264.7 cells. It also up-regulated the expression of scavenger receptor class B type I (SR-BI) as well as the uptake of DiI-HDL in RAW264.7 cells. This compound stimulated ApoA-I-mediated cellular cholesterol efflux from RAW 264.7 cells. We further found that 9179B was a potent histone deacetylase (HDAC) inhibitor with an IC₅₀ value of 0.08 μM. Reporter gene assays showed that the regulation of ABCA1 transcription by 9179B was mainly mediated by the −171/−75 bp promoter region. Together, our results indicate that 9179B is an ABCA1 up-regulator and dehydroxytrichostatin A may be a novel anti-atherogenic compound. Full article

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369 KiB

Open AccessArticle

Chemical Profile and Biological Potential of Non-Polar Fractions from Centroceras clavulatum (C. Agardh) Montagne (Ceramiales, Rhodophyta)

by Otávio P. Rocha, Rafael De Felício, Ana Helena B. Rodrigues, Daniela L. Ambrósio, Regina Maria B. Cicarelli, Sérgio De Albuquerque, Maria Claudia M. Young, Nair S. Yokoya and Hosana M. Debonsi

Molecules 2011, 16(8), 7105-7114; https://doi.org/10.3390/molecules16087105 - 19 Aug 2011

Cited by 17 | Viewed by 8653

Abstract

The present study reports the Gas Chromatography-Mass Spectrometry (GC-MS) evaluation of the hexanes and dichloromethane fractions from extracts of the red alga Centroceras clavulatum (C. Agardh) Montagne. Twenty three compounds were identified, totaling ca. 42% of both fractions (0.18 g mass extract). The [...] Read more.

The present study reports the Gas Chromatography-Mass Spectrometry (GC-MS) evaluation of the hexanes and dichloromethane fractions from extracts of the red alga Centroceras clavulatum (C. Agardh) Montagne. Twenty three compounds were identified, totaling ca. 42% of both fractions (0.18 g mass extract). The main constituents of the fractions were hexadecanoic acid (17.6%) and pentadecanoic acid (15.9%). Several secondary metabolites with interesting biological activity, such as (-)-loliolide, neophytadiene, phytol were identified. In addition, several classes of secondary metabolites, including phenolic compounds (e.g., phenylacetic acid), terpene derivatives, fatty acids, halogenated compound (e.g., 2-chlorocyclohexenol), lignoids, steroids, esters, amides (e.g., hexadecanamide), ketones, carboxylic acids, aldehydes and alcohols were observed. The occurrence of several of these structural classes is described for the first time in this species. The same fractions analyzed by GC-MS, and a separate set of polar fractions, were evaluated against two life cycle stages (epimastigote and trypomastigote forms) of the protozoan Trypanosoma cruzi and against phytopatogenic fungi Cladosporium cladosporiodes and C. sphaerospermum. The dichloromethane fraction was active against both T. cruzi forms (epimastigote IC₅₀ = 19.1 μg.mL⁻¹ and trypomastigote IC₅₀ = 76.2 μg.mL⁻¹). The hexanes and ethyl acetate fractions also displayed activity against both fungi species (200 μg) by TLC-bioautography. Full article

147 KiB

Open AccessArticle

Absorbable Phenylpropenoyl Sucroses from Polygala tenuifolia

by Gaimei She, Yinying Ba, Yang Liu, Hang Lv, Wei Wang and Renbing Shi

Molecules 2011, 16(7), 5507-5513; https://doi.org/10.3390/molecules16075507 - 29 Jun 2011

Cited by 14 | Viewed by 6967

Abstract

Three phenylpropenoyl sucroses – sibiricose A5 (1), A6 (2) and 3′,6-disinapoyl sucrose (3) – were isolated from the 30% EtOH extract of Polygala tenuifolia, which displayed antidepressant-like action. HPLC analysis indicated that the three phenylpropenoyl sucroses [...] Read more.

Three phenylpropenoyl sucroses – sibiricose A5 (1), A6 (2) and 3′,6-disinapoyl sucrose (3) – were isolated from the 30% EtOH extract of Polygala tenuifolia, which displayed antidepressant-like action. HPLC analysis indicated that the three phenylpropenoyl sucroses could be absorbed into serum. From the serum pharmacochemistry point of view, these three phenylpropenoyl sucroses might prevent or relieve depression. Full article

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341 KiB

Open AccessReview

The Main Anticancer Bullets of the Chinese Medicinal Herb, Thunder God Vine

by Zi Liu, Liang Ma and Guang-Biao Zhou

Molecules 2011, 16(6), 5283-5297; https://doi.org/10.3390/molecules16065283 - 23 Jun 2011

Cited by 113 | Viewed by 16121

Abstract

The thunder god vine or Tripterygium wilfordii Hook. F. is a representative Chinese medicinal herb which has been used widely and successfully for centuries in treating inflammatory diseases. More than 100 components have been isolated from this plant, and most of them have [...] Read more.

The thunder god vine or Tripterygium wilfordii Hook. F. is a representative Chinese medicinal herb which has been used widely and successfully for centuries in treating inflammatory diseases. More than 100 components have been isolated from this plant, and most of them have potent therapeutic efficacy for a variety of autoimmune and inflammatory diseases. In the past four decades, the anticancer activities of the extracts from this medicinal herb have attracted intensive attention by researchers worldwide. The diterpenoid epoxide triptolide and the quinone triterpene celastrol are two important bioactive ingredients that show a divergent therapeutic profile and can perturb multiple signal pathways. Both compounds promise to turn traditional medicines into modern drugs. In this review, we will mainly address the anticancer activities and mechanisms of action of these two agents and briefly describe some other antitumor components of the thunder god vine. Full article

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211 KiB

Open AccessArticle

Biomolecule Profiles in Inedible Wild Mushrooms with Antioxidant Value

by Filipa S. Reis, Eliana Pereira, Lillian Barros, Maria João Sousa, Anabela Martins and Isabel C.F.R. Ferreira

Molecules 2011, 16(6), 4328-4338; https://doi.org/10.3390/molecules16064328 - 25 May 2011

Cited by 68 | Viewed by 13369

Abstract

The use of natural products isolated from mushrooms, included inedible species, against infection, cancer diseases and other oxidative-stress related diseases is one of the cornerstones of modern medicine. In the present work, the antioxidant molecule profiles of inedible mushroom species were evaluated and [...] Read more.

The use of natural products isolated from mushrooms, included inedible species, against infection, cancer diseases and other oxidative-stress related diseases is one of the cornerstones of modern medicine. In the present work, the antioxidant molecule profiles of inedible mushroom species were evaluated and compared with those of edible species. The order of antioxidant abundance found in inedible wild mushrooms was: phenolics > flavonoids > ascorbic acid > tocopherols > carotenoids, similar to that of edible species. Furthermore the same energetic biomolecules were found including the disaccharide trehalose, the monosaccharide alcohol derivative mannitol and the fatty acids palmitic, oleic and linoleic acids. Fomitopsis pinicola revealed a very high phenolics concentration (388 mg GAE/g extract) and powerful antioxidant properties, mainly reducing power (EC₅₀ value 60 μg/mL similar to the standard Trolox^®). It could find applications in the prevention of free radical-related diseases as a source of bioactive compounds. Full article

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181 KiB

Open AccessArticle

Chemical Composition, and Antioxidant and Antimicrobial Activities of Essential Oil of Phyllostachys heterocycla cv. Pubescens Varieties from China

by Yong-Chun Jin, Ke Yuan and Jing Zhang

Molecules 2011, 16(5), 4318-4327; https://doi.org/10.3390/molecules16054318 - 24 May 2011

Cited by 23 | Viewed by 7607

Abstract

The essential oils of Phyllostachys heterocycla cv. Pubescens, Phyllostachys heterocycla cv. Gracilis, Phyllostachys heterocycla cv. Heterocycla and Phyllostachys kwangsiensis leaves were obtained by steam distillation. Their chemical components were separated and identified by gas chromatography/mass spectrometry (GC/MS). Meanwhile, the effect of [...] Read more.

The essential oils of Phyllostachys heterocycla cv. Pubescens, Phyllostachys heterocycla cv. Gracilis, Phyllostachys heterocycla cv. Heterocycla and Phyllostachys kwangsiensis leaves were obtained by steam distillation. Their chemical components were separated and identified by gas chromatography/mass spectrometry (GC/MS). Meanwhile, the effect of scavenging free radicals of essential oil was assayed by using the DPPH·method with Trolox^® as control to evaluate their antioxidant capacities. Gram-positive (Staphyloccocus aureus) and Gram-negative (Escherichia coli) were selected as the indicator microorganisms to evaluate the antimicrobial activity. Antimicrobial properties were estimated by the agar diffusion method. The results show that 63 components were separated and identified by GC/MS from these varieties of bamboo leaves. cis-3-Hexenol, whose content in cv. Pubescens, Gracilis, Heterocycla and Ph. kwangsiensis was 27.11%, 24.62%, 30.51% and 34.65%, respectively, was the main constituent. The relative content of alcohol compounds in these varieties of essential oils ranged from 39.8% to 46.64%. All of the bamboo leaf essential oils possessed certain antioxidant capacity; the corresponding IC₅₀ values were 3.1622, 4.9353, 4.2473, and 5.4746 μL/mL, respectively. Essential oils of all tested bamboo spp. were active against Staphylococcus epidermidis and E. coli, showing a positive correlation with the essential oil concentration of 50.42-300 μL/mL. The results indicated there were no significant differences among three varieties and the related species with respect to their antioxidant and antimicrobial activities. This paper provides evidence for studying the essential composition from different varieties of bamboo leaves. Full article

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506 KiB

Open AccessArticle

A Screening of a Library of T7 Phage-Displayed Peptide Identifies E2F-4 as an Etoposide-Binding Protein

by Mihoko Takami, Yoichi Takakusagi, Kouji Kuramochi, Senko Tsukuda, Satoko Aoki, Kengo Morohashi, Keisuke Ohta, Susumu Kobayashi, Kengo Sakaguchi and Fumio Sugawara

Molecules 2011, 16(5), 4278-4294; https://doi.org/10.3390/molecules16054278 - 24 May 2011

Cited by 12 | Viewed by 7600

Abstract

Etoposide (VP-16) is an anti-tumor compound that targets topoisomerase II (top II). In this study, we have identified an alternative binding protein of etoposide by screening a library of T7 phage-displayed peptides. After four rounds of selection using a biotinylated etoposide derivative immobilized [...] Read more.

Etoposide (VP-16) is an anti-tumor compound that targets topoisomerase II (top II). In this study, we have identified an alternative binding protein of etoposide by screening a library of T7 phage-displayed peptides. After four rounds of selection using a biotinylated etoposide derivative immobilized on a streptavidin-coated plate, T7 phage particles that display a 16-mer peptide NSSASSRGNSSSNSVY (ETBP16) or a 10-mer NSLRKYSKLK (ETBP10) were enriched with the ratio of 40 or 11 out of the 69 clones, respectively. Binding of etoposide to these peptides was confirmed by surface plasmon resonance (SPR) analysis, which showed ETBP16 and ETBP10 to have a kinetic constant of 4.85 × 10⁻⁵ M or 6.45 × 10⁻⁵ M, respectively. ETBP16 displays similarity with the ser-rich domain in E2F-4, a transcription factor in cell cycle-regulated genes, suggesting that etoposide might interact with E2F-4 via this domain. SPR analysis confirmed the specific binding of etoposide to recombinant E2F-4 is in the order of 10⁻⁵ M. Furthermore, etoposide was shown to inhibit luciferase reporter gene expression mediated by the heterodimeric E2F-4/DP complex. Taken together, our results suggest that etoposide directly binds to E2F-4 and inhibits subsequent gene transcription mediated by heterodimeric E2F-4/DP complexes in the nucleus. Full article

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399 KiB

Open AccessArticle

Cytotoxicity and Pro-Apoptotic Activity of 2,2´-Bis[4,5-bis(4-hydroxybenzyl)-2-(4-hydroxyphenyl)cyclopent-4-en-1,3-dione], a Phenolic Cyclopentenedione Isolated from the Cyanobacterium Strain Nostoc sp. str. Lukešová 27/97

by Jan Vacek, Jan Hrbáč, Jiří Kopecký and Jitka Vostálová

Molecules 2011, 16(5), 4254-4263; https://doi.org/10.3390/molecules16054254 - 23 May 2011

Cited by 9 | Viewed by 6663

Abstract

The cytotoxicity of the polyphenol 2,2´-bis[4,5-bis(4-hydroxybenzyl)-2-(4-hydroxyphenyl)cyclopent-4-en-1,3-dione], nostotrebin 6 (NOS-6), was tested under in vitro conditions using mouse fibroblasts (BALB/c cells). Identification of NOS-6 and its uptake into fibroblasts was examined by multi-stage mass spectrometry analysis with the following fragmentation pattern: MS (m/z [...] Read more.

The cytotoxicity of the polyphenol 2,2´-bis[4,5-bis(4-hydroxybenzyl)-2-(4-hydroxyphenyl)cyclopent-4-en-1,3-dione], nostotrebin 6 (NOS-6), was tested under in vitro conditions using mouse fibroblasts (BALB/c cells). Identification of NOS-6 and its uptake into fibroblasts was examined by multi-stage mass spectrometry analysis with the following fragmentation pattern: MS (m/z) [M+H]⁺ 799.1 → MS² 399.1 → MS³ 305.1 → MS⁴ 277.1. Using several cell viability assays, the IC₅₀ of NOS-6 after 24 h incubation was found to be 8.48 ± 0.16/12.15 ± 1.96 µM (neutral red/MTT assay) which was higher than that of doxorubicin. It was found that NOS-6 is capable of inducing both types of cell death, apoptosis and necrosis in a dose-dependent manner. The biological activities of the cyclopentenediones and preliminary data on NOS-6 cytotoxicity are discussed. Full article

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887 KiB

Open AccessArticle

Consecutive Low Doses of Cyclosporine A Induce Pro-Inflammatory Cytokines and Accelerate Allograft Skin Rejection

by Roberto López-Flores, Rafael Bojalil, José C. Benítez, Yadira Ledesma-Soto, César A. Terrazas, Miriam Rodríguez-Sosa and Luis I. Terrazas

Molecules 2011, 16(5), 3969-3984; https://doi.org/10.3390/molecules16053969 - 11 May 2011

Cited by 12 | Viewed by 8934

Abstract

Cyclosporine A (CsA) is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of [...] Read more.

Cyclosporine A (CsA) is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of CsA used. To test the hypothesis that minimal doses of CsA may show different outcomes on grafts, we used an experimental model for skin transplants in mice. ICR outbred mice received skin allografts and were either treated daily with different doses of CsA or left untreated. Untreated mice showed allograft rejection within 14 days, with graft necrosis, infiltration of neutrophils and macrophages and displayed high percentages of CD8⁺ T cells in the spleens, which were associated with high serum levels of IL-12, IFN-g and TNF-α. As expected, mice treated with therapeutic doses of CsA (15 mg/kg) did not show allograft rejection within the follow-up period of 30 days and displayed the lowest levels of IL-12, IFN-g and TNF-α as well as a reduction in CD8⁺ lymphocytes. In contrast, mice treated with consecutive minimal doses of CsA (5 × 10⁻⁵⁵ mg/kg) displayed an acute graft rejection as early as one to five days after skin allograft; they also displayed necrosis and strong inflammatory infiltration that was associated with high levels of IL-12, IFN-g and TNF-α. Moreover, the CD4⁺ CD25^hiFoxP3⁺ subpopulation of cells in the spleens of these mice was significantly inhibited compared with animals that received the therapeutic treatment of CsA and those treated with placebo. Our data suggest that consecutive, minimal doses of CsA may affect Treg cells and may stimulate innate immunity. Full article

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229 KiB

Open AccessArticle

Inhibition of Inflammatory Mediators by Neobavaisoflavone in Activated RAW264.7 Macrophages

by Ewelina Szliszka, Dariusz Skaba, Zenon P. Czuba and Wojciech Krol

Molecules 2011, 16(5), 3701-3712; https://doi.org/10.3390/molecules16053701 - 3 May 2011

Cited by 81 | Viewed by 9642

Abstract

Flavonoids and coumarins are the major bioactive constituents identified in Psoralea corylifolia. The active fraction isolated from fruits, seeds and roots possesses antibacterial, antioxidative and immunomodulatory properties. Neobavaisoflavone is one of the flavonoids found in Psoralea corylifolia. In the present study we [...] Read more.

Flavonoids and coumarins are the major bioactive constituents identified in Psoralea corylifolia. The active fraction isolated from fruits, seeds and roots possesses antibacterial, antioxidative and immunomodulatory properties. Neobavaisoflavone is one of the flavonoids found in Psoralea corylifolia. In the present study we investigated in vitro the anti-inflammatory activity of neobavaisoflavone. Macrophages play an important role in inflammation through the release of inflammatory mediators involved in the immune response. Inappropriate and prolonged macrophage activation is largely responsible for the pathology of acute and chronic inflammatory conditions. Neobavaisoflavone significantly inhibited the production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokines: IL-1β, IL-6, IL-12p40, IL-12p70, TNF-α in LPS+IFN-γ– or PMA– stimulated RAW264.7 macrophages. Full article

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299 KiB

Open AccessArticle

Gombapyrones E and F, New α-Pyrone Polyenes Produced by Streptomyces sp. KMC-002

by Hyun Bong Park, Hyun Ok Yang, Kang Ro Lee and Hak Cheol Kwon

Molecules 2011, 16(5), 3519-3529; https://doi.org/10.3390/molecules16053519 - 26 Apr 2011

Cited by 10 | Viewed by 8275

Abstract

Microorganism-derived polyene polyketides have been shown to display a variety of biological activities and have attracted great interest due to their structurally intriguing chemical diversity. Two new polyenes were isolated from a culture broth of Streptomyces sp. KMC-002 obtained from a soil sample [...] Read more.

Microorganism-derived polyene polyketides have been shown to display a variety of biological activities and have attracted great interest due to their structurally intriguing chemical diversity. Two new polyenes were isolated from a culture broth of Streptomyces sp. KMC-002 obtained from a soil sample in an abandoned mine. The structures of these compounds were determined to be α-pyrone-containing polyene analogues through analyses of HRFABMS, UV and NMR data, and were named Gombapyrones E (1) and F (2). Gombapyrone E (1) showed antibacterial activity against Micrococcus luteus, Enterococcus hirae, Staphylococcus aureus and MRSA. Full article

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246 KiB

Open AccessArticle

Study of the Biological Activity of Novel Synthetic Compounds with Antiviral Properties against Human Rhinoviruses

by Samuela Laconi, Maria A. Madeddu and Raffaello Pompei

Molecules 2011, 16(5), 3479-3487; https://doi.org/10.3390/molecules16053479 - 26 Apr 2011

Cited by 6 | Viewed by 8170

Abstract

Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the [...] Read more.

Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir’s main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI) on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602) resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir’s central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses. Full article

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132 KiB

Open AccessCommunication

Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease

by Jean Leandro Dos Santos, Priscila Longhin Bosquesi, Eliana Aparecida Varanda, Lídia Moreira Lima and Man Chin Chung

Molecules 2011, 16(4), 2982-2989; https://doi.org/10.3390/molecules16042982 - 6 Apr 2011

Cited by 3 | Viewed by 8231

Abstract

The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (C6 [...] Read more.

The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1–C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms. Full article

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250 KiB

Open AccessArticle

Synthesis and Herbicidal Activity of 5-(4-Hydroxybenzyl)-2-Thioxoimidazolidin-4-one Esters

by Jintao Han, Jinmin Wang, Hongbo Dong, Jianping Lei, Mingan Wang and Jianxin Fang

Molecules 2011, 16(4), 2833-2845; https://doi.org/10.3390/molecules16042833 - 30 Mar 2011

Cited by 19 | Viewed by 7842

Abstract

A series of novel 5-(4-hydroxybenzyl)-2-thioxoimidazolidin-4-one esters were synthesized under mild conditions by the reaction of 5-(4-hydroxybenzyl)-2-thioxoimidazolidin-4-one and carboxylic acids with DCC and DMAP as the promoters. Their structures were confirmed by ¹H-NMR, IR, ESI-MS and elemental analysis. The preliminary bioassy results indicated [...] Read more.

A series of novel 5-(4-hydroxybenzyl)-2-thioxoimidazolidin-4-one esters were synthesized under mild conditions by the reaction of 5-(4-hydroxybenzyl)-2-thioxoimidazolidin-4-one and carboxylic acids with DCC and DMAP as the promoters. Their structures were confirmed by ¹H-NMR, IR, ESI-MS and elemental analysis. The preliminary bioassy results indicated that some of compounds exhibit good herbicidal activity against Zea mays, Triticum aestivum and Arabidopsis thaliana. The further greenhouse test showed that compounds 6-16 and 6-28 have 60%, 50% and 50% efficacy against Stellaria media, Echinochloa crus-galli and Setaria viridis at 1,000 g/ha, respectively. Full article

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222 KiB

Open AccessReview

Effects of Panax ginseng on Tumor Necrosis Factor-α-Mediated Inflammation: A Mini-Review

by Davy CW Lee and Allan SY Lau

Molecules 2011, 16(4), 2802-2816; https://doi.org/10.3390/molecules16042802 - 30 Mar 2011

Cited by 100 | Viewed by 11715

Abstract

Panax ginseng is one of the most commonly used Chinese medicines in China, Asia and Western countries. The beneficial effects of ginseng have been attributed to the biological activities of its constituents, the ginsenosides. In this review, we summarize recent publications on the [...] Read more.

Panax ginseng is one of the most commonly used Chinese medicines in China, Asia and Western countries. The beneficial effects of ginseng have been attributed to the biological activities of its constituents, the ginsenosides. In this review, we summarize recent publications on the anti-inflammatory effects of ginseng extracts and ginsenosides on cellular responses triggered by different inducers including endotoxin, tumor necrosis factor-alpha (TNF-α), interferon-gamma and other stimuli. Proinflammatory cytokines, chemokines, adhesion molecules and mediators of inflammation including inducible nitric oxide synthase, cyclooxygenase-2 and nitric oxide orchestrate the inflammatory response. Ginseng extracts and ginsenosides including Rb₁, Rd, Rg₁, Rg₃, Rh₁, Rh₂, Rh₃and Rp₁ have been reported to have anti-inflammatory properties in different studies related to inflammation. Ginsenosides inhibit different inducers-activated signaling protein kinases and transcription factor nuclear factor-kappaB leading to decreases in the production of cytokines and mediators of inflammation. The therapeutic potential of ginseng on TNF-α-mediated inflammatory diseases is also discussed. Taken together, this summary provides evidences for the anti-inflammatory effects of ginseng extracts and ginsenosides as well as the underlying mechanisms of their effects on inflammatory diseases. Full article

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Open AccessArticle

Cytotoxic Metabolites from the Soil-Derived Fungus Exophiala Pisciphila

by Cui-Cui Wang, Hai-Zhou Liu, Ming Liu, Yu-Yan Zhang, Tian-Tian Li and Xiu-Kun Lin

Molecules 2011, 16(4), 2796-2801; https://doi.org/10.3390/molecules16042796 - 30 Mar 2011

Cited by 7 | Viewed by 7892

Abstract

A new polyketide compound 1 and a new naturally occurring chromone derivative 2, along with two known indole alkaloids 3–4 were characterized from the ethyl acetate extract of a soil-derived fungal strain, Exophiala pisciphila PHF-9. The structures of compounds 1 [...] Read more.

A new polyketide compound 1 and a new naturally occurring chromone derivative 2, along with two known indole alkaloids 3–4 were characterized from the ethyl acetate extract of a soil-derived fungal strain, Exophiala pisciphila PHF-9. The structures of compounds 1–4 were established by detailed spectroscopic analysis and comparison with literature data. The absolute configuration of 1 was determined by a modified Mosher’s method. Compound 1 exhibited moderate cytotoxicity against A-549, Hela, PANC-28 and BEL-7402 cell lines. Full article

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301 KiB

Open AccessArticle

Antifeedant Triterpenoids from the Seeds and Bark of Lansium domesticum cv Kokossan (Meliaceae)

by Tri Mayanti, Roekmiati Tjokronegoro, Unang Supratman, Mat Ropi Mukhtar, Khalijah Awang and A. Hamid A. Hadi

Molecules 2011, 16(4), 2785-2795; https://doi.org/10.3390/molecules16042785 - 29 Mar 2011

Cited by 42 | Viewed by 7717

Abstract

Two tetranortriterpenoids, kokosanolide A (1) and C (2) were isolated from the seeds and three onoceranoid-type triterpenoids: kokosanolide B (3), 8,14-secogammacera-7,14-diene-3,21-dione (4) and a 1.5:0.5 mixture of 8,14-secogammacera-7,14(27)-diene-3,21-dione (5) and compound 4 were isolated [...] Read more.

Two tetranortriterpenoids, kokosanolide A (1) and C (2) were isolated from the seeds and three onoceranoid-type triterpenoids: kokosanolide B (3), 8,14-secogammacera-7,14-diene-3,21-dione (4) and a 1.5:0.5 mixture of 8,14-secogammacera-7,14(27)-diene-3,21-dione (5) and compound 4 were isolated from the bark of kokossan (Lansium domesticum). Complete ¹H- and ¹³C-NMR data of the triterpenoids 1-5 are reported. The triterpenoids’ structures were elucidated primarily by means of high field 1D- and 2D-NMR, IR and HRMS spectral data. Triterpenoids 1-5 exhibited moderate to strong antifeedant activity against the fourth instar larvae of Epilachna vigintioctopunctata. Full article

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Open AccessArticle

Lignans and Other Constituents from Aerial Parts of Haplophyllum Villosum

by Parimah Parhoodeh, Mawardi Rahmani, Najihah Mohd Hashim, Mohd Aspollah Sukari and Gwendoline Ee Cheng Lian

Molecules 2011, 16(3), 2268-2273; https://doi.org/10.3390/molecules16032268 - 7 Mar 2011

Cited by 17 | Viewed by 6310

Abstract

During our phytochemical investigation of Haplophyllum villosum (Rutaceae), a perennial herb from Iran, a new 4,8-diaryl-3,7-dioxobicyclo-(3,3,0)-octane type lignan, eudesmin A (1), together with four known compounds–eudesmin (2), haplamine (3), umbelliferone (4) and scopoletin (5 [...] Read more.

During our phytochemical investigation of Haplophyllum villosum (Rutaceae), a perennial herb from Iran, a new 4,8-diaryl-3,7-dioxobicyclo-(3,3,0)-octane type lignan, eudesmin A (1), together with four known compounds–eudesmin (2), haplamine (3), umbelliferone (4) and scopoletin (5)–were isolated from aerial parts of the plant. The structures of the compounds were elucidated using NMR spectral analysis (¹H-NMR,¹³C-NMR, HSQC, COSY and HMBC) as well as UV, IR and MS spectra and comparison with previously reported data. Full article

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214 KiB

Open AccessArticle

Diterpenoid Tanshinones and Phenolic Acids from Cultured Hairy Roots of Salvia miltiorrhiza Bunge and Their Antimicrobial Activities

by Jianglin Zhao, Jingfeng Lou, Yan Mou, Peiqin Li, Jianyong Wu and Ligang Zhou

Molecules 2011, 16(3), 2259-2267; https://doi.org/10.3390/molecules16032259 - 7 Mar 2011

Cited by 77 | Viewed by 10606

Abstract

Four diterpenoid tanshinones and three phenolic acids were isolated from the crude ethanol extract of the cultured hairy roots of Salvia miltiorrhiza Bunge by bioassay-guided fractionation. By means of physicochemical and spectrometric analysis, they were identified as tanshinone ΙΙA (1), tanshinone [...] Read more.

Four diterpenoid tanshinones and three phenolic acids were isolated from the crude ethanol extract of the cultured hairy roots of Salvia miltiorrhiza Bunge by bioassay-guided fractionation. By means of physicochemical and spectrometric analysis, they were identified as tanshinone ΙΙA (1), tanshinone Ι (2), cryptotanshinone (3), dihydrotanshinone Ι (4), rosmarinic acid (5), caffeic acid (6), and danshensu (7). These compounds were evaluated to show a broad antimicrobial spectrum of activity on test microorganisms including eight bacterial and one fungal species. Among the four tanshinones, cryptotanshinone (3) and dihydrotanshinone Ι (4) exhibited stronger antimicrobial activity than tanshinone ΙΙA (1) and tanshinone Ι (2). The results indicated that the major portion of the antimicrobial activity was due to the presence of tanshinones and phenolic acids in S. miltiorrhiza hairy roots, which could be used as the materials for producing antimicrobial agents for use in agricultural practice in the future. Full article

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Open AccessArticle

Dihydroberkleasmin A: A New Eremophilane Sesquiterpenoid from the Fermentation Broth of the Plant Endophytic Fungus Pestalotiopsis photiniae

by Xiao-Long Yang, Su Zhang, Hua-Jie Zhu and Du-Qiang Luo

Molecules 2011, 16(2), 1910-1916; https://doi.org/10.3390/molecules16021910 - 23 Feb 2011

Cited by 18 | Viewed by 6980

Abstract

Dihydroberkleasmin A (1), a new ester-substituted sesquiterpenoid related to the eremophilane class, together with the known compound berkleasmin C (2), were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis photiniae. The structure of dihydroberkleasmin A [...] Read more.

Dihydroberkleasmin A (1), a new ester-substituted sesquiterpenoid related to the eremophilane class, together with the known compound berkleasmin C (2), were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis photiniae. The structure of dihydroberkleasmin A (1) was elucidated by extensive spectroscopic analysis. The stereochemistry was assigned by comparison of the NMR spectroscopic data with those of berkleasmin A. Full article

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147 KiB

Open AccessArticle

Eucalyptus oleosa Essential Oils: Chemical Composition and Antimicrobial and Antioxidant Activities of the Oils from Different Plant Parts (Stems, Leaves, Flowers and Fruits)

by Hajer Naceur Ben Marzoug, Mehrez Romdhane, Ahmed Lebrihi, Florence Mathieu, François Couderc, Manef Abderraba, Mohamed Larbi Khouja and Jalloul Bouajila

Molecules 2011, 16(2), 1695-1709; https://doi.org/10.3390/molecules16021695 - 17 Feb 2011

Cited by 147 | Viewed by 17195

Abstract

Essential oils obtained by hydrodistillation from the different parts (stems, adult leaves, immature flowers and fruits) of Eucalyptus oleosa were screened for their antioxidant and antimicrobial properties and their chemical composition. According to GC-FID and GC-MS, the principal compound of the stem, immature [...] Read more.

Essential oils obtained by hydrodistillation from the different parts (stems, adult leaves, immature flowers and fruits) of Eucalyptus oleosa were screened for their antioxidant and antimicrobial properties and their chemical composition. According to GC-FID and GC-MS, the principal compound of the stem, immature flowers and the fruit oils was 1,8-cineole, representing 31.5%, 47.0% and 29.1%, respectively. Spathulenol (16.1%) and γ-eudesmol (15.0%) were the two principal compounds of adult leaves oil. In the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, the oils of the four parts showed moderate antioxidant activity. In the ABTS (2,2’-azinobis-3-ethylbenzothiazoline-6-sulphonate) assay, the most active part was the adult leaves, with a IC₅₀ value 13.0 ± 0.6 mg/L, followed by stems (IC₅₀ = 43.5 ± 1.4 mg/L). The essential oils showed a better antibacterial activity against Gram-positive and Gram-negative bacteria, and a significant antifungal activity also was observed against yeast-like fungi. A strong correlations between oxygenated monoterpenes and antimicrobial activity (especially 1,8-cineole) were noted (R² = 0.99, 0.97 and 0.79 for B. subtilis, P. aeruginosa and C. albicans, respectively). Full article

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225 KiB

Open AccessArticle

Fast and Sensitive LC-DAD-ESI/MS Method for Analysis of Saikosaponins c, a, and d from the Roots of Bupleurum Falcatum (Sandaochaihu)

by Li-Chun Zhao, Wei Li, Yu-Fang He, Xiao-Hua Li, Zi Wang, Wen-Cong Liu, Yi-Nan Zheng and Jian Liang

Molecules 2011, 16(2), 1533-1543; https://doi.org/10.3390/molecules16021533 - 11 Feb 2011

Cited by 6 | Viewed by 13559

Abstract

In the present study, we developed a liquid chromatography-diode array detector-electrospray ionization/mass spectrometric (LC-DAD-ESI/MS) method for analysis of saikosaponins in Bupleurum falcatum. The LC method employed a ZORBAX SB-Aq analytical column (150 × 4.6 mm i.d., 5 μm) at a flow rate [...] Read more.

In the present study, we developed a liquid chromatography-diode array detector-electrospray ionization/mass spectrometric (LC-DAD-ESI/MS) method for analysis of saikosaponins in Bupleurum falcatum. The LC method employed a ZORBAX SB-Aq analytical column (150 × 4.6 mm i.d., 5 μm) at a flow rate of 0.8 mL/min coupled with a diode array detector at 204 nm. A step gradient of acetonitrile-water (v/v) containing 0.5% formic acid from 30 to 70% was applied, leading to a sample analysis time of 30 min. The ESI-MS was carried out in positive and negative modes from 500 to 1,500 m/z. Saikosaponins c, a, and d gave strong sodium adducts at m/z 949.6, 803.5 and 803.6, respectively, in positive mode. The data indicate that the present LC-DAD-ESI/MS assay is an effective method for the determination of saikosaponins c, a and d from the roots of Bupleurum falcatum. Full article

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2010

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163 KiB

Open AccessArticle

Evaluation of the Bioactivity of Novel Spiroisoxazoline TypeCompounds against Normal and Cancer Cell Lines

by Nigar Najim, Yaser Bathich, Mazatulikhma Mat Zain, Ahmad Sazali Hamzah and Zurina Shaameri

Molecules 2010, 15(12), 9340-9353; https://doi.org/10.3390/molecules15129340 - 17 Dec 2010

Cited by 25 | Viewed by 7936

Abstract

The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). [...] Read more.

The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease. Full article

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222 KiB

Open AccessArticle

Antimicrobial Activity of Sphingolipids Isolated from the Stems of Cucumber (Cucumis sativus L.)

by Jing Tang, Xiangjie Meng, Hao Liu, Jianglin Zhao, Ligang Zhou, Minghua Qiu, Xianming Zhang, Zhu Yu and Fuyu Yang

Molecules 2010, 15(12), 9288-9297; https://doi.org/10.3390/molecules15129288 - 15 Dec 2010

Cited by 36 | Viewed by 11720

Abstract

Three antimicrobial sphingolipids were separated by bioassay-guided isolation from the chloroform fraction of the crude methanol extract of cucumber (Cucumis sativus L.) stems and identified as (2S,3S,4R,10E)-2-[(2'R)-2-hydroxytetra-cosanoylamino]-1,3,4-octadecanetriol-10-ene (1), 1-O-β-D-glucopyranosyl(2S,3S,4R,10E [...] Read more.

Three antimicrobial sphingolipids were separated by bioassay-guided isolation from the chloroform fraction of the crude methanol extract of cucumber (Cucumis sativus L.) stems and identified as (2S,3S,4R,10E)-2-[(2'R)-2-hydroxytetra-cosanoylamino]-1,3,4-octadecanetriol-10-ene (1), 1-O-β-D-glucopyranosyl(2S,3S,4R,10E)-2-[(2'R)-2-hydroxy-tetracosanoylamino]-1,3,4-octadecanetriol-10-ene (2) and soya-cerebroside I (3) by their physicochemical properties and spectroscopic analysis. They were evaluated to show antifungal and antibacterial activity on test microorganisms including four fungal and three bacterial species. Among them, compound 1, a relatively low polarity aglycone, exhibited stronger antimicrobial activity than its corresponding glycoside 2. The results indicated that sphingolipids could be the main antimicrobial compounds in the crude methanol extract of cucumber stems. Full article

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652 KiB

Open AccessArticle

Apoptotic Effects of γ-Mangostin from the Fruit Hull of Garcinia mangostana on Human Malignant Glioma Cells

by Hui-Fang Chang, Wen-Tsung Huang, Hui-Ju Chen and Ling-Ling Yang

Molecules 2010, 15(12), 8953-8966; https://doi.org/10.3390/molecules15128953 - 7 Dec 2010

Cited by 41 | Viewed by 12612

Abstract

Gliomas are a common type of primary brain tumor with glioblastoma multiforme accounting for the majority of human brain tumors. In this paper, high grade human malignant glioblastomas (MGs) including U87 MG and GBM 8401 were used to evaluate the antitumor effects of [...] Read more.

Gliomas are a common type of primary brain tumor with glioblastoma multiforme accounting for the majority of human brain tumors. In this paper, high grade human malignant glioblastomas (MGs) including U87 MG and GBM 8401 were used to evaluate the antitumor effects of γ-mangostin, a xanthone derivative isolated and purified from the hull of the tropical fruit Garcinia mangostana. The γ-mangostin showed potent antiproliferative activity toward MGs in dose- and time-dependent manners. In addition, flow cytometric analysis of cell morphology in the apoptotic cells revealed an increase in hypodiploid cells in γ-mangostin treated U87 MG and GBM 8401 cells, while significant enhancement of intracellular peroxide production was detected in the same γ-mangostin treated cells by DCHDA assay and DiOC₆(3) stain. g-Mangostin induced apoptosis, which in turn mediates cytotoxicity in human MG cells was prevented by the addition of catalase. Naturally derived medicines and herbal therapies are drawing increasing attention in regard to the treatment of many health issues, and this includes the testing of new phytochemicals or nutrients for brain tumor patients. This has led to γ-mangostin being identified as a potential leading compound for the development of an anti-brain tumor agent. Full article

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Open AccessArticle

Pancreatic Lipase Inhibition by C-Glycosidic Flavones Isolated from Eremochloa ophiuroides

by Eun Mi Lee, Seung Sik Lee, Byung Yeoup Chung, Jae-Young Cho, In Chul Lee, So Ra Ahn, Soo Jeung Jang and Tae Hoon Kim

Molecules 2010, 15(11), 8251-8259; https://doi.org/10.3390/molecules15118251 - 16 Nov 2010

Cited by 79 | Viewed by 10461

Abstract

Activity-guided fractionation of a methanolic extract of the leaves of Eremochloa ophiuroides (centipede grass) using a pancreatic lipase inhibitory assay led to the isolation and identification of a new C-glycosidic flavone, luteolin 6-C-b-D-boivinopyranoside (1), as well as eight [...] Read more.

Activity-guided fractionation of a methanolic extract of the leaves of Eremochloa ophiuroides (centipede grass) using a pancreatic lipase inhibitory assay led to the isolation and identification of a new C-glycosidic flavone, luteolin 6-C-b-D-boivinopyranoside (1), as well as eight known compounds. The structures of these compounds were established on the basis of interpretation of their spectroscopic data. Among these isolates, the C-glycosidic flavones 1–5 showed potent inhibitory effects on pancreatic lipase, with IC₅₀ values ranging from 18.5 ± 2.6 to 50.5 ± 3.9 mM. Full article

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Open AccessArticle

Antibacterial Activity of Phytochemicals Isolated from Atractylodes japonica against Methicillin-Resistant Staphylococcus aureus

by Seung-Il Jeong, Seon-Young Kim, Sang-Jun Kim, Byung-Soon Hwang, Tae-Ho Kwon, Kang-Yeol Yu, Seung-Ho Hang, Koji Suzuki and Kang-Ju Kim

Molecules 2010, 15(10), 7395-7402; https://doi.org/10.3390/molecules15107395 - 21 Oct 2010

Cited by 36 | Viewed by 10857

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important problems in communities and hospitals. Therefore, new agents are needed to treat acute oral infections from MRSA. In this study, antibacterial compounds from the roots of Atractylodes japonica ( [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important problems in communities and hospitals. Therefore, new agents are needed to treat acute oral infections from MRSA. In this study, antibacterial compounds from the roots of Atractylodes japonica (A. japonica) were isolated and characterized. The compounds were isolated from the root extracts using HPLC-piloted activity-guided fractionations. Four A. japonica compounds were isolated and identified as atractylenolide III (1), atractylenolide I (2), diacetylatractylodiol [(6E,12E)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate, TDEYA, 3). and (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (TDEA, 4), which was obtained by hydrolysis of TDEYA. The minimum inhibitory concentrations (MICs) was determined in the setting of clinical MRSA isolates. Compound 4 showed anti-MRSA activity with a MIC value of 4-32 μg/mL. The overall results provide promising baseline information for the potential use of the extract of A. japonica as well as some of the isolated compounds in the treatment of bacterial infections. Full article

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2862 KiB

Open AccessArticle

Correlation between Cytotoxic Activities and Reduction Potentials of Heterocyclic Quinones

by Junko Koyama, Izumi Morita and Takao Yamori

Molecules 2010, 15(9), 6559-6569; https://doi.org/10.3390/molecules15096559 - 20 Sep 2010

Cited by 18 | Viewed by 7973

Abstract

To search for possible anti-tumor agents or anti-tumor promoters among natural or synthetic products, we used cyclic voltammetry to determine the reduction-oxidation potentials of heterocyclic quinones in phosphate buffer at pH 7.2. We determined the growth inhibitory- and cytotoxic activities of 12 heterocyclic [...] Read more.

To search for possible anti-tumor agents or anti-tumor promoters among natural or synthetic products, we used cyclic voltammetry to determine the reduction-oxidation potentials of heterocyclic quinones in phosphate buffer at pH 7.2. We determined the growth inhibitory- and cytotoxic activities of 12 heterocyclic quinone anti-tumor agent candidates against a panel of 39 human cancer cell lines (JFCR39). The average concentrations of the heterocyclic quinones required for 50% growth inhibition (GI₅₀) against JFCR39 ranged from 0.045 to 13.2 µM, and the 50% lethal concentration (LC₅₀) against JFCR39 ranged from 0.398 to 77.7 µM. The average values of GI₅₀ or LC₅₀ of the heterocyclic quinones correlated significantly with their reduction potentials. These results suggested that reduction-oxidation potentials could be a useful method for the discovery of novel antitumor agents. Full article

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Open AccessArticle

Effects of Eupatilin and Jaceosidin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes

by Hye Young Ji, Sung Yeon Kim, Dong Kyun Kim, Ji Hyun Jeong and Hye Suk Lee

Molecules 2010, 15(9), 6466-6475; https://doi.org/10.3390/molecules15096466 - 16 Sep 2010

Cited by 33 | Viewed by 11836

Abstract

Eupatilin and jaceosidin are bioactive flavones found in the medicinal herbs of the genus Artemisia. These bioactive flavones exhibit various antioxidant, antiinflammatory, antiallergic, and antitumor activities. The inhibitory potentials of eupatilin and jaceosidin on the activities of seven major human cytochrome P450 [...] Read more.

Eupatilin and jaceosidin are bioactive flavones found in the medicinal herbs of the genus Artemisia. These bioactive flavones exhibit various antioxidant, antiinflammatory, antiallergic, and antitumor activities. The inhibitory potentials of eupatilin and jaceosidin on the activities of seven major human cytochrome P450 enzymes in human liver microsomes were investigated using a cocktail probe assay. Eupatilin and jaceosidin potently inhibited CYP1A2-catalyzed phenacetin O-deethylation with 50% inhibitory concentration (IC₅₀) values of 9.4 mM and 5.3 mM, respectively, and CYP2C9-catalyzed diclofenac 4-hydroxylation with IC₅₀ values of 4.1 mM and 10.2 mM, respectively. Eupatilin and jaceosidin were also found to moderately inhibit CYP2C19-catalyzed [S]-mephenytoin 4¢-hydroxylation, CYP2D6-catalyzed bufuralol 1¢-hydroxylation, and CYP2C8-catalyzed amodiaquine N-deethylation. Kinetic analysis of human liver microsomes showed that eupatilin is a competitive inhibitor of CYP1A2 with a K_i value of 2.3 mM and a mixed-type inhibitor of CYP2C9 with a K_i value of 1.6 mM. Jaceosidin was shown to be a competitive inhibitor of CYP1A2 with a K_i value of 3.8 mM and a mixed-type inhibitor of CYP2C9 with K_i value of 6.4 mM in human liver microsomes. These in vitro results suggest that eupatilin and jaceosidin should be further examined for potential pharmacokinetic drug interactions in vivo due to inhibition of CYP1A2 and CYP2C9. Full article

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