Marine Drugs

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Open AccessArticle

Growth, Toxin Production and Allelopathic Effects of Pseudo-nitzschia multiseries under Iron-Enriched Conditions

by Bruna Fernanda Sobrinho, Luana Mocelin De Camargo, Leonardo Sandrini-Neto, Cristian Rafael Kleemann, Eunice da Costa Machado and Luiz Laureno Mafra

Mar. Drugs 2017, 15(10), 331; https://doi.org/10.3390/md15100331 - 24 Oct 2017

Cited by 17 | Viewed by 5107

Abstract

In order to assess the effects of Fe-enrichment on the growth and domoic acid (DA) production of the toxigenic diatom Pseudo-nitzschia multiseries, static cultures that received the addition of different iron (Fe) concentrations were maintained for 30 days. Intra- and extracellular DA [...] Read more.

In order to assess the effects of Fe-enrichment on the growth and domoic acid (DA) production of the toxigenic diatom Pseudo-nitzschia multiseries, static cultures that received the addition of different iron (Fe) concentrations were maintained for 30 days. Intra- and extracellular DA concentrations were evaluated over time, and growth and chain-formation were compared to those of non-toxic diatoms, Bacillaria sp. Growth rates of P. multiseries (μ = 0.45–0.73 d⁻¹) were similar among cultures containing different Fe concentrations. Likewise, the similar incidence and length of P. multiseries stepped cell chains (usually 2–4; up to 8-cell long) among the treatments reinforces that the cultures were not growth-inhibited under any condition tested, suggesting an efficient Fe acquisition mechanism. Moreover, DA concentrations were significantly higher under the highest Fe concentration, indicating that Fe is required for toxin synthesis. Bacillaria sp. reached comparable growth rates under the same Fe concentrations, except when the dissolved cell contents from a P. multiseries culture was added. The 50–70% reduction in cell density and 70–90% decrease in total chlorophyll-a content of Bacillaria sp. at early stationary growth phase indicates, for the first time, an allelopathic effect of undetermined compounds released by Pseudo-nitzschia to another diatom species. Full article

(This article belongs to the Special Issue Harmful Marine Phytoplankton)

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Open AccessArticle

Accumulation and Tissue Distribution of Dinophysitoxin-1 and Dinophysitoxin-3 in the Mussel Crenomytilus grayanus Feeding on the Benthic Dinoflagellate Prorocentrum foraminosum

by Polina A. Kameneva, Ekaterina A. Krasheninina, Valentina V. Slobodskova, Sergey P. Kukla and Tatiana Yu. Orlova

Mar. Drugs 2017, 15(10), 330; https://doi.org/10.3390/md15100330 - 24 Oct 2017

Cited by 10 | Viewed by 3529

Abstract

A DTX-1-producing microalga, Prorocentrum foraminosum, from Peter the Great Bay, Sea of Japan, was fed to Gray’s mussels, Crenomytilus grayanus, for 12 days. An increase in DTX-1 and 7-O-acyl-DTX-1 (DTX-3) was observed in the digestive gland, kidneys, and gills. [...] Read more.

A DTX-1-producing microalga, Prorocentrum foraminosum, from Peter the Great Bay, Sea of Japan, was fed to Gray’s mussels, Crenomytilus grayanus, for 12 days. An increase in DTX-1 and 7-O-acyl-DTX-1 (DTX-3) was observed in the digestive gland, kidneys, and gills. The digestive gland accumulated 91–100% of DTX-1 + DTX-3; and kidneys and gills accumulated, up to 8.5% and 4.3%, respectively. The kidneys had a distinctive pattern of toxin accumulation where the concentration of DTX-1 did not grow significantly after the eighth day of feeding, indicating the potential of DTX-1 elimination. The digestive gland and gills predominantly accumulated DTX-1, with a dramatic increase between Days 8 and 12. The DTX-3 content was highest in the digestive gland. The composition of DTX-3 in the acyl groups was similar for the digestive gland and kidneys, and did not change during feeding. The total toxin uptake of mussels exceeded the total toxin content from ingested cells by 2.4 times, showing that toxins may have accumulated from the seawater. This assumption needs to be further proved. The muscle, gonads, and mantle remained free of toxins. No genotoxic effect was observed in the gills and digestive gland. Full article

(This article belongs to the Special Issue Algal Toxins II, 2017)

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Open AccessFeature PaperReview

Marine-Derived Penicillium Species as Producers of Cytotoxic Metabolites

by Sen Liu, Mingzhi Su, Shao-Jiang Song and Jee H. Jung

Mar. Drugs 2017, 15(10), 329; https://doi.org/10.3390/md15100329 - 24 Oct 2017

Cited by 65 | Viewed by 5717

Abstract

Since the discovery of penicillin, Penicillium has become one of the most attractive fungal genera for the production of bioactive molecules. Marine-derived Penicillium has provided numerous excellent pharmaceutical leads over the past decades. In this review, we focused on the cytotoxic metabolites * [...] Read more.

Since the discovery of penicillin, Penicillium has become one of the most attractive fungal genera for the production of bioactive molecules. Marine-derived Penicillium has provided numerous excellent pharmaceutical leads over the past decades. In this review, we focused on the cytotoxic metabolites * (* Cytotoxic potency was referred to five different levels in this review, extraordinary (IC₅₀/LD₅₀: <1 μM or 0.5 μg/mL); significant (IC₅₀/LD₅₀: 1~10 μM or 0.5~5 μg/mL); moderate (IC₅₀/LD₅₀: 10~30 μM or 5~15 μg/mL); mild (IC₅₀/LD₅₀: 30~50 μM or 15~25 μg/mL); weak (IC₅₀/LD₅₀: 50~100 μM or 25~50 μg/mL). The comparative potencies of positive controls were referred when they were available). produced by marine-derived Penicillium species, and on their cytotoxicity mechanisms, biosyntheses, and chemical syntheses. Full article

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Open AccessArticle

Release Behavior and Antibacterial Activity of Chitosan/Alginate Blends with Aloe vera and Silver Nanoparticles

by Luisa Fernanda Gómez Chabala, Claudia Elena Echeverri Cuartas and Martha Elena Londoño López

Mar. Drugs 2017, 15(10), 328; https://doi.org/10.3390/md15100328 - 24 Oct 2017

Cited by 85 | Viewed by 8182

Abstract

Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic purposes that is rich in amino acids, enzymes, vitamins and polysaccharides, which are responsible for its therapeutic properties. Incorporating these properties into a biopolymer film obtained from alginate and chitosan allowed [...] Read more.

Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic purposes that is rich in amino acids, enzymes, vitamins and polysaccharides, which are responsible for its therapeutic properties. Incorporating these properties into a biopolymer film obtained from alginate and chitosan allowed the development of a novel wound dressing with antibacterial capacity and healing effects to integrate the antibacterial capacity of silver nanoparticles with the healing and emollient properties of Aloe vera gel. Three alginate-chitosan matrices were obtained through blending methods using different proportions of alginate, chitosan, the Aloe vera (AV) gel and silver nanoparticles (AgNps), which were incorporated into the polymeric system through immersion methods. Physical, chemical and antibacterial characteristics were evaluated in each matrix. Interaction between alginate and chitosan was identified using the Fourier transform infrared spectroscopy technique (FTIR), porosity was studied using scanning electron microscopy (SEM), swelling degree was calculated by difference in weight, Aloe vera gel release capacity was estimated by applying a drug model (Peppas) and finally antibacterial capacity was evaluated against S. Aureus and P. aeruginosa. Results show that alginate-chitosan (A (1:3 Chit 1/Alg 1); B (1:3 Chit 1.5/Alg 1) and C (3:1 Chit 1/Alg 1/B12)) matrices with Aloe vera (AV) gel and silver nanoparticles (AgNps) described here displayed antibacterial properties and absorption and Aloe vera release capacity making it a potential wound dressing for minor injuries. Full article

(This article belongs to the Special Issue Marine Oligosaccharides and Polysaccharides)

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Open AccessReview

Recent Advances in the Isolation, Synthesis and Biological Activity of Marine Guanidine Alkaloids

by Jin Liu, Xu-Wen Li and Yue-Wei Guo

Mar. Drugs 2017, 15(10), 324; https://doi.org/10.3390/md15100324 - 24 Oct 2017

Cited by 27 | Viewed by 7888

Abstract

Marine organisms are prolific resources of guanidine-containing natural products with intriguing structures and promising biological activities. These molecules have therefore attracted the attention of chemists and biologists for their further studies towards potential drug leads. This review focused on the guanidine alkaloids derived [...] Read more.

Marine organisms are prolific resources of guanidine-containing natural products with intriguing structures and promising biological activities. These molecules have therefore attracted the attention of chemists and biologists for their further studies towards potential drug leads. This review focused on the guanidine alkaloids derived from marine sources and discussed the recent progress on their isolation, synthesis and biological activities, covering the literature from the year 2010 to the present. Full article

(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))

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Open AccessArticle

Anti-Inflammatory Cembranoids from the Soft Coral Lobophytum crassum

by Kuei-Hung Lai, Wan-Jing You, Chi-Chen Lin, Mohamed El-Shazly, Zuo-Jian Liao and Jui-Hsin Su

Mar. Drugs 2017, 15(10), 327; https://doi.org/10.3390/md15100327 - 23 Oct 2017

Cited by 44 | Viewed by 6145

Abstract

Abstract: Cembrane-type diterpenoids are among the most frequently encountered natural products from the soft corals of the genus Lobophytum. In the course of our investigation to identify anti-inflammatory constituents from a wild-type soft coral Lobophytum crassum, two new cembranoids, lobophyolide [...] Read more.

Abstract: Cembrane-type diterpenoids are among the most frequently encountered natural products from the soft corals of the genus Lobophytum. In the course of our investigation to identify anti-inflammatory constituents from a wild-type soft coral Lobophytum crassum, two new cembranoids, lobophyolide A (1) and B (2), along with five known compounds (3–7), were isolated. The structures of these natural products were identified using NMR and MS spectroscopic analyses. Compound 1 was found to possess the first identified α-epoxylactone group among all cembrane-type diterpenoids. The in vitro anti-inflammatory effect of compounds 1–5 was evaluated. The results showed that compounds 1–5 not only reduced IL-12 release, but also attenuated NO production in LPS-activated dendritic cells. Our data indicated that the isolated series of cembrane-type diterpenoids demonstrated interesting structural features and anti-inflammatory activity which could be further developed into therapeutic entities. Full article

(This article belongs to the Special Issue In Vitro and In Vivo Approaches in the Driving Seat of Marine Drugs Discovery)

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Open AccessReview

Mycosporine-Like Amino Acids: Potential Health and Beauty Ingredients

by Ewelina Chrapusta, Ariel Kaminski, Kornelia Duchnik, Beata Bober, Michal Adamski and Jan Bialczyk

Mar. Drugs 2017, 15(10), 326; https://doi.org/10.3390/md15100326 - 21 Oct 2017

Cited by 141 | Viewed by 13374

Abstract

Human skin is constantly exposed to damaging ultraviolet radiation (UVR), which induces a number of acute and chronic disorders. To reduce the risk of UV-induced skin injury, people apply an additional external protection in the form of cosmetic products containing sunscreens. Nowadays, because [...] Read more.

Human skin is constantly exposed to damaging ultraviolet radiation (UVR), which induces a number of acute and chronic disorders. To reduce the risk of UV-induced skin injury, people apply an additional external protection in the form of cosmetic products containing sunscreens. Nowadays, because of the use of some chemical filters raises a lot of controversies, research focuses on exploring novel, fully safe and highly efficient natural UV-absorbing compounds that could be used as active ingredients in sun care products. A promising alternative is the application of multifunctional mycosporine-like amino acids (MAAs), which can effectively compete with commercially available filters. Here, we outline a complete characterization of these compounds and discuss their enormous biotechnological potential with special emphasis on their use as sunscreens, activators of cells proliferation, anti-cancer agents, anti-photoaging molecules, stimulators of skin renewal, and functional ingredients of UV-protective biomaterials. Full article

(This article belongs to the Special Issue Marine Products for Health and Beauty)

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Open AccessReview

Pleiotropic Role of Puupehenones in Biomedical Research

by Beatriz Martínez-Poveda, Ana R. Quesada and Miguel Ángel Medina

Mar. Drugs 2017, 15(10), 325; https://doi.org/10.3390/md15100325 - 21 Oct 2017

Cited by 15 | Viewed by 4498

Abstract

Marine sponges represent a vast source of metabolites with very interesting potential biomedical applications. Puupehenones are sesquiterpene quinones isolated from sponges of the orders Verongida and Dictyoceratida. This family of chemical compounds is composed of a high number of metabolites, including puupehenone, the [...] Read more.

Marine sponges represent a vast source of metabolites with very interesting potential biomedical applications. Puupehenones are sesquiterpene quinones isolated from sponges of the orders Verongida and Dictyoceratida. This family of chemical compounds is composed of a high number of metabolites, including puupehenone, the most characteristic compound of the family. Chemical synthesis of puupehenone has been reached by different routes, and the special chemical reactivity of this molecule has allowed the synthesis of many puupehenone-derived compounds. The biological activities of puupehenones are very diverse, including antiangiogenic, antitumoral, antioxidant, antimicrobial, immunomodulatory and antiatherosclerotic effects. Despite the very important roles described for puupehenones concerning different pathologies, the exact mechanism of action of these compounds and the putative therapeutic effects in vivo remain to be elucidated. This review offers an updated and global view about the biology of puupehenones and their therapeutic possibilities in human diseases such as cancer. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Different Levels of Skin Whitening Activity among 3,6-Anhydro-l-galactose, Agarooligosaccharides, and Neoagarooligosaccharides

by Ji Hye Kim, Eun Ju Yun, Sora Yu, Kyoung Heon Kim and Nam Joo Kang

Mar. Drugs 2017, 15(10), 321; https://doi.org/10.3390/md15100321 - 20 Oct 2017

Cited by 71 | Viewed by 7020

Abstract

3,6-Anhydro-l-galactose (AHG), a major monomeric constituent of red macroalgae (Rhodophyta), was recently reported to possess skin whitening activity. Moreover, AHG-containing oligosaccharides, such as agarooligosaccharides (AOSs) and neoagarooligosaccharides (NAOSs), have various physiological activities, including anti-inflammatory, antioxidant, and skin moisturizing effects. [...] Read more.

3,6-Anhydro-l-galactose (AHG), a major monomeric constituent of red macroalgae (Rhodophyta), was recently reported to possess skin whitening activity. Moreover, AHG-containing oligosaccharides, such as agarooligosaccharides (AOSs) and neoagarooligosaccharides (NAOSs), have various physiological activities, including anti-inflammatory, antioxidant, and skin moisturizing effects. In this study, AHG and NAOSs were produced from agarose by enzymatic reactions catalyzed by an endo-type β-agarase, an exo-type β-agarase, and a neoagarobiose hydrolase. In a cell proliferation assay, AHG, AOSs, and NAOSs at 12.5, 25, and 50 μg/mL concentrations did not exhibit cytotoxicity toward murine B16 melanoma cells or human epidermal melanocytes. In an in vitro skin whitening activity assay of AHG, AOSs, and NAOSs at 50 μg/mL, AHG showed the highest skin whitening activity in both murine B16 melanoma cells and human epidermal melanocytes; this activity was mediated by the inhibition of melanogenesis. Neoagarotetraose and neoagarohexaose also exhibited in vitro skin whitening activity, whereas neoagarobiose and AOSs with degrees of polymerization of 3 (agarotriose), 5 (agaropentaose), and 7 (agaroheptaose) did not. Therefore, AHG is responsible for the skin whitening activity of agar-derived sugars, and the structural differences among the AHG-containing oligosaccharides may be responsible for their different skin whitening activities. Full article

(This article belongs to the Special Issue Marine Products for Health and Beauty)

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Open AccessFeature PaperArticle

A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti-Austerity Agent against Starved Tumor Cells

by Haruhiko Fuwa and Mizuho Sato

Mar. Drugs 2017, 15(10), 320; https://doi.org/10.3390/md15100320 - 20 Oct 2017

Cited by 13 | Viewed by 4366

Abstract

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human [...] Read more.

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells. Full article

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Open AccessArticle

Chitosan Ascorbate Nanoparticles for the Vaginal Delivery of Antibiotic Drugs in Atrophic Vaginitis

by Silvia Rossi, Barbara Vigani, Antonella Puccio, Maria Cristina Bonferoni, Giuseppina Sandri and Franca Ferrari

Mar. Drugs 2017, 15(10), 319; https://doi.org/10.3390/md15100319 - 19 Oct 2017

Cited by 36 | Viewed by 4451

Abstract

The aim of the present work was the development of chitosan ascorbate nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with amoxicillin trihydrate (AX) were obtained by ionotropic [...] Read more.

The aim of the present work was the development of chitosan ascorbate nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with amoxicillin trihydrate (AX) were obtained by ionotropic gelation in the presence of pentasodium tripolyphosphate (TPP). Different CSA:TPP and CSA:AX weight ratios were considered and their influence on the particle size, polydispersion index and production yield were investigated. CSA NPs were characterized for mucoadhesive, wound healing and antimicrobial properties. Subsequently, CSA NPs were loaded in polymeric matrices, whose composition was optimized using a DoE (Design of Experiments) approach (simplex centroid design). Matrices were obtained by freeze-drying aqueous solutions of three hydrophilic excipients, polyvinylpirrolidone, mannitol and glycin. They should possess a mechanical resistance suitable for the administration into the vaginal cavity and should readily dissolve in the vaginal fluid. In addition to antioxidant properties, due to the presence of ascorbic acid, CSA NPs showed in vitro mucoadhesive, wound healing and antimicrobial properties. In particular, nanoparticles were characterized by an improved antimicrobial activity with respect to a chitosan solution, prepared at the same concentration. The optimized matrix was characterized by mechanical resistance and by the fast release in simulated vaginal fluid of nanoparticles characterized by unchanged size. Full article

(This article belongs to the Special Issue Marine Biomaterials II, 2017)

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Open AccessArticle

Identification and Characterization of an Isoform Antifreeze Protein from the Antarctic Marine Diatom, Chaetoceros neogracile and Suggestion of the Core Region

by Minjae Kim, Yunho Gwak, Woongsic Jung and EonSeon Jin

Mar. Drugs 2017, 15(10), 318; https://doi.org/10.3390/md15100318 - 18 Oct 2017

Cited by 10 | Viewed by 5292

Abstract

Antifreeze proteins (AFPs) protecting the cells against freezing are produced in response to extremely low temperatures in diverse psychrophilic organisms, and they are encoded by multiple gene families. The AFP of Antarctic marine diatom Chaetoceros neogracile is reported in our previous research, but [...] Read more.

Antifreeze proteins (AFPs) protecting the cells against freezing are produced in response to extremely low temperatures in diverse psychrophilic organisms, and they are encoded by multiple gene families. The AFP of Antarctic marine diatom Chaetoceros neogracile is reported in our previous research, but like other microalgae, was considered to probably have additional genes coding AFPs. In this paper, we reported the cloning and characterization of additional AFP gene from C. neogracile (Cn-isoAFP). Cn-isoAFP protein is 74.6% identical to the previously reported Cn-AFP. The promoter sequence of Cn-isoAFP contains environmental stress responsive elements for cold, thermal, and high light conditions. Cn-isoAFP transcription levels increased dramatically when cells were exposed to freezing (−20 °C), thermal (10 °C), or high light (600 μmol photon m⁻² s⁻¹) stresses. The thermal hysteresis (TH) activity of recombinant Cn-isoAFP was 0.8 °C at a protein concentration of 5 mg/mL. Results from homology modeling and TH activity analysis of site-directed mutant proteins elucidated AFP mechanism to be a result of flatness of B-face maintained via hydrophobic interactions. Full article

(This article belongs to the Special Issue Marine Ice-binding Proteins and Their Mimetics: Structure, Function, and Application)

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Open AccessReview

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

by Muhammad Abdul Mojid Mondol, Hee Jae Shin, M. Aminur Rahman and Mohamad Tofazzal Islam

Mar. Drugs 2017, 15(10), 317; https://doi.org/10.3390/md15100317 - 17 Oct 2017

Cited by 64 | Viewed by 9397

Abstract

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified [...] Read more.

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural–activity relationships (SARs) of sea cucumber glycosides are also discussed briefly. Full article

(This article belongs to the Special Issue Marine Glycosides)

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Open AccessArticle

Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases

by Nadège Loaëc, Eletta Attanasio, Benoît Villiers, Emilie Durieu, Tania Tahtouh, Morgane Cam, Rohan A. Davis, Aline Alencar, Mélanie Roué, Marie-Lise Bourguet-Kondracki, Peter Proksch, Emmanuelle Limanton, Solène Guiheneuf, François Carreaux, Jean-Pierre Bazureau, Michelle Klautau and Laurent Meijer

Mar. Drugs 2017, 15(10), 316; https://doi.org/10.3390/md15100316 - 17 Oct 2017

Cited by 42 | Viewed by 5968

Abstract

A large diversity of 2-aminoimidazolone alkaloids is produced by various marine invertebrates, especially by the marine Calcareous sponges Leucetta and Clathrina. The phylogeny of these sponges and the wide scope of 2-aminoimidazolone alkaloids they produce are reviewed in this article. The origin [...] Read more.

A large diversity of 2-aminoimidazolone alkaloids is produced by various marine invertebrates, especially by the marine Calcareous sponges Leucetta and Clathrina. The phylogeny of these sponges and the wide scope of 2-aminoimidazolone alkaloids they produce are reviewed in this article. The origin (invertebrate cells, associated microorganisms, or filtered plankton), physiological functions, and natural molecular targets of these alkaloids are largely unknown. Following the identification of leucettamine B as an inhibitor of selected protein kinases, we synthesized a family of analogues, collectively named leucettines, as potent inhibitors of DYRKs (dual-specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases) and potential pharmacological leads for the treatment of several diseases, including Alzheimer’s disease and Down syndrome. We assembled a small library of marine sponge- and ascidian-derived 2-aminoimidazolone alkaloids, along with several synthetic analogues, and tested them on a panel of mammalian and protozoan kinases. Polyandrocarpamines A and B were found to be potent and selective inhibitors of DYRKs and CLKs. They inhibited cyclin D1 phosphorylation on a DYRK1A phosphosite in cultured cells. 2-Aminoimidazolones thus represent a promising chemical scaffold for the design of potential therapeutic drug candidates acting as specific inhibitors of disease-relevant kinases, and possibly other disease-relevant targets. Full article

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

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Open AccessFeature PaperArticle

Algal Foams Applied in Fixed-Bed Process for Lead(II) Removal Using Recirculation or One-Pass Modes

by Shengye Wang, Thierry Vincent, Catherine Faur and Eric Guibal

Mar. Drugs 2017, 15(10), 315; https://doi.org/10.3390/md15100315 - 17 Oct 2017

Cited by 11 | Viewed by 3950

Abstract

The incorporation of brown algae into biopolymer beads or foams for metal sorption has been previously reported. However, the direct use of these biomasses for preparing foams is a new approach. In this study, two kinds of porous foams were prepared by ionotropic [...] Read more.

The incorporation of brown algae into biopolymer beads or foams for metal sorption has been previously reported. However, the direct use of these biomasses for preparing foams is a new approach. In this study, two kinds of porous foams were prepared by ionotropic gelation using algal biomass (AB, Laminaria digitata) or alginate (as the reference) and applied for Pb(II) sorption. These foams (manufactured as macroporous discs) were packed in filtration holders (simulating fixed-bed column) and the system was operated in either a recirculation or a one-pass mode. Sorption isotherms, uptake kinetics and sorbent reuse were studied in the recirculation mode (analogous to batch system). In the one-pass mode (continuous fixed-bed system), the influence of parameters such as flow rate, feed metal concentration and bed height were investigated on both sorption and desorption. In addition, the effect of Cu(II) on Pb(II) recovery from binary solutions was also studied in terms of both sorption and desorption. Sorption isotherms are well fitted by the Langmuir equation while the pseudo-second order rate equation described well both sorption and desorption kinetic profiles. The study of material regeneration confirms that the reuse of the foams was feasible with a small mass loss, even after 9 cycles. In the one-pass mode, for alginate foams, a slower flow rate led to a smaller saturation volume, while the effect of flow rate was less marked for AB foams. Competitive study suggests that the foams have a preference for Pb(II) over Cu(II) but cannot selectively remove Pb(II) from the binary solution. Full article

(This article belongs to the Special Issue Marine Compounds Used in Biosorption)

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Open AccessArticle

Identification of (Z)-2,3-Diphenylacrylonitrile as Anti-Cancer Molecule in Persian Gulf Sea Cucumber Holothuria parva

by Salimeh Amidi, Zahra Hashemi, Abbasali Motallebi, Melika Nazemi, Hoda Farrokhpayam, Enayatollah Seydi and Jalal Pourahmad

Mar. Drugs 2017, 15(10), 314; https://doi.org/10.3390/md15100314 - 16 Oct 2017

Cited by 11 | Viewed by 5272

Abstract

Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions for the possible existence of selective toxicity [...] Read more.

Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions for the possible existence of selective toxicity on liver mitochondria isolated from an animal model of HCC. Next, we purified the most active fraction. Thus the structure of the active molecule was identified. HCC was induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol. Rat liver mitochondria for evaluation of the selective cytotoxic effects of sub-fractions of H. parva were isolated and then mitochondrial parameters were determined. Our results showed that C1 sub-fraction of methanolic extract of H. parva considerably increased reactive oxygen species (ROS) generation, collapse of mitochondrial membrane potential (MMP), swelling in mitochondria and cytochrome c release only on HCC liver mitochondria. Furthermore, the methanolic extract of H. parva was investigated furthermore and the active fraction was extracted. In this fraction, (Z)-2,3-diphenylacrylonitrile molecule, which is also known as α-cyanostilbene, was identified by mass analysis. This molecule increased ROS generation, collapse of MMP, swelling in mitochondria and finally cytochrome c release only on HCC liver mitochondria. The derivatives of (Z)-2,3-diphenylacrylonitrile in other natural products were also reported as an anti-cancer agent. These results suggest the eligibility of the (Z)-2,3-diphenylacrylonitrile as a complementary therapeutic agent for patients with HCC. Full article

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Open AccessFeature PaperReview

Conotoxins as Tools to Understand the Physiological Function of Voltage-Gated Calcium (Ca_V) Channels

by David Ramírez, Wendy Gonzalez, Rafael A. Fissore and Ingrid Carvacho

Mar. Drugs 2017, 15(10), 313; https://doi.org/10.3390/md15100313 - 13 Oct 2017

Cited by 34 | Viewed by 5643

Abstract

Voltage-gated calcium (Ca_V) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human [...] Read more.

Voltage-gated calcium (Ca_V) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. Ca_V channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, Ca_V1.1–1.4; Ca_V2.1–2.3) and Low-voltage activated (LVA, Ca_V3.1–3.3). HVA channels are highly expressed in brain (neurons), heart, and adrenal medulla (chromaffin cells), among others, and are also classified into subtypes which can be distinguished using pharmacological approaches. Cone snails are marine gastropods that capture their prey by injecting venom, “conopeptides”, which cause paralysis in a few seconds. A subset of conopeptides called conotoxins are relatively small polypeptides, rich in disulfide bonds, that target ion channels, transporters and receptors localized at the neuromuscular system of the animal target. In this review, we describe the structure and properties of conotoxins that selectively block HVA calcium channels. We compare their potency on several HVA channel subtypes, emphasizing neuronal calcium channels. Lastly, we analyze recent advances in the therapeutic use of conotoxins for medical treatments. Full article

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

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Open AccessArticle

Discovering the Biological Target of 5-epi-Sinuleptolide Using a Combination of Proteomic Approaches

by Elva Morretta, Roberta Esposito, Carmen Festa, Raffaele Riccio, Agostino Casapullo and Maria Chiara Monti

Mar. Drugs 2017, 15(10), 312; https://doi.org/10.3390/md15100312 - 13 Oct 2017

Cited by 21 | Viewed by 5478

Abstract

Sinuleptolide and its congeners are diterpenes with a norcembranoid skeleton isolated from the soft coral genus Sinularia. These marine metabolites are endowed with relevant biological activities, mainly associated with cancer development. 5-epi-sinuleptolide has been selected as a candidate for target [...] Read more.

Sinuleptolide and its congeners are diterpenes with a norcembranoid skeleton isolated from the soft coral genus Sinularia. These marine metabolites are endowed with relevant biological activities, mainly associated with cancer development. 5-epi-sinuleptolide has been selected as a candidate for target discovery studies through the application of complementary proteomic approaches. Specifically, a combination of conventional chemical proteomics based on affinity chromatography, coupled with high-resolution mass spectrometry and bioinformatics, as well as drug affinity responsive target stability (DARTS), led to a clear identification of actins as main targets for 5-epi-sinuleptolide. Subsequent in-cell assays, performed with cytochalasin D as reference compound, gave information on the ability of 5-epi-sinuleptolide to disrupt the actin cytoskeleton by loss of actin fibers and formation of F-actin amorphous aggregates. These results suggest the potential application of 5-epi-sinuleptolide as a useful tool in the study of the molecular processes impaired in several disorders in which actin is thought to play an essential role. Full article

(This article belongs to the Special Issue Target Identification of Marine Products)

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Open AccessArticle

Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity, Antioxidant Properties, Phenolic Content and Amino Acid Profiles of Fucus spiralis L. Protein Hydrolysate Fractions

by Lisete Paiva, Elisabete Lima, Ana Isabel Neto and José Baptista

Mar. Drugs 2017, 15(10), 311; https://doi.org/10.3390/md15100311 - 13 Oct 2017

Cited by 77 | Viewed by 5499

Abstract

Food protein-derived hydrolysates with multi-bioactivities such as antihypertensive and antioxidant properties have recently received special attention since both activities can play significant roles in preventing cardiovascular diseases. This study reports, for the first time, the angiotensin I-converting enzyme (ACE)-inhibition and antioxidant properties of [...] Read more.

Food protein-derived hydrolysates with multi-bioactivities such as antihypertensive and antioxidant properties have recently received special attention since both activities can play significant roles in preventing cardiovascular diseases. This study reports, for the first time, the angiotensin I-converting enzyme (ACE)-inhibition and antioxidant properties of ultrafiltrate fractions (UF) with different molecular weight ranges (<1, 1–3 and ≥3 kDa) obtained from Fucus spiralis protein hydrolysate (FSPH) digested with cellulase–bromelain. The amino acids profile, recovery yield, protein, peptide and total phenolic contents of these FSPH-UF, and the in vitro digestibility of F. spiralis crude protein were also investigated. FSPH-UF ≥3 kDa presented remarkably higher ACE-inhibition, yield, peptide and polyphenolic (phlorotannins) contents. Antioxidant analysis showed that FSPH-UF <1 kDa and ≥3 kDa exhibited significantly higher scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and ferrous ion-chelating (FIC) activity. FSPH-UF ≥3 kDa had also notably higher ferric reducing antioxidant power (FRAP). Strong correlations were observed between ACE-inhibition and antioxidant activities (FIC and FRAP). The results suggest that ACE-inhibition and antioxidant properties of FSPH-UF may be due to the bioactive peptides and polyphenols released during the enzymatic hydrolysis. In conclusion, this study shows the potential use of defined size FSPH-UF for the prevention/treatment of hypertension and/or oxidative stress-related diseases. Full article

(This article belongs to the Special Issue Development and Application of Herbal Medicine from Marine Origin)

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Open AccessFeature PaperReview

Marine Sponge Natural Products with Anticancer Potential: An Updated Review

by Cinzia Calcabrini, Elena Catanzaro, Anupam Bishayee, Eleonora Turrini and Carmela Fimognari

Mar. Drugs 2017, 15(10), 310; https://doi.org/10.3390/md15100310 - 13 Oct 2017

Cited by 117 | Viewed by 15120

Abstract

Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored [...] Read more.

Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy. Full article

(This article belongs to the Special Issue Marine Drugs as Antitumour Agents 2017)

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Open AccessReview

Guanidinium Toxins and Their Interactions with Voltage-Gated Sodium Ion Channels

by Lorena M. Durán-Riveroll and Allan D. Cembella

Mar. Drugs 2017, 15(10), 303; https://doi.org/10.3390/md15100303 - 13 Oct 2017

Cited by 60 | Viewed by 8970

Abstract

Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and [...] Read more.

Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and ion flux blockage capacity for voltage-gated sodium channels (Na_V). Members of the STX group, known collectively as paralytic shellfish toxins (PSTs), are produced among three genera of marine dinoflagellates and about a dozen genera of primarily freshwater or brackish water cyanobacteria. In contrast, toxins of the TTX group occur mainly in macrozoa, particularly among puffer fish, several species of marine invertebrates and a few terrestrial amphibians. In the case of TTX and analogs, most evidence suggests that symbiotic bacteria are the origin of the toxins, although endogenous biosynthesis independent from bacteria has not been excluded. The evolutionary origin of the biosynthetic genes for STX and analogs in dinoflagellates and cyanobacteria remains elusive. These highly potent molecules have been the subject of intensive research since the latter half of the past century; first to study the mode of action of their toxigenicity, and later as tools to characterize the role and structure of Na_V channels, and finally as therapeutics. Their pharmacological activities have provided encouragement for their use as therapeutants for ion channel-related pathologies, such as pain control. The functional role in aquatic and terrestrial ecosystems for both groups of toxins is unproven, although plausible mechanisms of ion channel regulation and chemical defense are often invoked. Molecular approaches and the development of improved detection methods will yield deeper understanding of their physiological and ecological roles. This knowledge will facilitate their further biotechnological exploitation and point the way towards development of pharmaceuticals and therapeutic applications. Full article

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

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Open AccessArticle

Quantification of Representative Ciguatoxins in the Pacific Using Quantitative Nuclear Magnetic Resonance Spectroscopy

by Tsuyoshi Kato and Takeshi Yasumoto

Mar. Drugs 2017, 15(10), 309; https://doi.org/10.3390/md15100309 - 12 Oct 2017

Cited by 24 | Viewed by 4371

Abstract

The absolute quantification of five toxins involved in ciguatera fish poisoning (CFP) in the Pacific was carried out by quantitative ¹H-NMR. The targeted toxins were ciguatoxin-1B (CTX1B), 52-epi-54-deoxyciguatoxin-1B (epideoxyCTX1B), ciguatoxin-3C (CTX3C), 51-hydroxyciguatoxin-3C (51OHCTX3C), and ciguatoxin-4A (CTX4A). We first calibrated the residual protons [...] Read more.

The absolute quantification of five toxins involved in ciguatera fish poisoning (CFP) in the Pacific was carried out by quantitative ¹H-NMR. The targeted toxins were ciguatoxin-1B (CTX1B), 52-epi-54-deoxyciguatoxin-1B (epideoxyCTX1B), ciguatoxin-3C (CTX3C), 51-hydroxyciguatoxin-3C (51OHCTX3C), and ciguatoxin-4A (CTX4A). We first calibrated the residual protons of pyridine-d₅ using certified reference material, 1,4-BTMSB-d₄, prepared the toxin solutions with the calibrated pyridin-d₅, measured the ¹H-NMR spectra, and quantified the toxin using the calibrated residual protons as the internal standard. The absolute quantification was carried out by comparing the signal intensities between the selected protons of the target toxin and the residual protons of the calibrated pyridine-d₅. The proton signals residing on the ciguatoxins (CTXs) to be used for quantification were carefully selected for those that were well separated from adjacent signals including impurities and that exhibited an effective intensity. To quantify CTX1B and its congeners, the olefin protons in the side chain were judged appropriate for use. The quantification was achievable with nano-molar solutions. The probable errors for uncertainty, calculated on respective toxins, ranged between 3% and 16%. The contamination of the precious toxins with nonvolatile internal standards was thus avoided. After the evaporation of pyridine-d₅, the calibrated CTXs were ready for use as the reference standard in the quantitative analysis of ciguatoxins by LC/MS. Full article

(This article belongs to the Special Issue Target Identification of Marine Products)

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Open AccessArticle

Diversity and Antimicrobial Potential of Predatory Bacteria from the Peruvian Coastline

by Luis Linares-Otoya, Virginia Linares-Otoya, Lizbeth Armas-Mantilla, Cyntia Blanco-Olano, Max Crüsemann, Mayar L. Ganoza-Yupanqui, Julio Campos-Florian, Gabriele M. König and Till F. Schäberle

Mar. Drugs 2017, 15(10), 308; https://doi.org/10.3390/md15100308 - 12 Oct 2017

Cited by 14 | Viewed by 5851

Abstract

The microbiome of three different sites at the Peruvian Pacific coast was analyzed, revealing a lower bacterial biodiversity at Isla Foca than at Paracas and Manglares, with 89 bacterial genera identified, as compared to 195 and 173 genera, respectively. Only 47 of the [...] Read more.

The microbiome of three different sites at the Peruvian Pacific coast was analyzed, revealing a lower bacterial biodiversity at Isla Foca than at Paracas and Manglares, with 89 bacterial genera identified, as compared to 195 and 173 genera, respectively. Only 47 of the bacterial genera identified were common to all three sites. In order to obtain promising strains for the putative production of novel antimicrobials, predatory bacteria were isolated from these sampling sites, using two different bait organisms. Even though the proportion of predatory bacteria was only around 0.5% in the here investigated environmental microbiomes, by this approach in total 138 bacterial strains were isolated as axenic culture. 25% of strains showed antibacterial activity, thereby nine revealed activity against clinically relevant methicillin resistant Staphylococcus aureus (MRSA) and three against enterohemorrhagic Escherichia coli (EHEC) strains. Phylogeny and physiological characteristics of the active strains were investigated. First insights into the chemical basis of the antibacterial activity indicated the biosynthetic production of the known compounds ariakemicin, kocurin, naphthyridinomycin, pumilacidins, resistomycin, and surfactin. However, most compounds remained elusive until now. Hence, the obtained results implicate that the microbiome present at the various habitats at the Peruvian coastline is a promising source for heterotrophic bacterial strains showing high potential for the biotechnological production of antibiotics. Full article

(This article belongs to the Special Issue Marine Antimicrobial Agents)

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Open AccessArticle

The Abundance of Toxic Genotypes Is a Key Contributor to Anatoxin Variability in Phormidium-Dominated Benthic Mats

by Susanna A. Wood and Jonathan Puddick

Mar. Drugs 2017, 15(10), 307; https://doi.org/10.3390/md15100307 - 11 Oct 2017

Cited by 25 | Viewed by 4329

Abstract

The prevalence of benthic proliferations of the anatoxin-producing cyanobacterium Phormidium are increasing in cobble-bed rivers worldwide. Studies to date have shown high spatial and temporal variability in anatoxin concentrations among mats. In this study we determined anatoxin quotas (toxins per cell) in field [...] Read more.

The prevalence of benthic proliferations of the anatoxin-producing cyanobacterium Phormidium are increasing in cobble-bed rivers worldwide. Studies to date have shown high spatial and temporal variability in anatoxin concentrations among mats. In this study we determined anatoxin quotas (toxins per cell) in field samples and compared these results to the conventionally-used concentrations (assessed per dry weight of mat). Three mats were selected at sites in two rivers and were sampled every 2–3 h for 24–26 h. The samples were lyophilized and ground to a fine homogenous powder. Two aliquots of known weights were analyzed for anatoxin congeners using liquid chromatography-mass spectrometry, or digital droplet PCR with Phormidium-specific anaC primers to measure absolute quantities of gene copies. Anatoxin concentrations in the mats varied 59- and 303-fold in the two rivers over the study periods. A similar pattern was observed among gene copies (53- and 2828-fold). When converted to anatoxin quotas there was markedly less variability (42- and 16-fold), but significantly higher anatoxin quotas were observed in mats from the second river (p < 0.001, Student’s t-test). There were no obvious temporal patterns with high and low anatoxin concentrations or quotas measured at each sampling time and across the study period. These results demonstrate that variability in anatoxin concentrations among mats is primarily due to the abundance of toxic genotypes. No consistent modulation in anatoxin production was observed during the study, although significant differences in anatoxin quotas among rivers suggest that site-specific physiochemical or biological factors may influence anatoxin production. Full article

(This article belongs to the Special Issue Algal Toxins II, 2017)

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Open AccessArticle

Sequencing and Characterization of Novel PII Signaling Protein Gene in Microalga Haematococcus pluvialis

by Ruijuan Ma, Yan Li and Yinghua Lu

Mar. Drugs 2017, 15(10), 304; https://doi.org/10.3390/md15100304 - 11 Oct 2017

Cited by 4 | Viewed by 5101

Abstract

The PII signaling protein is a key protein for controlling nitrogen assimilatory reactions in most organisms, but little information is reported on PII proteins of green microalga Haematococcus pluvialis. Since H. pluvialis cells can produce a large amount of astaxanthin upon nitrogen [...] Read more.

The PII signaling protein is a key protein for controlling nitrogen assimilatory reactions in most organisms, but little information is reported on PII proteins of green microalga Haematococcus pluvialis. Since H. pluvialis cells can produce a large amount of astaxanthin upon nitrogen starvation, its PII protein may represent an important factor on elevated production of Haematococcus astaxanthin. This study identified and isolated the coding gene (HpGLB1) from this microalga. The full-length of HpGLB1 was 1222 bp, including 621 bp coding sequence (CDS), 103 bp 5′ untranslated region (5′ UTR), and 498 bp 3′ untranslated region (3′ UTR). The CDS could encode a protein with 206 amino acids (HpPII). Its calculated molecular weight (Mw) was 22.4 kDa and the theoretical isoelectric point was 9.53. When H. pluvialis cells were exposed to nitrogen starvation, the HpGLB1 expression was increased 2.46 times in 48 h, concomitant with the raise of astaxanthin content. This study also used phylogenetic analysis to prove that HpPII was homogeneous to the PII proteins of other green microalgae. The results formed a fundamental basis for the future study on HpPII, for its potential physiological function in Haematococcus astaxanthin biosysthesis. Full article

(This article belongs to the Special Issue Marine Carotenoids)

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Open AccessArticle

Production of Fish Protein Hydrolysates from Scyliorhinus canicula Discards with Antihypertensive and Antioxidant Activities by Enzymatic Hydrolysis and Mathematical Optimization Using Response Surface Methodology

by José A. Vázquez, Maria Blanco, Agueda E. Massa, Isabel Rodríguez Amado and Ricardo I. Pérez-Martín

Mar. Drugs 2017, 15(10), 306; https://doi.org/10.3390/md15100306 - 10 Oct 2017

Cited by 53 | Viewed by 5485

Abstract

Fish discards are of major concern in new EU policies. Alternatives for the management of the new biomass that has to be landed is compulsory. The production of bioactive compounds from fish protein hydrolysates (FPH) has been explored in recent years. However, the [...] Read more.

Fish discards are of major concern in new EU policies. Alternatives for the management of the new biomass that has to be landed is compulsory. The production of bioactive compounds from fish protein hydrolysates (FPH) has been explored in recent years. However, the viability of Scyliorhinus canicula discards, which might account for up to 90–100% of captures in mixed trawler, gillnet, and longline industrial fisheries, to produce FPH from the muscle with bioactivities has still not been studied in terms of the optimization of the experimental conditions to enhance its production. The effect of pH and temperature on the hydrolysis of the S. canicula muscle was mediated by three commercial proteases using response surface methodology. Temperatures of 64.6 °C and 60.8 °C and pHs of 9.40 and 8.90 were established as the best hydrolysis conditions for Alcalase and Esperase, respectively. Optimization of the best conditions for the maximization of antihypertensive and antioxidant activities was performed. Higher Angiotensin-converting enzyme (ACE) activity was found with Esperase. The pH optimum and temperature optimum for antioxidants were 55 °C/pH8.0 for ABTS/DPPH-Esperase, 63.1 °C/pH9.0 for DPPH-Alcalase, and 55 °C/pH9.0 for ABTS-Alcalase. No hydrolysis was detected when using Protamex. Full article

(This article belongs to the Special Issue Bioconversion of Marine Resources)

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Open AccessArticle

Dual Biological Functions of a Cytoprotective Effect and Apoptosis Induction by Bioavailable Marine Carotenoid Fucoxanthinol through Modulation of the Nrf2 Activation in RAW264.7 Macrophage Cells

by Junsei Taira, Miki Sonamoto and Masatsugu Uehara

Mar. Drugs 2017, 15(10), 305; https://doi.org/10.3390/md15100305 - 6 Oct 2017

Cited by 15 | Viewed by 4729

Abstract

In this study, the function of fucoxanthinol (FxOH) as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx), was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1–4 μM) with a peroxyl radical scavenging [...] Read more.

In this study, the function of fucoxanthinol (FxOH) as a bioavailable marine carotenoid together with the pre-metabolite, fucoxanthin (Fx), was examined through the Nrf2-ARE pathway. The antioxidant activity in the low concentration range of the compounds (1–4 μM) with a peroxyl radical scavenging capacity was proved by the ORAC (Oxygen Radical Absorbance Capacity) method and an ESR study. Similar concentrations of the compound also activated the Nrf2-ARE signaling with the Nrf2 translocation into the nuclear, then the expression of the antioxidant protein HO-1 increased. On the other hand, the high concentrations of both compounds (>10 μM) induced apoptosis with caspase 3/7 activation during suppression of the anti-apoptotic proteins, such as Bcl-XL and phosphorous Akt (pAkt). The Nrf2 expression was then activated in the nuclear, indicating that the Nrf2 plays a significant role in the cytoprotective effect against the toxicity of the compounds. These results indicated that the compounds have the dual functions of a cytoprotective effect and the apoptosis induction dependent on the treated concentrations through the Nrf2 activation. In addition, the results of all the assays involved in our previous studies suggested that the metabolite FxOH having a higher activity than the Fx, will be a bioavailable compound in biological systems. Full article

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Open AccessArticle

Metabolite Profiling of Triterpene Glycosides of the Far Eastern Sea Cucumber Eupentacta fraudatrix and Their Distribution in Various Body Components Using LC-ESI QTOF-MS

by Roman S. Popov, Natalia V. Ivanchina, Alexandra S. Silchenko, Sergey A. Avilov, Vladimir I. Kalinin, Igor Yu. Dolmatov, Valentin A. Stonik and Pavel S. Dmitrenok

Mar. Drugs 2017, 15(10), 302; https://doi.org/10.3390/md15100302 - 2 Oct 2017

Cited by 20 | Viewed by 4829

Abstract

The Far Eastern sea cucumber Eupentacta fraudatrix is an inhabitant of shallow waters of the south part of the Sea of Japan. This animal is an interesting and rich source of triterpene glycosides with unique chemical structures and various biological activities. The objective [...] Read more.

The Far Eastern sea cucumber Eupentacta fraudatrix is an inhabitant of shallow waters of the south part of the Sea of Japan. This animal is an interesting and rich source of triterpene glycosides with unique chemical structures and various biological activities. The objective of this study was to investigate composition and distribution in various body components of triterpene glycosides of the sea cucumber E. fraudatrix. We applied LC-ESI MS (liquid chromatography–electrospray mass spectrometry) of whole body extract and extracts of various body components for metabolic profiling and structure elucidation of triterpene glycosides from the E. fraudatrix. Totally, 54 compounds, including 26 sulfated, 18 non-sulfated and 10 disulfated glycosides were detected and described. Triterpene glycosides from the body walls, gonads, aquapharyngeal bulbs, guts and respiratory trees were extracted separately and the distributions of the detected compounds in various body components were analyzed. Series of new glycosides with unusual structural features were described in E. fraudatrix, which allow clarifying the biosynthesis of these compounds. Comparison of the triterpene glycosides contents from the five different body components revealed that the profiles of triterpene glycosides were qualitatively similar, and only some quantitative variabilities for minor compounds were observed. Full article

(This article belongs to the Special Issue Marine Glycosides)

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Open AccessArticle

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice

by Natalia Anisimova, Nadezhda Ustyuzhanina, Maria Bilan, Fedor Donenko, Anatolii Usov, Mikhail Kiselevskiy and Nikolay Nifantiev

Mar. Drugs 2017, 15(10), 301; https://doi.org/10.3390/md15100301 - 30 Sep 2017

Cited by 25 | Viewed by 5218

Abstract

Application of cytostatics in cancer patients’ chemotherapy results in a number of side effects, including the inhibition of various parts of hematopoiesis. Two sulfated polysaccharides, fucoidan from the seaweed Chordaria flagelliformis (PS-Fuc) and fucosylated chondroitin sulfate from the sea cucumber Massinium [...] Read more.

Application of cytostatics in cancer patients’ chemotherapy results in a number of side effects, including the inhibition of various parts of hematopoiesis. Two sulfated polysaccharides, fucoidan from the seaweed Chordaria flagelliformis (PS-Fuc) and fucosylated chondroitin sulfate from the sea cucumber Massinium magnum (PS-FCS), were studied as stimulators of hematopoiesis after cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF) was applied as a reference. Both tested polysaccharides PS-Fuc and PS-FCS have a similar activity to r G-CSF, causing pronounced neutropoiesis stimulation in animals with myelosuppression induced by cyclophosphamide (CPh). Moreover, these compounds are also capable to enhance thrombopoiesis and erythropoiesis. It should be noted that PS-FCS demonstrated a greater activity than r G-CSF. The results indicate the perspective of further studies of PS-Fuc and PS-FCS, since these compounds can be considered as potentially promising stimulators of hematopoiesis. Such drugs are in demand for the accompanying treatment of cancer patients who suffer from hematological toxicity during chemo and/or radiation therapy. Full article

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Open AccessArticle

Anti-Inflammatory Lobane and Prenyleudesmane Diterpenoids from the Soft Coral Lobophytum varium

by Atallah F. Ahmed, Wan-Ting Teng, Chiung-Yao Huang, Chang-Feng Dai, Tsong-Long Hwang and Jyh-Horng Sheu

Mar. Drugs 2017, 15(10), 300; https://doi.org/10.3390/md15100300 - 29 Sep 2017

Cited by 14 | Viewed by 5763

Abstract

New lobane-based diterpenoids lobovarols A–D (1–4) and a prenyleudesmane-type diterpenoid lobovarol E (5) along with seven known related diterpenoids (6–12) were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum [...] Read more.

New lobane-based diterpenoids lobovarols A–D (1–4) and a prenyleudesmane-type diterpenoid lobovarol E (5) along with seven known related diterpenoids (6–12) were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum varium. Their structures were identified on the basis of multiple spectroscopic analyses and spectral comparison. The absolute configuration at C-16 of the known compound 11 is reported herein for the first time. The anti-inflammatory activities of compounds 1–12 were assessed by measuring their inhibitory effect on N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils. Metabolites 2, 5, and 11 were found to show moderate inhibitory activity on the generation of superoxide anion, while compounds 5, 8, 11, and 12 could effectively suppress elastase release in fMLP/CB-stimulated human neutrophil cells at 10 μM. All of the isolated diterpenoids did not exhibit cytotoxic activity (IC₅₀ > 50 μM) towards a limited panel of cancer cell lines. Full article

(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)

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