Marine Drugs

23 pages, 2038 KiB

Open AccessArticle

Chromone Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA0220 and Their Antibacterial Activity

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

Mar. Drugs 2018, 16(8), 289; https://doi.org/10.3390/md16080289 - 20 Aug 2018

Cited by 21 | Viewed by 6443

Abstract

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with [...] Read more.

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with thirteen known compounds: β-sitostenone, ergosterol 5,8-endoperoxide, citromycin (1a), 12-methoxycitromycin (1b), myxotrichin D (1d), 12-methoxycitromycetin (1e), anhydrofulvic acid (2a), myxotrichin C (2b), penialidin D (2c), penialidin F (3a), SPF-3059-30 (7), GKK1032B (8) and secalonic acid A (9), from cultures of the marine sponge- associated fungus Penicillium erubescens KUFA0220. Compounds 1a–e, 2a, 3a, 4, 7–9, were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 8 exhibited an in vitro growth inhibition of all Gram-positive bacteria whereas 9 showed growth inhibition of methicillin-resistant Staphyllococus aureus (MRSA). None of the compounds were active against Gram-negative bacteria tested. Full article

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14 pages, 2057 KiB

Open AccessFeature PaperReview

Blueprints for the Next Generation of Bioinspired and Biomimetic Mineralised Composites for Bone Regeneration

by Pamela J. Walsh, Kathryn Fee, Susan A. Clarke, Matthew L. Julius and Fraser J. Buchanan

Mar. Drugs 2018, 16(8), 288; https://doi.org/10.3390/md16080288 - 20 Aug 2018

Cited by 15 | Viewed by 6926

Abstract

Coccolithophores are unicellular marine phytoplankton, which produce intricate, tightly regulated, exoskeleton calcite structures. The formation of biogenic calcite occurs either intracellularly, forming ‘wheel-like’ calcite plates, or extracellularly, forming ‘tiled-like’ plates known as coccoliths. Secreted coccoliths then self-assemble into multiple layers to form the [...] Read more.

Coccolithophores are unicellular marine phytoplankton, which produce intricate, tightly regulated, exoskeleton calcite structures. The formation of biogenic calcite occurs either intracellularly, forming ‘wheel-like’ calcite plates, or extracellularly, forming ‘tiled-like’ plates known as coccoliths. Secreted coccoliths then self-assemble into multiple layers to form the coccosphere, creating a protective wall around the organism. The cell wall hosts a variety of unique species-specific inorganic morphologies that cannot be replicated synthetically. Although biomineralisation has been extensively studied, it is still not fully understood. It is becoming more apparent that biologically controlled mineralisation is still an elusive goal. A key question to address is how nature goes from basic building blocks to the ultrafine, highly organised structures found in coccolithophores. A better understanding of coccolithophore biomineralisation will offer new insight into biomimetic and bioinspired synthesis of advanced, functionalised materials for bone tissue regeneration. The purpose of this review is to spark new interest in biomineralisation and gain new insight into coccolithophores from a material science perspective, drawing on existing knowledge from taxonomists, geologists, palaeontologists and phycologists. Full article

(This article belongs to the Special Issue Marine Organisms for Bone Regeneration)

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14 pages, 2174 KiB

Open AccessArticle

Alkaline Phosphatase Immobilization on New Chitosan Membranes with Mg²⁺ for Biomedical Applications

by Gratiela Teodora Tihan, Roxana Gabriela Zgarian, Elena Berteanu, Daniela Ionita, Georgeta Totea, Catalin Iordachel, Rodica Tatia, Mariana Prodana and Ioana Demetrescu

Mar. Drugs 2018, 16(8), 287; https://doi.org/10.3390/md16080287 - 18 Aug 2018

Cited by 11 | Viewed by 4441

Abstract

In this paper, we present the fabrication and characterization of new chitosan-based membranes while using a new biotechnology for immobilizing alkaline phosphatase (ALP). This technology involved metal ions incorporation to develop new biopolymeric supports. The chemical structure and morphological characteristics of proposed membranes [...] Read more.

In this paper, we present the fabrication and characterization of new chitosan-based membranes while using a new biotechnology for immobilizing alkaline phosphatase (ALP). This technology involved metal ions incorporation to develop new biopolymeric supports. The chemical structure and morphological characteristics of proposed membranes were evaluated by infrared spectroscopy (FT-IR) and the scanning electron microscopy technique (SEM). The inductively coupled plasma mass spectrometry (ICP-MS) evidenced the metal ion release in time. Moreover, the effect of Mg²⁺ on the enzymatic activity and the antibacterial investigations while using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria, hemolysis, and biocompatibility behavior were studied. Immobilizing ALP into the chitosan membranes composition followed by the incorporation of Mg²⁺ led to polymeric supports with enhanced cellular viability when comparing to chitosan-based membranes without Mg²⁺. The results obtained evidenced promising performance in biomedical applications for the new biopolymeric supports that are based on chitosan, ALP, and metal ions. Full article

(This article belongs to the Special Issue Marine Metabolites and Metal Ion Chelation)

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13 pages, 2086 KiB

Open AccessArticle

Anti-Photoaging Effects of Low Molecular-Weight Fucoidan on Ultraviolet B-Irradiated Mice

by Young-In Kim, Won-Seok Oh, Phil Hyun Song, Sungho Yun, Young-Sam Kwon, Young Joon Lee, Sae-Kwang Ku, Chang-Hyun Song and Tae-Ho Oh

Mar. Drugs 2018, 16(8), 286; https://doi.org/10.3390/md16080286 - 18 Aug 2018

Cited by 54 | Viewed by 5745

Abstract

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant [...] Read more.

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm² (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1β release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging. Full article

(This article belongs to the Special Issue Anti-Photoagaing and Photo-Protective Compounds from Marine Organisms)

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9 pages, 1237 KiB

Open AccessCommunication

Isolation of Smenopyrone, a Bis-γ-Pyrone Polypropionate from the Caribbean Sponge Smenospongia aurea

by Germana Esposito, Roberta Teta, Gerardo Della Sala, Joseph R. Pawlik, Alfonso Mangoni and Valeria Costantino

Mar. Drugs 2018, 16(8), 285; https://doi.org/10.3390/md16080285 - 17 Aug 2018

Cited by 10 | Viewed by 4471

Abstract

The organic extract of the Caribbean sponge Smenospongia aurea has been shown to contain an array of novel chlorinated secondary metabolites derived from a mixed PKS-NRPS biogenetic route such as the smenamides. In this paper, we report the presence of a biogenetically different [...] Read more.

The organic extract of the Caribbean sponge Smenospongia aurea has been shown to contain an array of novel chlorinated secondary metabolites derived from a mixed PKS-NRPS biogenetic route such as the smenamides. In this paper, we report the presence of a biogenetically different compound known as smenopyrone, which is a polypropionate containing two γ-pyrone rings. The structure of smenopyrone including its relative and absolute stereochemistry was determined by spectroscopic analysis (NMR, MS, ECD) and supported by a comparison with model compounds from research studies. Pyrone polypropionates are unprecedented in marine sponges but are commonly found in marine mollusks where their biosynthesis by symbiotic bacteria has been hypothesized and at least in one case demonstrated. Since pyrones have recently been recognized as bacterial signaling molecules, we speculate that smenopyrone could mediate inter-kingdom chemical communication between S. aurea and its symbiotic bacteria. Full article

(This article belongs to the Special Issue Quorum Quenching Agents: Exploring Quorum Sensing Interfering Strategies in Marine Bacteria for the Development of Novel Therapeutics)

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10 pages, 4225 KiB

Open AccessArticle

Eutypellenoids A–C, New Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D-1

by Hao-Bing Yu, Xiao-Li Wang, Wei-Heng Xu, Yi-Xin Zhang, Yi-Sen Qian, Jian-Peng Zhang, Xiao-Ling Lu and Xiao-Yu Liu

Mar. Drugs 2018, 16(8), 284; https://doi.org/10.3390/md16080284 - 16 Aug 2018

Cited by 26 | Viewed by 4482

Abstract

Three new pimarane diterpenes, eutypellenoids A–C (1–3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1–3 possessed an uncommon [...] Read more.

Three new pimarane diterpenes, eutypellenoids A–C (1–3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1–3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 μg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candida parapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 μg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC₅₀ value of 3.7 μM. Full article

(This article belongs to the Special Issue Terpenoids from Marine Organisms)

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15 pages, 2565 KiB

Open AccessArticle

Photosynthetic Accumulation of Lutein in Auxenochlorella protothecoides after Heterotrophic Growth

by Yibo Xiao, Xi He, Qi Ma, Yue Lu, Fan Bai, Junbiao Dai and Qingyu Wu

Mar. Drugs 2018, 16(8), 283; https://doi.org/10.3390/md16080283 - 16 Aug 2018

Cited by 40 | Viewed by 4831

Abstract

In order to enhance lutein accumulation and to explain the reasons for the difference in lutein accumulation under photoautotrophic and heterotrophic conditions, different culture modes and the associated transcriptome profiles were investigated in Auxenochlorella protothecoides. The heterotrophic-photoautotrophic transition culture mode was investigated [...] Read more.

In order to enhance lutein accumulation and to explain the reasons for the difference in lutein accumulation under photoautotrophic and heterotrophic conditions, different culture modes and the associated transcriptome profiles were investigated in Auxenochlorella protothecoides. The heterotrophic-photoautotrophic transition culture mode was investigated for lutein accumulation, changing from organic carbon to increase biomass in dark fermentation to irradiation under nitrogen rich conditions. This strategy increased the lutein content 10 times along with chloroplast regeneration and little biomass loss in 48 h. The highest lutein productivity and production in the heterotrophic-photoautotrophic transition culture reached 12.36 mg/L/day and 34.13 mg/L respectively within seven days. Furthermore, compared to the photoautotrophic conditions, most genes involved in lutein biosynthesis and photosystem generation were down-regulated during heterotrophic growth. By contrast, two β-ring hydroxylases were transiently upregulated, while violaxanthin de-epoxidase and zeaxanthin epoxidase were mostly downregulated, which explained the extremely low lutein content of heterotrophic cells. Nevertheless, the lutein proportion in total carotenoids reached nearly 100%. This study is the first to our knowledge to report on a comparative transcriptome analysis of lutein biosynthesis, and it provides a promising strategy to boost lutein production in A. protothecoides. Full article

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9 pages, 794 KiB

Open AccessCommunication

New Ansamycins from the Deep-Sea-Derived Bacterium Ochrobactrum sp. OUCMDZ-2164

by Yaqin Fan, Cong Wang, Liping Wang, Arthit Chairoungdua, Pawinee Piyachaturawat, Peng Fu and Weiming Zhu

Mar. Drugs 2018, 16(8), 282; https://doi.org/10.3390/md16080282 - 15 Aug 2018

Cited by 17 | Viewed by 4435

Abstract

Two new ansamycins, trienomycins H (1) and I (2), together with the known trienomycinol (3), were isolated from the fermentation broth of the deep-sea-derived bacterium Ochrobactrum sp. OUCMDZ-2164. Their structures, including their absolute configurations, were elucidated based [...] Read more.

Two new ansamycins, trienomycins H (1) and I (2), together with the known trienomycinol (3), were isolated from the fermentation broth of the deep-sea-derived bacterium Ochrobactrum sp. OUCMDZ-2164. Their structures, including their absolute configurations, were elucidated based on spectroscopic analyses, ECD spectra, and Marfey’s method. Compound 1 exhibited cytotoxic effects on A549 and K562 cell lines with IC₅₀ values of 15 and 23 μM, respectively. Full article

(This article belongs to the Special Issue Marine Bacteria as Sources of Bioactive Compounds)

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13 pages, 2763 KiB

Open AccessArticle

Structure and Bioactivity Screening of a Low Molecular Weight Ulvan from the Green Alga Ulothrix flacca

by Peipei Li, Songsong Wen, Kunlai Sun, Yuqin Zhao and Yin Chen

Mar. Drugs 2018, 16(8), 281; https://doi.org/10.3390/md16080281 - 15 Aug 2018

Cited by 21 | Viewed by 5717

Abstract

A water-soluble low molecular–weight polysaccharide named UP2-1 was isolated and purified from the marine green algae Ulothrix flacca using ion-exchange and size-exclusion chromatography. Composition and characteristics analyses showed that UP2-1 was a sulfated glucuronorhamnan consisting of rhamnose and glucuronic acid in a ratio [...] Read more.

A water-soluble low molecular–weight polysaccharide named UP2-1 was isolated and purified from the marine green algae Ulothrix flacca using ion-exchange and size-exclusion chromatography. Composition and characteristics analyses showed that UP2-1 was a sulfated glucuronorhamnan consisting of rhamnose and glucuronic acid in a ratio of 2:1 with 21% sulfate content and a molecular weight of 5.0 kDa. Structural properties were determined using desulfation and methylation analyses combined with infrared spectrum (IR), gas chromatography-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR). The results showed that UP2-1 was a type of ulvan composed of alternate 4-linked-α-L-rhamnose residues (→4)-α-L-Rha(1→) and 4-linked-β-D-glucouronoc acid residues. The sulfate groups were mainly present in the O-3 position of →4)-α-L-Rha(1→. Most (70%) of the rhamnose was sulfated. UP2-1 also had a small amount of →4)-α-L-Rha(1→ branch at the O-2 position of the →4)-α-L-Rha(1→. UP2-1 exhibited significant anticoagulant and immunomodulating activity in vitro. This study demonstrated that the green algae Ulothrix flacca, which is used as a food and traditional marine herb in China, could also be considered as a source of bioactive ulvan. Full article

(This article belongs to the Special Issue Discovery and Application of Macroalgae-Derived Natural Products)

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13 pages, 1364 KiB

Open AccessArticle

Perylenequione Derivatives with Anticancer Activities Isolated from the Marine Sponge-Derived Fungus, Alternaria sp. SCSIO41014

by Xiaoyan Pang, Xiuping Lin, Pei Wang, Xuefeng Zhou, Bin Yang, Junfeng Wang and Yonghong Liu

Mar. Drugs 2018, 16(8), 280; https://doi.org/10.3390/md16080280 - 14 Aug 2018

Cited by 45 | Viewed by 4989

Abstract

Seven new secondary metabolites classified as two perylenequinone derivatives (1 and 2), an altenusin derivative (3), two phthalide racemates (4 and 5), and two phenol derivatives (6 and 7), along with twenty-one known compounds ( [...] Read more.

Seven new secondary metabolites classified as two perylenequinone derivatives (1 and 2), an altenusin derivative (3), two phthalide racemates (4 and 5), and two phenol derivatives (6 and 7), along with twenty-one known compounds (8–28) were isolated from cultures of the sponge-derived fungus, Alternaria sp. SCSIO41014. The structures and absolute configurations of these new compounds (1–7) were determined by spectroscopic analysis, X-ray single crystal diffraction, chiral-phase HPLC separation, and comparison of ECD spectra to calculations. Altertoxin VII (1) is the first example possessing a novel 4,8-dihydroxy-substituted perylenequinone derivative, while the phenolic hydroxy groups have commonly always substituted at C-4 and C-9. Compound 1 exhibited cytotoxic activities against human erythroleukemia (K562), human gastric carcinoma cells (SGC-7901), and hepatocellular carcinoma cells (BEL-7402) with IC₅₀ values of 26.58 ± 0.80, 8.75 ± 0.13, and 13.11 ± 0.95 μg/mL, respectively. Compound 11 showed selectively cytotoxic activity against K562, with an IC₅₀ value of 19.67 ± 0.19 μg/mL. Compound 25 displayed moderate inhibitory activity against Staphylococcus aureus with an MIC value of 31.25 μg/mL. Full article

(This article belongs to the Special Issue Natural Products from Marine Fungi)

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31 pages, 393 KiB

Open AccessReview

Current Screening Methodologies in Drug Discovery for Selected Human Diseases

by Olga Maria Lage, María C. Ramos, Rita Calisto, Eduarda Almeida, Vitor Vasconcelos and Francisca Vicente

Mar. Drugs 2018, 16(8), 279; https://doi.org/10.3390/md16080279 - 14 Aug 2018

Cited by 87 | Viewed by 10780

Abstract

The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of [...] Read more.

The increase of many deadly diseases like infections by multidrug-resistant bacteria implies re-inventing the wheel on drug discovery. A better comprehension of the metabolisms and regulation of diseases, the increase in knowledge based on the study of disease-born microorganisms’ genomes, the development of more representative disease models and improvement of techniques, technologies, and computation applied to biology are advances that will foster drug discovery in upcoming years. In this paper, several aspects of current methodologies for drug discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm and antiquorum sensing, anticancer and neuroprotectors are considered. For drug discovery, two different complementary approaches can be applied: classical pharmacology, also known as phenotypic drug discovery, which is the historical basis of drug discovery, and reverse pharmacology, also designated target-based drug discovery. Screening methods based on phenotypic drug discovery have been used to discover new natural products mainly from terrestrial origin. Examples of the discovery of marine natural products are provided. A section on future trends provides a comprehensive overview on recent advances that will foster the pharmaceutical industry. Full article

(This article belongs to the Special Issue Bioassay-Guided Isolation of Marine Natural Products for Drug Discovery)

13 pages, 2605 KiB

Open AccessArticle

by Chia-Hua Wu, Chih-Hua Chao, Tzu-Zin Huang, Chiung-Yao Huang, Tsong-Long Hwang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2018, 16(8), 278; https://doi.org/10.3390/md16080278 - 9 Aug 2018

Cited by 25 | Viewed by 5230

Abstract

Five new cembranoid-related diterpenoids, namely, flexibilisins D and E (1 and 2), secoflexibilisolides A and B (3 and 4), and flexibilisolide H (5), along with nine known compounds (6–14), were isolated from the [...] Read more.

Five new cembranoid-related diterpenoids, namely, flexibilisins D and E (1 and 2), secoflexibilisolides A and B (3 and 4), and flexibilisolide H (5), along with nine known compounds (6–14), were isolated from the soft coral Sinularia flexibilis. Their structures were established by extensive spectral analysis. Compound 3 possesses an unusual skeleton that could be biogenetically derived from cembranoids. The cytotoxicity and anti-inflammatory activities of the isolates were investigated, and the results showed that dehydrosinulariolide (7) and 11-epi-sinulariolide acetate (8) exhibited cytotoxicity toward a limited panel of cancer cell lines and 14-deoxycrassin (9) displayed anti-inflammatory activity by inhibition of superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophils. Full article

(This article belongs to the Special Issue Marine Natural Products Discovery: In Memory of Late Prof. Tatsuo Higa)

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13 pages, 3377 KiB

Open AccessArticle

Green Synthesis of Gold Nanoparticles Using Carrageenan Oligosaccharide and Their In Vitro Antitumor Activity

by Xiangyan Chen, Xia Zhao, Yanyun Gao, Jiaqi Yin, Mingyue Bai and Fahe Wang

Mar. Drugs 2018, 16(8), 277; https://doi.org/10.3390/md16080277 - 7 Aug 2018

Cited by 78 | Viewed by 6855

Abstract

Gold nanoparticles (AuNPs) have been widely used in catalysis, photothermal therapy, and targeted drug delivery. Carrageenan oligosaccharide (CAO) derived from marine red algae was used as a reducing and capping agent to obtain AuNPs by an eco-friendly, efficient, and simple synthetic route for [...] Read more.

Gold nanoparticles (AuNPs) have been widely used in catalysis, photothermal therapy, and targeted drug delivery. Carrageenan oligosaccharide (CAO) derived from marine red algae was used as a reducing and capping agent to obtain AuNPs by an eco-friendly, efficient, and simple synthetic route for the first time. The synthetic conditions of AuNPs were optimized by response surface methodology (RSM), and the CAO-AuNPs obtained were demonstrated to be ellipsoidal, stable and crystalline by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The CAO-AuNPs showed localized surface plasmon resonance (LSPR) oscillation at about 530 nm with a mean diameter of 35 ± 8 nm. The zeta potential of CAO-AuNPs was around −20 mV, which was related to the negatively charged CAO around AuNPs. The CAO-AuNPs exhibited significant cytotoxic activities to HCT-116 and MDA-MB-231 cells, which could be a promising nanomaterial for drug delivery. Full article

(This article belongs to the Special Issue Marine Drugs and Nanomedicine)

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17 pages, 3348 KiB

Open AccessArticle

New Cembranoids and a Biscembranoid Peroxide from the Soft Coral Sarcophyton cherbonnieri

by Chia-Chi Peng, Chiung-Yao Huang, Atallah F. Ahmed, Tsong-Long Hwang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2018, 16(8), 276; https://doi.org/10.3390/md16080276 - 6 Aug 2018

Cited by 22 | Viewed by 4791

Abstract

Six new cembranoids, cherbonolides A−E (1–5) and bischerbolide peroxide (6), along with one known cembranoid, isosarcophine (7), were isolated from the Formosan soft coral Sarcophyton cherbonnieri. The structures of these compounds were elucidated by [...] Read more.

Six new cembranoids, cherbonolides A−E (1–5) and bischerbolide peroxide (6), along with one known cembranoid, isosarcophine (7), were isolated from the Formosan soft coral Sarcophyton cherbonnieri. The structures of these compounds were elucidated by detailed spectroscopic analysis and chemical methods. Compound 6 was discovered to be the first example of a molecular skeleton formed from two cembranoids connected by a peroxide group. Compounds 1–7 were shown to have the ability of inhibiting the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophils. Full article

(This article belongs to the Special Issue Terpenoids from Marine Organisms)

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9 pages, 867 KiB

Open AccessArticle

Degradation of Fucoxanthin to Elucidate the Relationship between the Fucoxanthin Molecular Structure and Its Antiproliferative Effect on Caco-2 Cells

by Shiro Komba, Eiichi Kotake-Nara and Wakako Tsuzuki

Mar. Drugs 2018, 16(8), 275; https://doi.org/10.3390/md16080275 - 6 Aug 2018

Cited by 24 | Viewed by 4432

Abstract

Fucoxanthin has an antiproliferative effect on cancer cells, but its detailed structure–activity correlation has not yet been elucidated. To elucidate this correlation, fucoxanthin was degraded by ozonolysis. The degraded compounds of fucoxanthin obtained by ozonolysis were purified by HPLC and analyzed by NMR. [...] Read more.

Fucoxanthin has an antiproliferative effect on cancer cells, but its detailed structure–activity correlation has not yet been elucidated. To elucidate this correlation, fucoxanthin was degraded by ozonolysis. The degraded compounds of fucoxanthin obtained by ozonolysis were purified by HPLC and analyzed by NMR. The polyene chain of fucoxanthin was cleaved by ozonolysis, and the fucoxanthin was divided into two types of cyclohexyl derivatives, one with a β,γ-epoxy ketone group and the other with an allenic bond. In order to elucidate the structure–activity correlation, Caco-2 cells (human colorectal carcinoma) were treated with fucoxanthin degradation compounds. It was found that the entire structure of fucoxanthin is not essential for its antiproliferative effect and that even a partial structure exerts this effect. Full article

(This article belongs to the Special Issue Marine Carotenoids)

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15 pages, 1194 KiB

Open AccessArticle

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

by Anna Carbone, Barbara Parrino, Maria Grazia Cusimano, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Domenico Schillaci, Girolamo Cirrincione, Patrizia Diana and Stella Cascioferro

Mar. Drugs 2018, 16(8), 274; https://doi.org/10.3390/md16080274 - 4 Aug 2018

Cited by 39 | Viewed by 4679

Abstract

New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity [...] Read more.

New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC₅₀ values against Staphylococcus aureus ATCC 25923, ranging from 0.40–2.03 µM. The new compounds showed a typical anti-virulence profile, being able to inhibit the biofilm formation without affecting the microbial growth in the planktonic form. Full article

(This article belongs to the Special Issue New Strategies to Counteract Antibiotic Resistance Mechanisms)

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25 pages, 45158 KiB

Open AccessReview

Chitosan-Based Composite Materials for Prospective Hemostatic Applications

by Zhang Hu, Dong-Ying Zhang, Si-Tong Lu, Pu-Wang Li and Si-Dong Li

Mar. Drugs 2018, 16(8), 273; https://doi.org/10.3390/md16080273 - 4 Aug 2018

Cited by 214 | Viewed by 16075

Abstract

Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the [...] Read more.

Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the food industry and cosmetics. The excellent hemostatic properties of CS have been extensively studied. As a result, chitosan-based composite hemostatic materials have been emerging. In this review, the hemostatic mechanism of chitosan is briefly discussed, and then the progress of research on chitosan-based composite hemostatic materials with multiple forms such as films, sponges, hydrogels, particles and fibers are introduced. Finally, future perspectives of chitosan-based composite hemostatic materials are given. The objective of this review is to provide a reference for further research and development of effective hemostatic materials. Full article

(This article belongs to the Special Issue Marine Biodegradable Polymers)

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16 pages, 2568 KiB

Open AccessArticle

Chemical Mutagenesis and Fluorescence-Based High-Throughput Screening for Enhanced Accumulation of Carotenoids in a Model Marine Diatom Phaeodactylum tricornutum

by Zhiqian Yi, Yixi Su, Maonian Xu, Andreas Bergmann, Saevar Ingthorsson, Ottar Rolfsson, Kourosh Salehi-Ashtiani, Sigurdur Brynjolfsson and Weiqi Fu

Mar. Drugs 2018, 16(8), 272; https://doi.org/10.3390/md16080272 - 4 Aug 2018

Cited by 39 | Viewed by 8830

Abstract

Diatoms are a major group of unicellular algae that are rich in lipids and carotenoids. However, sustained research efforts are needed to improve the strain performance for high product yields towards commercialization. In this study, we generated a number of mutants of the [...] Read more.

Diatoms are a major group of unicellular algae that are rich in lipids and carotenoids. However, sustained research efforts are needed to improve the strain performance for high product yields towards commercialization. In this study, we generated a number of mutants of the model diatom Phaeodactylum tricornutum, a cosmopolitan species that has also been found in Nordic region, using the chemical mutagens ethyl methanesulfonate (EMS) and N-methyl-N′-nitro-N-nitrosoguanidine (NTG). We found that both chlorophyll a and neutral lipids had a significant correlation with carotenoid content and these correlations were better during exponential growth than in the stationary growth phase. Then, we studied P. tricornutum common metabolic pathways and analyzed correlated enzymatic reactions between fucoxanthin synthesis and pigmentation or lipid metabolism through a genome-scale metabolic model. The integration of the computational results with liquid chromatography-mass spectrometry data revealed key compounds underlying the correlative metabolic pathways. Approximately 1000 strains were screened using fluorescence-based high-throughput method and five mutants selected had 33% or higher total carotenoids than the wild type, in which four strains remained stable in the long term and the top mutant exhibited an increase of 69.3% in fucoxanthin content compared to the wild type. The platform described in this study may be applied to the screening of other high performing diatom strains for industrial applications. Full article

(This article belongs to the Special Issue Chilling Allelochemicals: Natural Products and Bioactivities from Polar and Sub-Polar Latitudes)

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13 pages, 2798 KiB

Open AccessArticle

Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure–Activity Relationship

by Jianpeng Li, Zunying Liu, Yuanhui Zhao, Xiaojie Zhu, Rilei Yu, Shiyuan Dong and Haohao Wu

Mar. Drugs 2018, 16(8), 271; https://doi.org/10.3390/md16080271 - 4 Aug 2018

Cited by 44 | Viewed by 5828

Abstract

Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from [...] Read more.

Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline (w/w, proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates. Among the modified hydrolysates, two novel efficient ACE-inhibitory peptides, which are namely PNVA and PNLG, were purified and identified by a sequential approach combining a sephadex G-15 gel column, reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), before we conducted confirmatory studies with synthetic peptides. The ACE-inhibitory activity assay showed that PNVA and PNLG exhibited lower IC₅₀ values of 8.18 ± 0.24 and 13.16 ± 0.39 μM than their corresponding truncated analogs (NVA and NLG), respectively. Molecular docking showed that PNVA and PNLG formed a larger number of hydrogen bonds with ACE than NVA and NLG, while the proline at the N-terminal of peptides can affect the orientation of the binding site of ACE. The method developed in this study may potentially be applied to prepare efficient ACE-inhibitory peptides, which may play a key role in hypertension management. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential)

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8 pages, 1294 KiB

Open AccessArticle

First Evidence of Dehydroabietic Acid Production by a Marine Phototrophic Gammaproteobacterium, the Purple Sulfur Bacterium Allochromatium vinosum MT86

by Johannes F. Imhoff, Mingshuang Sun, Jutta Wiese, Marcus Tank and Axel Zeeck

Mar. Drugs 2018, 16(8), 270; https://doi.org/10.3390/md16080270 - 4 Aug 2018

Cited by 2 | Viewed by 3741

Abstract

The production of secondary metabolites by a new isolate of the purple sulfur bacterium Allochromatium vinosum, which had shown antibiotic activities during a preliminary study, revealed the production of several metabolites. Growth conditions suitable for the production of one of the compounds [...] Read more.

The production of secondary metabolites by a new isolate of the purple sulfur bacterium Allochromatium vinosum, which had shown antibiotic activities during a preliminary study, revealed the production of several metabolites. Growth conditions suitable for the production of one of the compounds shown in the metabolite profile were established and compound 1 was purified. The molecular formula of compound 1 (C₂₀H₂₈O₂) was determined by high resolution mass spectra, and its chemical structure by means of spectroscopic methods. The evaluation of these data revealed that the structure of the compound was identical to dehydroabietic acid, a compound known to be characteristically produced by conifer trees, but so far not known from bacteria, except cyanobacteria. The purified substance showed weak antibiotic activities against Bacillus subtilis and Staphylococcus lentus with IC₅₀ values of 70.5 µM (±2.9) and 57.0 µM (±3.3), respectively. Full article

(This article belongs to the Special Issue Bioprospecting of Marine Microorganisms)

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14 pages, 5384 KiB

Open AccessArticle

Marine Collagen/Apatite Composite Scaffolds Envisaging Hard Tissue Applications

by Gabriela S. Diogo, Estefania L. López-Senra, Rogério P. Pirraco, Raphael F. Canadas, Emanuel M. Fernandes, Julia Serra, Ricardo I. Pérez-Martín, Carmen G. Sotelo, Alexandra P. Marques, Pio González, Joana Moreira-Silva, Tiago H. Silva and Rui L. Reis

Mar. Drugs 2018, 16(8), 269; https://doi.org/10.3390/md16080269 - 3 Aug 2018

Cited by 50 | Viewed by 7258

Abstract

The high prevalence of bone defects has become a worldwide problem. Despite the significant amount of research on the subject, the available therapeutic solutions lack efficiency. Autografts, the most commonly used approaches to treat bone defects, have limitations such as donor site morbidity, [...] Read more.

The high prevalence of bone defects has become a worldwide problem. Despite the significant amount of research on the subject, the available therapeutic solutions lack efficiency. Autografts, the most commonly used approaches to treat bone defects, have limitations such as donor site morbidity, pain and lack of donor site. Marine resources emerge as an attractive alternative to extract bioactive compounds for further use in bone tissue-engineering approaches. On one hand they can be isolated from by-products, at low cost, creating value from products that are considered waste for the fish transformation industry. One the other hand, religious constraints will be avoided. We isolated two marine origin materials, collagen from shark skin (Prionace glauca) and calcium phosphates from the teeth of two different shark species (Prionace glauca and Isurus oxyrinchus), and further proposed to mix them to produce 3D composite structures for hard tissue applications. Two crosslinking agents, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-Hydroxysuccinimide (EDC/NHS) and hexamethylene diisocyanate (HMDI), were tested to enhance the scaffolds’ properties, with EDC/NHS resulting in better properties. The characterization of the structures showed that the developed composites could support attachment and proliferation of osteoblast-like cells. A promising scaffold for the engineering of bone tissue is thus proposed, based on a strategy of marine by-products valorisation. Full article

(This article belongs to the Special Issue Marine Organisms for Bone Regeneration)

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17 pages, 3365 KiB

Open AccessArticle

Targeted Isolation of Tsitsikammamines from the Antarctic Deep-Sea Sponge Latrunculia biformis by Molecular Networking and Anticancer Activity

by Fengjie Li, Dorte Janussen, Christian Peifer, Ignacio Pérez-Victoria and Deniz Tasdemir

Mar. Drugs 2018, 16(8), 268; https://doi.org/10.3390/md16080268 - 2 Aug 2018

Cited by 23 | Viewed by 6179

Abstract

The Antarctic deep-sea sponge Latrunculia (Latrunculia) biformis Kirkpatrick, 1908 (Class Demospongiae Sollas, Order Poecilosclerida Topsent, Latrunculiidae Topsent) was selected for chemical analyses due to its potent anticancer activity. Metabolomic analysis of its crude extract by HRMS/MS-based molecular networking showed the presence [...] Read more.

The Antarctic deep-sea sponge Latrunculia (Latrunculia) biformis Kirkpatrick, 1908 (Class Demospongiae Sollas, Order Poecilosclerida Topsent, Latrunculiidae Topsent) was selected for chemical analyses due to its potent anticancer activity. Metabolomic analysis of its crude extract by HRMS/MS-based molecular networking showed the presence of several clusters of pyrroloiminoquinone alkaloids, i.e., discorhabdin and epinardin-type brominated pyridopyrroloquinolines and tsitsikammamines, the non-brominated bis-pyrroloiminoquinones. Molecular networking approach combined with a bioactivity-guided isolation led to the targeted isolation of the known pyrroloiminoquinone tsitsikammamine A (1) and its new analog 16,17-dehydrotsitsikammamine A (2). The chemical structures of the compounds 1 and 2 were elucidated by spectroscopic analysis (one-dimensional (1D) and two-dimensional (2D) NMR, HR-ESIMS). Due to minute amounts, molecular modeling and docking was used to assess potential affinities to potential targets of the isolated compounds, including DNA intercalation, topoisomerase I-II, and indoleamine 2,3-dioxygenase enzymes. Tsitsikammamines represent a small class of pyrroloiminoquinone alkaloids that have only previously been reported from the South African sponge genus Tsitsikamma Samaai & Kelly and an Australian species of the sponge genus Zyzzya de Laubenfels. This is the first report of tsitsikammamines from the genus Latrunculia du Bocage and the successful application of molecular networking in the identification of comprehensive chemical inventory of L.biformis followed by targeted isolation of new molecules. This study highlights the high productivity of secondary metabolites of Latrunculia sponges and may shed new light on their biosynthetic origin and chemotaxonomy. Full article

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14 pages, 992 KiB

Open AccessArticle

Orally Administered Phlorotannins from Eisenia arborea Suppress Chemical Mediator Release and Cyclooxygenase-2 Signaling to Alleviate Mouse Ear Swelling

by Yoshimasa Sugiura, Masakatsu Usui, Hirotaka Katsuzaki, Kunio Imai, Makoto Kakinuma, Hideomi Amano and Masaaki Miyata

Mar. Drugs 2018, 16(8), 267; https://doi.org/10.3390/md16080267 - 2 Aug 2018

Cited by 39 | Viewed by 4853

Abstract

Phlorotannin is the collective term for polyphenols derived from brown algae belonging to the genera Ascopyllum, Ecklonia, Eisenia, Fucus and Sargassum etc. Since the incidence of allergies is currently increasing in the world, there is a focus on phlorotannins having [...] Read more.

Phlorotannin is the collective term for polyphenols derived from brown algae belonging to the genera Ascopyllum, Ecklonia, Eisenia, Fucus and Sargassum etc. Since the incidence of allergies is currently increasing in the world, there is a focus on phlorotannins having anti-allergic and anti-inflammatory effects. In this study, six purified phlorotannins (eckol; 6,6′-bieckol; 6,8′-bieckol; 8,8′-bieckol; phlorofucofuroeckol (PFF)-A and PFF-B) from Eisenia arborea, orally administered to mice, were examined for their suppression effects on ear swelling. In considering the suppression, we also examined whether the phlorotannins suppressed release of chemical mediators (histamine, leukotriene B₄ and prostaglandin E₂), and mRNA expression and/or the activity of cyclooxygenase-2 (COX-2), using RBL-2H3 cells, a cultured mast cell model. Results showed that the phlorotnannins exhibited suppression effects in all experiments, with 6,8′-bieckol, 8,8′-bieckol and PFF-A showing the strongest of these effects. In conclusion, orally administered phlorotannins suppress mouse ear swelling, and this mechanism apparently involves suppression of chemical mediator release and COX-2 mRNA expression or activity. This is the first report of the anti-allergic effects of the orally administered purified phlorotannins in vivo. Phlorotannins show potential for use in functional foods or drugs. Full article

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9 pages, 6191 KiB

Open AccessArticle

Halogenated and Nonhalogenated Metabolites from the Marine-Alga-Endophytic Fungus Trichoderma asperellum cf44-2

by Yin-Ping Song, Feng-Ping Miao, Sheng-Tao Fang, Xiu-Li Yin and Nai-Yun Ji

Mar. Drugs 2018, 16(8), 266; https://doi.org/10.3390/md16080266 - 2 Aug 2018

Cited by 42 | Viewed by 4447

Abstract

One new bisabolane sesquiterpene, bisabolan-1,10,11-triol (1), one new norbisabolane sesquiterpene, 12-nor-11-acetoxybisabolen-3,6,7-triol (2), two new naturally occurring monoterpenes, (7S)- and (7R)-1-hydroxy-3-p-menthen-9-oic acids (3 and 4), one new naturally occurring trichodenone, dechlorotrichodenone C [...] Read more.

One new bisabolane sesquiterpene, bisabolan-1,10,11-triol (1), one new norbisabolane sesquiterpene, 12-nor-11-acetoxybisabolen-3,6,7-triol (2), two new naturally occurring monoterpenes, (7S)- and (7R)-1-hydroxy-3-p-menthen-9-oic acids (3 and 4), one new naturally occurring trichodenone, dechlorotrichodenone C (5), one new chlorine-containing trichodenone, 3-hydroxytrichodenone C (6), one new diketopiperazine, methylcordysinin A (7), and one new naturally occurring oxazole derivative, 4-oxazolepropanoic acid (8), were isolated from the culture of a marine brown alga-endophytic strain (cf44-2) of Trichoderma asperellum. Their structures and relative configurations were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 3–6 were assigned by analysis of the ECD spectra aided by quantum chemical computations. Compounds 1, 2, 5, and 6 showed growth inhibition of some marine phytoplankton species and pathogenic bacteria. Full article

(This article belongs to the Special Issue Marine Natural Products from Symbiotic Ecosystems)

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28 pages, 3083 KiB

Open AccessReview

Secondary Metabolites and Biological Activity of Invasive Macroalgae of Southern Europe

by Patrícia Máximo, Luísa M. Ferreira, Paula Branco, Pedro Lima and Ana Lourenço

Mar. Drugs 2018, 16(8), 265; https://doi.org/10.3390/md16080265 - 2 Aug 2018

Cited by 50 | Viewed by 6297

Abstract

In this review a brief description of the invasive phenomena associated with algae and its consequences on the ecosystem are presented. Three examples of invasive algae of Southern Europe, belonging to Rodophyta, Chlorophyta, and Phaeophyta, were selected, and a brief [...] Read more.

In this review a brief description of the invasive phenomena associated with algae and its consequences on the ecosystem are presented. Three examples of invasive algae of Southern Europe, belonging to Rodophyta, Chlorophyta, and Phaeophyta, were selected, and a brief description of each genus is presented. A full description of their secondary metabolites and biological activity is given and a summary of the biological activity of extracts is also included. In Asparagopsis we encounter mainly halogenated compounds. From Caulerpa, several terpenoids and alkaloids were isolated, while in Sargassum, meroterpenoids prevail. Full article

(This article belongs to the Special Issue Progress on Marine Natural Products as Lead Compounds)

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15 pages, 3699 KiB

Open AccessArticle

Sargassum Fusiforme Polysaccharide SFP-F2 Activates the NF-κB Signaling Pathway via CD14/IKK and P38 Axes in RAW264.7 Cells

by Liujun Chen, Peichao Chen, Jian Liu, Chenxi Hu, Shanshan Yang, Dan He, Ping Yu, Mingjiang Wu and Xu Zhang

Mar. Drugs 2018, 16(8), 264; https://doi.org/10.3390/md16080264 - 1 Aug 2018

Cited by 32 | Viewed by 5475

Abstract

Sargassum fusifrome is considered a “longevity vegetable” in Asia. Sargassum fusifrome polysaccharides exhibit numerous biological activities, specially, the modulation of immune response via the NF-κB signaling pathway. However, the precise mechanisms by which these polysaccharides modulate the immune response through the NF-κB signaling [...] Read more.

Sargassum fusifrome is considered a “longevity vegetable” in Asia. Sargassum fusifrome polysaccharides exhibit numerous biological activities, specially, the modulation of immune response via the NF-κB signaling pathway. However, the precise mechanisms by which these polysaccharides modulate the immune response through the NF-κB signaling pathway have not been elucidated. In this study, we purified and characterized a novel fraction of Sargassum fusifrome polysaccharide and named it SFP-F2. SFP-F2 significantly upregulated the production of the cytokines TNF-α, IL-1β and IL-6 in RAW264.7 cells. It also activated the NF-κB signaling pathway. Data obtained from experiments carried out with specific inhibitors (PDTC, BAY 11-7082, IKK16 and SB203580) suggested that SFP-F2 activated the NF-κB signaling pathway via CD14/IKK and P38 axes. SFP-F2 could therefore potentially exert an immune-enhancement effect through inducing the CD14/IKK/NF-κB and P38/NF-κB signaling pathways. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Plankton)

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12 pages, 504 KiB

Open AccessArticle

The Protective Effects of Clams on Hypercholesterolemia in Late-Stage Triple-Transgenic Alzheimer’s Diseased Mice Hearts

by You-Liang Hsieh, Hsu-Ju Teng, Yen-Hung Yeh, Cheng-Hong Hsieh and Chih-Yang Huang

Mar. Drugs 2018, 16(8), 263; https://doi.org/10.3390/md16080263 - 1 Aug 2018

Cited by 5 | Viewed by 3790

Abstract

To investigate a high cholesterol diet in Alzheimer’s disease (AD) mice, they were fed with (2% cholesterol) in five groups with a control group, AD mice group, AD mice plus Meretrix lusoria group, AD mice plus Geloina eros group, and, AD mice plus [...] Read more.

To investigate a high cholesterol diet in Alzheimer’s disease (AD) mice, they were fed with (2% cholesterol) in five groups with a control group, AD mice group, AD mice plus Meretrix lusoria group, AD mice plus Geloina eros group, and, AD mice plus Corbicula fluminea group for three months, and treated with the fatty acid profiles of clams by gas chromatography (GC). The results showed that treatment with clams for three months reduced Fas/L and Caspase-3 in the Meretrix lusoria and Geloina eros groups, but Fas-associated death domain (FADD) and Caspase-8 were strongly reduced in the Geloina eros group. For the mitochondria-dependent apoptotic pathway, the reduction of apoptosis proteins were observed in the hearts of clams-treated AD mice. BAK and Caspase-9 was reduced in the Meretrix lusoria group, but Caspase-3 and Cytochrome-c were reduced in Geloina eros group. Enhancement of survival proteins p-AKT, p-IGF1R, p-PI3K, Bcl-XL, Bcl2, and the longevity SIRT1 signaling proteins, p-AMPK-α, SIRT1, PGC1-α, p-FOXO3 were observed in clams-treated mice and even more strongly enhanced in the Meretrix lusoria, Geloina eros and Corbicula fluminea groups. This study observed that the ingestion of clams caused a reduction of apoptosis proteins and enhancement of survival and SIRT1 signaling proteins in the hearts. Full article

(This article belongs to the Special Issue Marine Compounds in Neurodegenerative Diseases)

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11 pages, 1905 KiB

Open AccessArticle

A Novel Peptide, Nicotinyl–Isoleucine–Valine–Histidine (NA–IVH), Promotes Antioxidant Gene Expression and Wound Healing in HaCaT Cells

by Dong Hwee Son, Dong Joo Yang, Ji Su Sun, Seul Ki Kim, Namju Kang, Jung Yun Kang, Yun-Hee Choi, Jeong Hun Lee, Sang Hyun Moh, Dong Min Shin and Ki Woo Kim

Mar. Drugs 2018, 16(8), 262; https://doi.org/10.3390/md16080262 - 1 Aug 2018

Cited by 16 | Viewed by 4671

Abstract

Nicotinamide (NA), a water-soluble vitamin B₃, has been shown to exert cellular-protective effects against reactive oxygen species (ROS). In order to improve the cellular-protective effects of NA, we synthesized a novel compound, nicotinyl–isoleucine–valine–histidine (NA–IVH), by combining NA with jellyfish peptides’ IVH. [...] Read more.

Nicotinamide (NA), a water-soluble vitamin B₃, has been shown to exert cellular-protective effects against reactive oxygen species (ROS). In order to improve the cellular-protective effects of NA, we synthesized a novel compound, nicotinyl–isoleucine–valine–histidine (NA–IVH), by combining NA with jellyfish peptides’ IVH. In the present study, we examined the cellular-protective effects of the novel synthetic nicotinyl-peptide, NA–IVH. We found that NA–IVH enhances the radical scavenging activity with a robust increase of the nuclear factor (erythroid-derived 2)-like factor (Nrf2) expression in human HaCaT keratinocytes. In addition, NA–IVH protected the cells from hydrogen peroxide (H₂O₂)-induced cell death. Interestingly, NA–IVH exhibited an improved wound-healing effect in a high glucose condition, possibly through the regulation of reactive oxygen species (ROS). Collectively, our results imply that a novel nicotinyl-peptide, NA–IVH, has a wound-healing effect in a hyperglycemic condition, possibly by modulating excessive ROS. Full article

(This article belongs to the Special Issue The Pharmacological Potential of Marine-Derived Peptides and Proteins)

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18 pages, 2987 KiB

Open AccessArticle

Antitumor Activity of Quinazolinone Alkaloids Inspired by Marine Natural Products

by Solida Long, Diana I. S. P. Resende, Anake Kijjoa, Artur M. S. Silva, André Pina, Tamara Fernández-Marcelo, M. Helena Vasconcelos, Emília Sousa and Madalena M. M. Pinto

Mar. Drugs 2018, 16(8), 261; https://doi.org/10.3390/md16080261 - 31 Jul 2018

Cited by 37 | Viewed by 6577

Abstract

Many fungal quinazolinone metabolites, which contain the methyl-indole pyrazino [1,2-b]quinazoline-3,6-dione core, have been found to possess promising antitumor activity. The purpose of this work was to synthesize the enantiomeric pairs of two members of this quinazolinone family, to explore their potential [...] Read more.

Many fungal quinazolinone metabolites, which contain the methyl-indole pyrazino [1,2-b]quinazoline-3,6-dione core, have been found to possess promising antitumor activity. The purpose of this work was to synthesize the enantiomeric pairs of two members of this quinazolinone family, to explore their potential as antitumor and their ability to revert multidrug resistance. The marine natural product fiscalin B (4c), and antienantiomers (4b, 5b, and 5c) were synthesized via a one-pot approach, while the syn enantiomers (4a, 4d, 5a, and 5d) were synthetized by a multi-step procedure. These strategies used anthranilic acid (i), chiral N-protected α-amino acids (ii), and tryptophan methyl esters (iii) to form the core ring of pyrazino[2,1-b]quinazoline-3,6-dione scaffold. Four enantiomeric pairs, with different enantiomeric purities, were obtained with overall yields ranging from 7 to 40%. Compounds 4a–d and 5a–d were evaluated for their growth inhibitory effect against two tumor cell lines. Differences between enantiomeric pairs were noted and 5a–d displayed GI₅₀ values ranging from 31 to 52 μM, which are lower than those of 4a–d. Nevertheless, no effect on P-glycoprotein (P-gp) modulation was observed for all compounds. This study disclosed new data for fiscalin B (4c), as well as for its analogues for a future development of novel anticancer drug leads. Full article

(This article belongs to the Special Issue Synthesis of Marine-Derived Compounds)

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