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25 pages, 4114 KiB

Open AccessArticle

Geoherbalism Metabolomic Analysis of Atractylodes lancea (Thunb.) DC. by LC-Triple TOF-MS/MS and GC-MS

by Hailong Qiu, Chenxiao Shan, Chenghao Fei, Ping Xue, Yongyi Zhou, Jiahuan Yuan and Xin Liu

Molecules 2023, 28(16), 5974; https://doi.org/10.3390/molecules28165974 - 9 Aug 2023

Cited by 5 | Viewed by 2105

Abstract

The rhizome of Atractylodes lancea (Thunb.) DC. (AL), called Maocangzhu in Chinese, is a geoherbalism medical herb in Jiangsu Province that is often used in the prescription of traditional Chinese medicine (TCM), such as for the treatment of COVID-19. The landform and climatic [...] Read more.

The rhizome of Atractylodes lancea (Thunb.) DC. (AL), called Maocangzhu in Chinese, is a geoherbalism medical herb in Jiangsu Province that is often used in the prescription of traditional Chinese medicine (TCM), such as for the treatment of COVID-19. The landform and climatic environment of each province varies greatly from south to north, which has an important influence on the chemical constituents in AL. However, there is a lack of research on the significance of its geoherbalism, especially in water-soluble parts other than volatile oil. In this study, eight known compounds were isolated and obtained as reference substances from AL. In addition, liquid chromatography coupled with triple-quadrupole time-of-flight tandem mass spectrometry (LC-triple TOF-MS/MS) and gas chromatography–mass spectrometry (GC-MS) were used to analyze and characterize chemical constituents from different habitats. Moreover, orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to reveal the differential metabolomics in AL from different habitats based on the qualitative information of the chemical constituents. Results showed that a total of 33 constituents from GC-MS and 106 constituents from LC-triple TOF-MS/MS were identified or inferred, including terpenoids, polyacetylenes, and others; meanwhile, the fragmentation pathways of different types of compounds were preliminarily deduced from the fragmentation behavior of the major constituents. According to the variable importance in projection (VIP) and p-values, only one volatile differential metabolite was identified by GC-MS screening: β-eudesmol. Overall, five differential metabolites were identified by LC-triple TOF-MS/MS screening: sucrose, 4(15),11-eudesmadiene; atractylenolide I, 3,5,11-tridecatriene-7,9-diyne-1,2-diacetate, and (3Z,5E,11E)-tridecatriene-7,9-diynyl-1-O-(E)-ferulate. This study provides metabolomic information for the establishment of a comprehensive quality evaluation system for AL. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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17 pages, 4640 KiB

Open AccessArticle

LC-MS Profiling of Kakkonto and Identification of Ephedrine as a Key Component for Its Anti-Glycation Activity

by Kaori Ito, Takashi Kikuchi, Kanako Ikube, Kouharu Otsuki, Kazuo Koike and Wei Li

Molecules 2023, 28(11), 4409; https://doi.org/10.3390/molecules28114409 - 29 May 2023

Viewed by 1595

Abstract

A total of 147 oral Kampo prescriptions, which are used clinically in Japan, were evaluated for their anti-glycation activity. Kakkonto demonstrated significant anti-glycation activity, prompting further analysis of its chemical constituents using LC-MS, which revealed the presence of two alkaloids, fourteen flavonoids, two [...] Read more.

A total of 147 oral Kampo prescriptions, which are used clinically in Japan, were evaluated for their anti-glycation activity. Kakkonto demonstrated significant anti-glycation activity, prompting further analysis of its chemical constituents using LC-MS, which revealed the presence of two alkaloids, fourteen flavonoids, two but-2-enolides, five monoterpenoids, and four triterpenoid glycosides. To identify the components responsible for its anti-glycation activity, the Kakkonto extract was reacted with glyceraldehyde (GA) or methylglyoxal (MGO) and analyzed using LC-MS. In LC-MS analysis of Kakkonto reacted with GA, the peak intensity of ephedrine was attenuated, and three products from ephedrine-scavenging GA were detected. Similarly, LC-MS analysis of Kakkonto reacted with MGO revealed two products from ephedrine reacting with MGO. These results indicated that ephedrine was responsible for the observed anti-glycation activity of Kakkonto. Ephedrae herba extract, which contains ephedrine, also showed strong anti-glycation activity, further supporting ephedrine’s contribution to Kakkonto’s reactive carbonyl species’ scavenging ability and anti-glycation activity. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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12 pages, 2188 KiB

Open AccessArticle

Effect of Eleutheroside E on an MPTP-Induced Parkinson’s Disease Cell Model and Its Mechanism

by Yi Yao, Caiyu Liao, Honghao Qiu, Lishan Liang, Wenying Zheng, Liyan Wu and Fanxin Meng

Molecules 2023, 28(9), 3820; https://doi.org/10.3390/molecules28093820 - 29 Apr 2023

Cited by 4 | Viewed by 1950

Abstract

This research investigated the effects of eleutheroside E (EE) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease cell model and its mechanism. Methods: To create a cell model of Parkinson’s disease, MPTP (2500 μmol/L) was administered to rat adrenal pheochromocytoma cells (PC-12) to produce an [...] Read more.

This research investigated the effects of eleutheroside E (EE) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease cell model and its mechanism. Methods: To create a cell model of Parkinson’s disease, MPTP (2500 μmol/L) was administered to rat adrenal pheochromocytoma cells (PC-12) to produce an MPTP group. Selegiline (50 μmol/L) and MPTP had been administered to the positive group beforehand. The eleutheroside E group was divided into low-, medium-, and high-concentration groups, in which the cells were pretreated with eleutheroside E at concentrations of 100 μmol/L, 300 μmol/L, and 500 μmol/L. Next, MPTP was added to the cells separately. The CCK-8 method was used to measure the cell survival rate. Apart from the CCK-8 method, mitochondrial membrane potential detection, cell reactive oxygen species (ROS) detection, and other methods were also adopted to verify the effect of low, medium, and high concentrations of eleutheroside E on the MPTP-induced cell model. Western blot analysis was used to detect changes in the expression of intracellular proteins CytC, Nrf2, and NQO1 to clarify the mechanism. The results are as follows. Compared with the MPTP group, the survival rates of cells at low, medium, and high concentrations of eleutheroside E all increased. The mitochondrial membrane potential at medium and high concentrations of eleutheroside E increased. The ROS levels at medium and high concentrations of eleutheroside E decreased. Moreover, the apoptosis rate decreased and the expression levels of the intracellular proteins CytC, Nrf2, and NQO1 were upregulated. Conclusion: Eleutheroside E can improve the MPTP-induced apoptosis of PC-12 cells by increasing the mitochondrial membrane potential and reducing the level of intracellular reactive oxygen species (ROS). Moreover, the apoptosis of cells is regulated by the expression of CytC, Nrf2, and NQO1 proteins. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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18 pages, 9484 KiB

Open AccessArticle

Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis

by Song Ang, Jinfeng Liang, Wende Zheng, Zhen Zhang, Jinxuan Li, Zhenping Yan, Wing-Leung Wong, Kun Zhang, Min Chen and Panpan Wu

Molecules 2023, 28(7), 3035; https://doi.org/10.3390/molecules28073035 - 29 Mar 2023

Cited by 2 | Viewed by 1877

Abstract

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 [...] Read more.

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC₅₀ values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 μg/mL, respectively, whereas the LC₅₀ value of MA was 659.34 μg/mL. Structure–activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 μg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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15 pages, 5260 KiB

Open AccessArticle

Antiulcer Activity of Anthraquinone–Flavonoid Complex of Rumex tianschanicus Losinsk

by Gulnaz A. Seitimova, Aksholpan K. Shokan, Tatyana G. Tolstikova, Nataliya A. Zhukova, Dmitriy Yu. Korulkin, Nataliya O. Kudrina, Yuliya A. Litvinenko, Nataliya D. Meduntseva, Nina V. Terletskaya and Timur E. Kulmanov

Molecules 2023, 28(5), 2347; https://doi.org/10.3390/molecules28052347 - 3 Mar 2023

Cited by 7 | Viewed by 2412

Abstract

The composition of an ethanol extract from the roots of Rumex tianschanicus Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The phytochemical composition of the anthraquinone–flavonoid complex from (AFC) R. tianschanicus revealed the presence of [...] Read more.

The composition of an ethanol extract from the roots of Rumex tianschanicus Losinsk of the Trans-Ili Alatau wild flora was studied in order to determine its antiulcer activity. The phytochemical composition of the anthraquinone–flavonoid complex from (AFC) R. tianschanicus revealed the presence of numerous polyphenolic compounds, the most abundant of which are anthraquinones (1.77%), flavonoids (6.95%), and tannins (13.39%). The use of column chromatography (CC) and thin-layer chromatography (TLC) in conjunction with UV, IR, NMR spectroscopy, and mass spectrometry data allowed the researchers to isolate and identify the major components of the anthraquinone–flavonoid complex’s polyphenol fraction: physcion, chrysophanol, emodin, isorhamnetin, quercetin, and myricetin. The gastroprotective effect of the polyphenolic fraction of the anthraquinone–flavonoid complex (AFC) of R. tianschanicus roots was examined in an experimental model of rat gastric ulcer induced by indomethacin. The preventive and therapeutic effect of the anthraquinone–flavonoid complex at a dose of 100 mg/kg was analyzed using intragastric administration per day for 1 to 10 days, followed by a histological examination of stomach tissues. It has been demonstrated that prophylactic and prolonged use of the AFC R. tianschanicus in laboratory animals resulted in significantly less pronounced hemodynamic and desquamative changes in the epithelium of gastric tissues. The acquired results thus offer fresh insight into the anthraquinone and flavonoid metabolite component composition of R. tianschanicus roots, and they imply that the examined extract can be used to develop herbal medicines with antiulcer activity. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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18 pages, 2684 KiB

Open AccessArticle

Discovery of Flavone Derivatives Containing Carboxamide Fragments as Novel Antiviral Agents

by Bobo Zhao, Jiali Wang, Lu Wang, Ziwen Wang and Aidang Lu

Molecules 2023, 28(5), 2179; https://doi.org/10.3390/molecules28052179 - 26 Feb 2023

Cited by 3 | Viewed by 1720

Abstract

Plant virus diseases seriously affect the yield and quality of agricultural products, and their prevention and control are difficult. It is urgent to develop new and efficient antiviral agents. In this work, a series of flavone derivatives containing carboxamide fragments were designed, synthesized, [...] Read more.

Plant virus diseases seriously affect the yield and quality of agricultural products, and their prevention and control are difficult. It is urgent to develop new and efficient antiviral agents. In this work, a series of flavone derivatives containing carboxamide fragments were designed, synthesized, and systematically evaluated for their antiviral activities against tobacco mosaic virus (TMV) on the basis of a structural–diversity–derivation strategy. All the target compounds were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. Most of these derivatives displayed excellent in vivo antiviral activities against TMV, especially 4m (inactivation inhibitory effect, 58%; curative inhibitory effect, 57%; and protection inhibitory effect, 59%), which displayed similar activity to ningnanmycin (inactivation inhibitory effect, 61%; curative inhibitory effect, 57%; and protection inhibitory effect, 58%) at 500 μg mL⁻¹; thus, it emerged as a new lead compound for antiviral research against TMV. Antiviral mechanism research by molecular docking demonstrated that compounds 4m, 5a, and 6b could interact with TMV CP and disturb virus assembly. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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16 pages, 15552 KiB

Open AccessArticle

Chemical Profiling, Bioactive Properties, and Anticancer and Antimicrobial Potential of Juglans regia L. Leaves

by Natalia Żurek, Karolina Pycia, Agata Pawłowska, Leszek Potocki and Ireneusz Tomasz Kapusta

Molecules 2023, 28(4), 1989; https://doi.org/10.3390/molecules28041989 - 20 Feb 2023

Cited by 15 | Viewed by 2895

Abstract

The aim of this study was to assess the biological potential of the polyphenolic fraction isolated from J. regia leaves, collected in the Subcarpathian region (Poland). The phenolic profile was determined using the UPLC-PDA-MS/MS method. Biological activity was determined by evaluating the antioxidant, [...] Read more.

The aim of this study was to assess the biological potential of the polyphenolic fraction isolated from J. regia leaves, collected in the Subcarpathian region (Poland). The phenolic profile was determined using the UPLC-PDA-MS/MS method. Biological activity was determined by evaluating the antioxidant, anticancer, antibacterial, and antifungal effects. Prior to this study, the purified polyphenolic fraction was not been tested in this regard. A total of 40 phenolic compounds (104.28 mg/g dw) were identified, with quercetin 3-O-glucoside and quercetin pentosides dominating. The preparation was characterized by a high ability to chelate iron ions and capture O₂^•− and OH^• radicals (reaching IC₅₀ values of 388.61, 67.78 and 193.29 µg/mL, respectively). As for the anticancer activity, among the six tested cell lines, the preparation reduced the viability of the DLD-1, Caco-2, and MCF-7 lines the most, while in the antibacterial activity, among the seven tested strains, the highest susceptibility has been demonstrated against K. pneumoniae, S. pyogenes, and S. aureus. Depending on the needs, such a preparation can be widely used in the design of functional food and/or the cosmetics industry. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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16 pages, 2949 KiB

Open AccessArticle

A Natural Glucan from Black Bean Inhibits Cancer Cell Proliferation via PI3K-Akt and MAPK Pathway

by Peng Li, Yihua Hu, Lingmin Zhan, Jiaqi He, Jingwu Lu, Chunyan Gao, Weijun Du, Aiqin Yue, Jinzhong Zhao and Wuxia Zhang

Molecules 2023, 28(4), 1971; https://doi.org/10.3390/molecules28041971 - 19 Feb 2023

Cited by 3 | Viewed by 2100

Abstract

A natural α-1,6-glucan named BBWPW was identified from black beans. Cell viability assay showed that BBWPW inhibited the proliferation of different cancer cells, especially HeLa cells. Flow cytometry analysis indicated that BBWPW suppressed the HeLa cell cycle in the G2/M phase. Consistently, RT-PCR [...] Read more.

A natural α-1,6-glucan named BBWPW was identified from black beans. Cell viability assay showed that BBWPW inhibited the proliferation of different cancer cells, especially HeLa cells. Flow cytometry analysis indicated that BBWPW suppressed the HeLa cell cycle in the G2/M phase. Consistently, RT-PCR experiments displayed that BBWPW significantly impacts the expression of four marker genes related to the G2/M phase, including p21, CDK1, Cyclin B1, and Survivin. To explore the molecular mechanism of BBWPW to induce cell cycle arrest, a transcriptome-based target inference approach was utilized to predict the potential upstream pathways of BBWPW and it was found that the PI3K-Akt and MAPK signal pathways had the potential to mediate the effects of BBWPW on the cell cycle. Further experimental tests confirmed that BBWPW increased the expression of BAD and AKT and decreased the expression of mTOR and MKK3. These results suggested that BBWPW could regulate the PI3K-Akt and MAPK pathways to induce cell cycle arrest and ultimately inhibit the proliferation of HeLa cells, providing the potential of the black bean glucan to be a natural anticancer drug. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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13 pages, 1478 KiB

Open AccessArticle

Self-Emulsifying Micellization of Crude Extracts from Apple (Malus domestica cv. Anna), Plum (Prunus domestica cv. Satsuma), and Guava (Psidium guajava L.) Fruits

by Laura A. Calvo-Castro, Andrea Irías-Mata, Daronne Cano-Contreras, Elizabeth Arnáez-Serrano, Randall Chacón-Cerdas, Ricardo Starbird-Pérez, Johan Morales-Sánchez and Carolina Centeno-Cerdas

Molecules 2023, 28(3), 1297; https://doi.org/10.3390/molecules28031297 - 29 Jan 2023

Viewed by 2255

Abstract

Micellar microemulsions are thermodynamically stable self-emulsifying systems that have been used to successfully improve the low oral bioavailability of several bioactive phytochemicals, such as antioxidant polyphenols. However, most studies have reported the micellization of single-compounds or purified chemical fractions; thus, the stability, phytochemical-loading [...] Read more.

Micellar microemulsions are thermodynamically stable self-emulsifying systems that have been used to successfully improve the low oral bioavailability of several bioactive phytochemicals, such as antioxidant polyphenols. However, most studies have reported the micellization of single-compounds or purified chemical fractions; thus, the stability, phytochemical-loading efficiency, and bioactivity of complex crude extracts remain largely unexplored. In this study, we evaluated the effects of micellar emulsification of tropical apple (Malus domestica cv. Anna), plum (Prunus domestica cv. Satsuma), and guava (Psidium guajava L.) extracts regarding particle size and stability, polyphenol-loading efficiency, antioxidant capacity, and cytotoxic activity in human and murine cells. Simple food-grade extraction protocols were implemented to obtain apple, plum, and guava extracts. Total polyphenols, flavonoids, and antioxidant activity (DPPH) were determined in the fruit extracts, and their polyphenol profile was further characterized by liquid chromatography (HPLC-DAD). The dried extracts were mixed into a food-grade, self-emulsifying system, and their cytotoxicity in human and murine cell lines was compared. Our research showed that complex fruit matrixes were successfully emulsified into thermodynamically stable polysorbate-based nanometric micelles with uniform size distribution and consistent pH stability, with potential applications in food and biomedical industries. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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11 pages, 2488 KiB

Open AccessArticle

The Study of Hypoglycemic Activity of 7-Terpenylcoumarins

by Sergey Kuranov, Mariya Marenina, Dmitriy Ivankin, Mikhail Blokhin, Sergey Borisov, Tatyana Khomenko, Olga Luzina, Mikhail Khvostov, Konstantin Volcho, Tatyana Tolstikova and Nariman Salakhutdinov

Molecules 2022, 27(24), 8663; https://doi.org/10.3390/molecules27248663 - 7 Dec 2022

Cited by 3 | Viewed by 1770

Abstract

Natural and synthetic coumarins are often considered privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized. A new approach using the Mitsunobu [...] Read more.

Natural and synthetic coumarins are often considered privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized. A new approach using the Mitsunobu reaction was shown to be effective for the synthesis of target compounds. All of the synthesized compounds were evaluated in an oral glucose tolerance test, and two of them containing geranyl and (-)-myrtenyl substituents showed in vivo hypoglycemic action. A possible mechanism of action of these compounds may include inhibition of DPP IV, which was proved in an in vitro test. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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17 pages, 4321 KiB

Open AccessArticle

Chemical Composition and Antifungal Activity of Zanthoxylum armatum Fruit Essential Oil against Phytophthora capsici

by Jingjing Yang, Qizhi Wang, Linwei Li, Pirui Li, Min Yin, Shu Xu, Yu Chen, Xu Feng and Bi Wang

Molecules 2022, 27(23), 8636; https://doi.org/10.3390/molecules27238636 - 6 Dec 2022

Cited by 5 | Viewed by 2538

Abstract

Pathogenic plant oomycetes cause devastating damage to fruits and vegetables worldwide. Plant essential oils (EOs) are known to be promising candidates for the development of fungicides. In this study, we isolated twelve EOs from Tetradium ruticarpum, Tetradium daniellii, Tetradium fraxinifolium, [...] Read more.

Pathogenic plant oomycetes cause devastating damage to fruits and vegetables worldwide. Plant essential oils (EOs) are known to be promising candidates for the development of fungicides. In this study, we isolated twelve EOs from Tetradium ruticarpum, Tetradium daniellii, Tetradium fraxinifolium, Zanthoxylum armatum, Ruta graveolens, and Citrus medica leaves and fruits. We then investigated their chemical composition and antifungal activity against phytopathogenic oomycetes. Our results demonstrated that Z. armatum fruit essential oil (ZFO) in particular substantially inhibited the mycelial growth of Phytophthora capsici. Similarly, ZFO also strongly suppressed spore production and germination of P. capsici, and the application of ZFO significantly reduced disease symptoms caused by P. capsici in pepper. Furthermore, results from microscopic and biochemical studies indicated that ZFO damaged the ultrastructure and destroyed the membrane integrity of P. capsici, leading to the leakage of the cellular contents and ultimately causing cell death. It was concluded that ZFO could enhance the activities of defense-related enzymes in pepper fruits, which may also be responsible for the inhibition of phytophthora disease. Moreover, linalool and D-limonene were proven to be the primary effective components of ZFO. Our results collectively indicate that ZFO could be a potential candidate for the management of disease caused by P. capsici. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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17 pages, 4523 KiB

Open AccessArticle

Shikonin as a WT1 Inhibitor Promotes Promyeloid Leukemia Cell Differentiation

by Zhenzhen Guo, Luyao Sun, Haojie Xia, Shibin Tian, Mengyue Liu, Jiejie Hou, Jiahuan Li, Haihong Lin and Gangjun Du

Molecules 2022, 27(23), 8264; https://doi.org/10.3390/molecules27238264 - 26 Nov 2022

Cited by 7 | Viewed by 2477

Abstract

This study aims to observe the differentiating effect of shikonin on Wilms’ tumor 1 (WT1)-positive HL-60 cells and investigate the fate of the differentiated leukemia cells. WT1 overexpression unaffected cell viability but promoted resistance to H₂O₂-induced DNA injury and [...] Read more.

This study aims to observe the differentiating effect of shikonin on Wilms’ tumor 1 (WT1)-positive HL-60 cells and investigate the fate of the differentiated leukemia cells. WT1 overexpression unaffected cell viability but promoted resistance to H₂O₂-induced DNA injury and cell apoptosis. The binding of shikonin to the WT1 protein was confirmed by molecular docking and drug affinity reaction target stability (DARTS). Shikonin at the non-cytotoxic concentration could decrease the WT1 protein and simultaneously reduced the CD34 protein and increased the CD11b protein in a dose-dependent manner in normal HL-60 cells but not in WT1-overexpressed HL-60 cells. Shikonin unaffected HL-60 cell viability in 48 h. However, it lasted for 10 days; could attenuate cell proliferation, mitochondrial membrane potential (MMP), and self-renewal; prevent the cell cycle; promote cell apoptosis. In a mouse leukemia model, shikonin could decrease the WT1 protein to prevent leukemia development in a dose-dependent manner. In this study, we also confirmed preliminarily the protein–protein interactions between WT1 and CD34 in molecular docking and CO-IP assay. Our results suggest that: 1. shikonin can down-regulate the WT1 protein level for leukemia differentiation therapy, and 2. the interaction between WT1 and CD34 proteins may be responsible for granulocyte/monocyte immaturity in HL-60 cells. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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16 pages, 3403 KiB

Open AccessArticle

Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction

by Lía S. Valencia-Chan, Neptis Estrada-Alfaro, Jimmy Josué Ceballos-Cruz, Luis W. Torres-Tapia, Sergio R. Peraza-Sánchez and Rosa E. Moo-Puc

Molecules 2022, 27(23), 8263; https://doi.org/10.3390/molecules27238263 - 26 Nov 2022

Cited by 2 | Viewed by 2166

Abstract

Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m [...] Read more.

Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m) caused a decrease in the median inhibitory concentration (IC₅₀) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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11 pages, 1372 KiB

Open AccessArticle

Synthesis and Evaluation of 11-Butyl Matrine Derivatives as Potential Anti-Virus Agents

by Wanjun Ni, Lizhong Wang, Hongjian Song, Yuxiu Liu and Qingmin Wang

Molecules 2022, 27(21), 7563; https://doi.org/10.3390/molecules27217563 - 4 Nov 2022

Cited by 3 | Viewed by 1873

Abstract

Matrine derivatives were reported to have various biological activities, especially the ester, amide or sulfonamide derivatives of matrine deriving from the hydroxyl or carboxyl group at the end of the branch chain after the D ring of matrine is opened. In this work, [...] Read more.

Matrine derivatives were reported to have various biological activities, especially the ester, amide or sulfonamide derivatives of matrine deriving from the hydroxyl or carboxyl group at the end of the branch chain after the D ring of matrine is opened. In this work, to investigate whether moving away all functional groups from the C-11 branch chain could have an impact on the bioactivities, such as anti-tobacco mosaic virus (TMV), insecticidal and fungicidal activities, a variety of N-substituted-11-butyl matrine derivatives were synthesized. The obtained bioassay result showed that most N-substituted-11-butyl matrine derivatives had obviously enhanced anti-TMV activity compared with matrine, especially many compounds had good inhibitory activity close to that of commercialized virucide Ningnanmycin (inhibition rate 55.4, 57.8 ± 1.4, 55.3 ± 0.5 and 60.3 ± 1.2% at 500 μg/mL; 26.1, 29.7 ± 0.2, 24.2 ± 1.0 and 27.0 ± 0.3% at 100 μg/mL, for the in vitro activity, in vivo inactivation, curative and protection activities, respectively). Notably, N-benzoyl (7), N-benzyl (16), and N-cyclohexylmethyl-11-butyl (19) matrine derivatives had higher anti-TMV activity than Ningnanmycin at both 500 and 100 μg/mL for the four test modes, showing high potential as anti-TMV agent. Furthermore, some compounds also showed good fungicidal activity or insecticidal activity. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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15 pages, 2144 KiB

Open AccessArticle

Antihypothyroid Effect of Salidroside

by Nazym K. Korbozova, Nataliya O. Kudrina, Nataliya A. Zhukova, Alexander E. Grazhdannikov, Irina V. Blavachinskaya, Gulnaz A. Seitimova, Timur E. Kulmanov, Tatyana G. Tolstikova and Nina V. Terletskaya

Molecules 2022, 27(21), 7487; https://doi.org/10.3390/molecules27217487 - 2 Nov 2022

Cited by 5 | Viewed by 2155

Abstract

In terms of prevalence, thyroid pathology, associated both with a violation of the gland function and changes in its structure, occupies one of the main places in clinical endocrinology. The problem of developing low-toxic and highly effective herbal preparations for the correction of [...] Read more.

In terms of prevalence, thyroid pathology, associated both with a violation of the gland function and changes in its structure, occupies one of the main places in clinical endocrinology. The problem of developing low-toxic and highly effective herbal preparations for the correction of thyroid hypofunction and its complications is urgent. Salidroside is a glucoside of tyrosol, found mostly in the roots of Rhodiola spp., and has various positive biological activities. The purpose of this study was to study the antihypothyroid potential of salidrosid-containing extract from R. semenovii roots, which was evaluated on a mercazolyl hypothyroidism model. We showed that extract containing salidroside is a safe and effective means of hypothyroidism correction, significantly reducing (p ≤ 0.001) the level of thyroid-stimulating hormone and increasing the level of thyroid hormones. The combined use of R. semenovii extract with potassium iodide enhances the therapeutic effect of the extract by 1.3-times. Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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16 pages, 1553 KiB

Open AccessReview

Amanitins: The Most Poisonous Molecules of the Fungal World

by János Vetter

Molecules 2023, 28(15), 5932; https://doi.org/10.3390/molecules28155932 - 7 Aug 2023

Cited by 9 | Viewed by 4051

Abstract

Among the toxic metabolites of the fungal world, those that, due to their strong biological effect, can seriously (even fatally) damage the life processes of humans (and certain groups of animals) stand out. Amatoxin-containing mushrooms and the poisonings caused by them stand out [...] Read more.

Among the toxic metabolites of the fungal world, those that, due to their strong biological effect, can seriously (even fatally) damage the life processes of humans (and certain groups of animals) stand out. Amatoxin-containing mushrooms and the poisonings caused by them stand out from the higher fungi, the mushrooms. There are already historical data and records about such poisonings, but scientific research on the responsible molecules began in the middle of the last century. The goals of this review work are as follows: presentation of the cosmopolitan mushroom species that produce amanitins (which are known from certain genera of four mushroom families), an overview of the chemical structure and specific properties of amanitins, a summary of the analytical methods applicable to them, a presentation of the “medical history” of poisonings, and a summary of the therapeutic methods used so far. The main responsible molecules (the amanitins) are bicyclic octapeptides, whose structure is characterized by an outer loop and an inner loop (bridge). It follows from the unusual properties of amanitins, especially their extreme stability (against heat, the acidic pH of the medium, and their resistance to human, and animal, digestive enzymes), that they are absorbed almost without hindrance and quickly transported to our vital organs. Adding to the problems is that accidental consumption causes no noticeable symptoms for a few hours (or even 24–36 h) after consumption, but the toxins already damage the metabolism of the target organs and the synthesis of nucleic acid and proteins. The biochemical catastrophe of the cells causes irreversible structural changes, which lead to necrotic damage (in the liver and kidneys) and death. The scientific topicality of the review is due to the recent publication of new data on the probable antidote molecule (ICR: indocyanine green) against amanitins. Further research can provide a new foundation for the therapeutic treatment of poisonings, and the toxicological situation, which currently still poses a deadly threat, could even be tamed into a controllable problem. We also draw attention to the review conclusions, as well as the mycological and social tasks related to amanitin poisonings (prevention of poisonings). Full article

(This article belongs to the Special Issue Natural Substances and Their Derivatives: In Search of New Structures, Activities and Applications)

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