Marine Drugs

9 pages, 3600 KB

Open AccessArticle

Mass Spectrometric Characteristics of Prenylated Indole Derivatives from Marine-Derived Penicillium sp. NH-SL

by Hui Ding, Wanjing Ding and Zhongjun Ma

Mar. Drugs 2017, 15(3), 86; https://doi.org/10.3390/md15030086 - 22 Mar 2017

Cited by 7 | Viewed by 4618

Two prenylated indole alkaloids were isolated from the ethyl acetate extracts of a marine-derived fungus Penicillium sp. NH-SL and one of them exhibited potent cytotoxic activity against mouse hepa 1c1c7 cells. In order to detect other bioactive analogs, we used liquid chromatogram tandem [...] Read more.

Two prenylated indole alkaloids were isolated from the ethyl acetate extracts of a marine-derived fungus Penicillium sp. NH-SL and one of them exhibited potent cytotoxic activity against mouse hepa 1c1c7 cells. In order to detect other bioactive analogs, we used liquid chromatogram tandem mass spectrometry (LC-MS/MS) to analyze the mass spectrometric characteristics of the isolated compounds as well as the crude extracts. As a result, three other analogs were detected, and their structures were deduced according to the similar fragmentation patterns. This is the first systematic report on the mass spectrometric characteristics of prenylated indole derivatives. Full article

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19 pages, 3420 KB

Open AccessArticle

An Extract from Shrimp Processing By-Products Protects SH-SY5Y Cells from Neurotoxicity Induced by Aβ_25–35

by Yongping Zhang, Guangling Jiao, Cai Song, Shelly Gu, Richard E. Brown, Junzeng Zhang, Pingcheng Zhang, Jacques Gagnon, Steven Locke, Roumiana Stefanova, Claude Pelletier, Yi Zhang and Hongyu Lu

Mar. Drugs 2017, 15(3), 83; https://doi.org/10.3390/md15030083 - 22 Mar 2017

Cited by 24 | Viewed by 7514

Abstract

Increased evidence suggests that marine unsaturated fatty acids (FAs) can protect neurons from amyloid-β (Aβ)-induced neurodegeneration. Nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and gas chromatography (GC) assays showed that the acetone extract 4-2A obtained from shrimp Pandalus borealis industry processing [...] Read more.

Increased evidence suggests that marine unsaturated fatty acids (FAs) can protect neurons from amyloid-β (Aβ)-induced neurodegeneration. Nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and gas chromatography (GC) assays showed that the acetone extract 4-2A obtained from shrimp Pandalus borealis industry processing wastes contained 67.19% monounsaturated FAs and 16.84% polyunsaturated FAs. The present study evaluated the anti-oxidative and anti-inflammatory effects of 4-2A in Aβ_25–35-insulted differentiated SH-SY5Y cells. Cell viability and cytotoxicity were measured by using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Quantitative PCR and Western blotting were used to study the expression of neurotrophins, pro-inflammatory cytokines and apoptosis-related genes. Administration of 20 μM Aβ_25–35 significantly reduced SH-SY5Y cell viability, the expression of nerve growth factor (NGF) and its tyrosine kinase TrkA receptor, as well as the level of glutathione, while increased reactive oxygen species (ROS), nitric oxide, tumor necrosis factor (TNF)-α, brain derived neurotrophic factor (BDNF) and its TrkB receptor. Aβ_25–35 also increased the Bax/Bcl-2 ratio and Caspase-3 expression. Treatment with 4-2A significantly attenuated the Aβ_25–35-induced changes in cell viability, ROS, GSH, NGF, TrkA, TNF-α, the Bax/Bcl-2 ratio and Caspase-3, except for nitric oxide, BDNF and TrKB. In conclusion, 4-2A effectively protected SH-SY5Y cells against Aβ-induced neuronal apoptosis/death by suppressing inflammation and oxidative stress and up-regulating NGF and TrKA expression. Full article

(This article belongs to the Special Issue Marine Lipids 2017)

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16 pages, 3005 KB

Open AccessArticle

Biosynthesis of Polyunsaturated Fatty Acids in Octopus vulgaris: Molecular Cloning and Functional Characterisation of a Stearoyl-CoA Desaturase and an Elongation of Very Long-Chain Fatty Acid 4 Protein

by Óscar Monroig, Rosa De Llanos, Inmaculada Varó, Francisco Hontoria, Douglas R. Tocher, Sergi Puig and Juan C. Navarro

Mar. Drugs 2017, 15(3), 82; https://doi.org/10.3390/md15030082 - 21 Mar 2017

Cited by 45 | Viewed by 7183

Abstract

Polyunsaturated fatty acids (PUFAs) have been acknowledged as essential nutrients for cephalopods but the specific PUFAs that satisfy the physiological requirements are unknown. To expand our previous investigations on characterisation of desaturases and elongases involved in the biosynthesis of PUFAs and hence determine [...] Read more.

Polyunsaturated fatty acids (PUFAs) have been acknowledged as essential nutrients for cephalopods but the specific PUFAs that satisfy the physiological requirements are unknown. To expand our previous investigations on characterisation of desaturases and elongases involved in the biosynthesis of PUFAs and hence determine the dietary PUFA requirements in cephalopods, this study aimed to investigate the roles that a stearoyl-CoA desaturase (Scd) and an elongation of very long-chain fatty acid 4 (Elovl4) protein play in the biosynthesis of essential fatty acids (FAs). Our results confirmed the Octopus vulgaris Scd is a ∆9 desaturase with relatively high affinity towards saturated FAs with ≥ C₁₈ chain lengths. Scd was unable to desaturate 20:1n-15 (^∆520:1) suggesting that its role in the biosynthesis of non-methylene interrupted FAs (NMI FAs) is limited to the introduction of the first unsaturation at ∆9 position. Interestingly, the previously characterised ∆5 fatty acyl desaturase was indeed able to convert 20:1n-9 (^∆1120:1) to ^∆5,1120:2, an NMI FA previously detected in octopus nephridium. Additionally, Elovl4 was able to mediate the production of 24:5n-3 and thus can contribute to docosahexaenoic acid (DHA) biosynthesis through the Sprecher pathway. Moreover, the octopus Elovl4 was confirmed to play a key role in the biosynthesis of very long-chain (>C₂₄) PUFAs. Full article

(This article belongs to the Special Issue Marine Lipids 2017)

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25 pages, 3209 KB

Open AccessReview

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

by Palma Lamonaca, Giulia Prinzi, Aliaksei Kisialiou, Vittorio Cardaci, Massimo Fini and Patrizia Russo

Mar. Drugs 2017, 15(3), 81; https://doi.org/10.3390/md15030081 - 20 Mar 2017

Cited by 15 | Viewed by 9001

Abstract

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity [...] Read more.

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI). Full article

(This article belongs to the Special Issue Marine Natural Products that Target Metabolic Disorders)

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18 pages, 1612 KB

Open AccessArticle

Bioactive Potential of Marine Macroalgae from the Central Red Sea (Saudi Arabia) Assessed by High-Throughput Imaging-Based Phenotypic Profiling

by Stephan Kremb, Constanze Müller, Philippe Schmitt-Kopplin and Christian R. Voolstra

Mar. Drugs 2017, 15(3), 80; https://doi.org/10.3390/md15030080 - 20 Mar 2017

Cited by 17 | Viewed by 7332

Abstract

Marine algae represent an important source of novel natural products. While their bioactive potential has been studied to some extent, limited information is available on marine algae from the Red Sea. This study aimed at the broad discovery of new bioactivities from a [...] Read more.

Marine algae represent an important source of novel natural products. While their bioactive potential has been studied to some extent, limited information is available on marine algae from the Red Sea. This study aimed at the broad discovery of new bioactivities from a collection of twelve macroalgal species from the Central Red Sea. We used imaging-based High-Content Screening (HCS) with a diverse spectrum of cellular markers for detailed cytological profiling of fractionated algal extracts. The cytological profiles for 3 out of 60 algal fractions clustered closely to reference inhibitors and showed strong inhibitory activities on the HIV-1 reverse transcriptase in a single-enzyme biochemical assay, validating the suggested biological target. Subsequent chemical profiling of the active fractions of two brown algal species by ultra-high resolution mass spectrometry (FT-ICR-MS) revealed possible candidate molecules. A database query of these molecules led us to groups of compounds with structural similarities, which are suggested to be responsible for the observed activity. Our work demonstrates the versatility and power of cytological profiling for the bioprospecting of unknown biological resources and highlights Red Sea algae as a source of bioactives that may serve as a starting point for further studies. Full article

(This article belongs to the Special Issue Marine Natural Product Discovery: Innovative Strategies and Future Trends)

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13 pages, 3383 KB

Open AccessArticle

Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

by Rebeca Cristina Costa Pereira, André Luiz Lourenço, Luciana Terra, Paula Alvarez Abreu, Valéria Laneuville Teixeira and Helena Carla Castro

Mar. Drugs 2017, 15(3), 79; https://doi.org/10.3390/md15030079 - 20 Mar 2017

Cited by 22 | Viewed by 6408

Abstract

Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol [...] Read more.

Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents. Full article

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16 pages, 2203 KB

Open AccessReview

Phakellistatins: An Underwater Unsolved Puzzle

by Alessandra Meli, Consiglia Tedesco, Giorgio Della Sala, Rosaria Schettini, Fernando Albericio, Francesco De Riccardis and Irene Izzo

Mar. Drugs 2017, 15(3), 78; https://doi.org/10.3390/md15030078 - 18 Mar 2017

Cited by 30 | Viewed by 5871

Abstract

A critical summary on the discovery of the nineteen members of the phakellistatin family (phakellistatin 1–19), cytotoxic proline-rich cyclopeptides of marine origin, is reported. Isolation, structural elucidation, and biological properties of the various-sized natural macrocycles are described, along with the [...] Read more.

A critical summary on the discovery of the nineteen members of the phakellistatin family (phakellistatin 1–19), cytotoxic proline-rich cyclopeptides of marine origin, is reported. Isolation, structural elucidation, and biological properties of the various-sized natural macrocycles are described, along with the total syntheses and the enigmatic issues of the cytotoxic activity reproducibility. Full article

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13 pages, 4169 KB

Open AccessArticle

Protective Effects of Fucoidan on Aβ25–35 and d-Gal-Induced Neurotoxicity in PC12 Cells and d-Gal-Induced Cognitive Dysfunction in Mice

by Hengyun Wei, Zixiang Gao, Luping Zheng, Cuili Zhang, Zundong Liu, Yazong Yang, Hongming Teng, Lin Hou, Yuling Yin and Xiangyang Zou

Mar. Drugs 2017, 15(3), 77; https://doi.org/10.3390/md15030077 - 16 Mar 2017

Cited by 102 | Viewed by 7524

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells [...] Read more.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease which contributes to memory loss and cognitive decline in the elderly. Fucoidan, extracted from brown algae, is a complex sulfated polysaccharide and potential bioactive compound. In this study, we investigated whether fucoidan protects PC12 cells from apoptosis induced by a combination of beta-amyloid 25–35 (Aβ25–35) and d-galactose (d-Gal), and improves learning and memory impairment in AD model mice. The results indicated that fucoidan could inhibit the release of cytochrome c from the mitochondria to cytosol and activation of caspases, and increase the expression of apoptosis inhibitor proteins (IAPs), including livin and X-linked IAP (XIAP) in PC12 cells damaged by Aβ25–35 and d-Gal-induction. Fucoidan reversed the decreased activity of acetylcholine (ACh) and choline acetyl transferase (ChAT), as well as the increased activity of acetylcholine esterase (AChE), in AD model mice induced by infusion of d-Gal. Furthermore, fucoidan improved antioxidant activity in vitro and in vivo by activation of superoxide dismutase (SOD) and glutathione (GSH). These results suggested that fucoidan could protect PC12 cells from apoptosis and ameliorate the learning and memory impairment in AD model mice, which appeared to be due to regulating the cholinergic system, reducing oxidative stress, and inhibiting the caspase-dependent apoptosis pathway. Full article

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14 pages, 1914 KB

Open AccessArticle

Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6

by Hui Ding, Dashan Zhang, Biao Zhou and Zhongjun Ma

Mar. Drugs 2017, 15(3), 76; https://doi.org/10.3390/md15030076 - 16 Mar 2017

Cited by 28 | Viewed by 5954

Abstract

Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein–protein interaction inhibitors have [...] Read more.

Bromodomains (BRD) are readers of the epigenetic code that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Recently, bromodomain-containing proteins such as BRD4 have been demonstrated to be druggable through the discovery of potent inhibitors. These protein–protein interaction inhibitors have the potential to modulate multiple diseases by their profound anti-inflammatory and antiproliferative effects. In order to explore new BRD4 inhibitors as well as lead compounds for the development of new drugs, the secondary metabolites of Alternaria sp. NH-F6, a fungus isolated from deep-sea sediment samples, were analyzed systematically. Five new compounds including two new perylenequinones (1–2), one new alternaric acid (3), 2-(N-vinylacetamide)-4-hydroxymethyl-3-ene-butyrolactone (4), one new cerebroside (5), together with 19 known compounds (6–24) were isolated from the ethyl acetate extracts of this strain. Their structures were elucidated using nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses. Finally, all these compounds were evaluated for their inhibitory activity against BRD4 protein, and compound 2 exhibited a potent inhibition rate of 88.1% at a concentration of 10 µM. This research provides a new BRD4 inhibitor which may possess potential antitumoral, antiviral, or anti-inflammatory pharmaceutical values. Full article

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10 pages, 2182 KB

Open AccessFeature PaperArticle

FUSION-Guided Hypothesis Development Leads to the Identification of N⁶,N⁶-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor

by Rachel M. Vaden, Nathaniel W. Oswald, Malia B. Potts, John B. MacMillan and Michael A. White

Mar. Drugs 2017, 15(3), 75; https://doi.org/10.3390/md15030075 - 15 Mar 2017

Cited by 13 | Viewed by 5914

Abstract

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit [...] Read more.

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism. Using Functional Signature Ontology (FUSION), we report the parallel isolation and characterization of a marine-derived natural product, N⁶,N⁶-dimethyladenosine, that robustly inhibits AKT signaling in a variety of non-small cell lung cancer cell lines. Upon validation of the elucidated structure by comparison with a commercially available sample, experiments were initiated to understand the small molecule’s breadth of effect in a biological setting. One such experiment, a reverse phase protein array (RPPA) analysis of >50 kinases, indicated a specific cellular response to treatment. In all, leveraging the FUSION platform allowed for the rapid generation and validation of a biological mechanism of action hypothesis for an unknown natural product and permitted accelerated purification of the bioactive component from a chemically complex fraction. Full article

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

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12 pages, 2878 KB

Open AccessArticle

Krill Oil-In-Water Emulsion Protects against Lipopolysaccharide-Induced Proinflammatory Activation of Macrophages In Vitro

by Gabriel A. Bonaterra, David Driscoll, Hans Schwarzbach and Ralf Kinscherf

Mar. Drugs 2017, 15(3), 74; https://doi.org/10.3390/md15030074 - 15 Mar 2017

Cited by 35 | Viewed by 6521

Abstract

Background: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. [...] Read more.

Background: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro. Materials and Methods: Differentiated THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4) in order to determine the inhibitory properties of the KO emulsion on the LPS-binding capacity, and the subsequent release of TNF-α. Results: KO emulsion inhibited the macrophage binding of LPS to the TLR4 by 50% (at 12.5 µg/mL) and 75% (at 25 µg/mL), whereas, at 50 µg/mL, completely abolished the LPS binding. Moreover, KO (12.5 µg/mL, 25 µg/mL, or 50 µg/mL) also inhibited (30%, 40%, or 75%, respectively) the TNF-α release after activation with 0.01 µg/mL LPS in comparison with LPS treatment alone. Conclusion: KO emulsion influences the LPS-induced pro-inflammatory activation of macrophages, possibly due to inactivation of the LPS binding capacity. Full article

(This article belongs to the Special Issue Marine Lipids 2017)

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13 pages, 3303 KB

Open AccessArticle

Marine Lectins DlFBL and HddSBL Fused with Soluble Coxsackie-Adenovirus Receptor Facilitate Adenovirus Infection in Cancer Cells BUT Have Different Effects on Cell Survival

by Bingbing Wu, Shengsheng Mei, Lianzhen Cui, Zhenzhen Zhao, Jianhong Chen, Tao Wu and Gongchu Li

Mar. Drugs 2017, 15(3), 73; https://doi.org/10.3390/md15030073 - 14 Mar 2017

Cited by 13 | Viewed by 5331

Abstract

Cancer development and progression are usually associated with glycosylation change, providing prognostic and diagnostic biomarkers, as well as therapeutic targets, for various cancers. In this work, Dicentrarchus labrax fucose binding lectin (DlFBL) and Haliotis discus discus sialic acid binding lectin (HddSBL) were genetically [...] Read more.

Cancer development and progression are usually associated with glycosylation change, providing prognostic and diagnostic biomarkers, as well as therapeutic targets, for various cancers. In this work, Dicentrarchus labrax fucose binding lectin (DlFBL) and Haliotis discus discus sialic acid binding lectin (HddSBL) were genetically fused with soluble coxsackie-adenovirus receptor (sCAR), and produced through a bacterial expression system. Results showed that recombinant sCAR-DlFBL not only facilitated adenovirus Ad-EGFP infection in K562/ADR and U87MG cells, but also enhanced the cytotoxicity of adenovirus harboring gene encoding Pinellia pedatisecta agglutinin (PPA) or DlFBL (Ad-PPA or Ad-DlFBL) on U87MG cells through inducing apoptosis. Recombinant sCAR-HddSBL facilitated Ad-EGFP infection, but dramatically counteracted the cytotoxicity of both Ad-PPA and Ad-DlFBL in U87MG cells. Further analysis revealed that sCAR-HddSBL, but not sCAR-DlFBL, significantly upregulated transcription factor E2F1 levels in U87MG cells, which might be responsible for the adverse effect of sCAR-HddSBL on Ad-PPA and Ad-DlFBL. Taken together, our data suggested that sCAR-DlFBL could be further developed to redirect therapeutic adenoviruses to infect cancer cells such as U87MG, and the sCAR-lectin fusion proteins for adenoviral retargeting should be carefully examined for possible survival signaling induced by lectins, such as HddSBL. Full article

(This article belongs to the Special Issue Structures, Functions and Applications of Marine Lectins)

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41 pages, 421 KB

Open AccessFeature PaperReview

An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

by Melissa A. Friedman, Mercedes Fernandez, Lorraine C. Backer, Robert W. Dickey, Jeffrey Bernstein, Kathleen Schrank, Steven Kibler, Wendy Stephan, Matthew O. Gribble, Paul Bienfang, Robert E. Bowen, Stacey Degrasse, Harold A. Flores Quintana, Christopher R. Loeffler, Richard Weisman, Donna Blythe, Elisa Berdalet, Ram Ayyar, Danielle Clarkson-Townsend, Karen Swajian, Ronald Benner, Tom Brewer and Lora E. Fleming Show full author list Hide full author list

Mar. Drugs 2017, 15(3), 72; https://doi.org/10.3390/md15030072 - 14 Mar 2017

Cited by 279 | Viewed by 28384

Abstract

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or [...] Read more.

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties. Full article

(This article belongs to the Special Issue Marine Neurotoxins)

8 pages, 806 KB

Open AccessArticle

Anti-Allergic Compounds from the Deep-Sea-Derived Actinomycete Nesterenkonia flava MCCC 1K00610

by Chun-Lan Xie, Qingmei Liu, Jin-Mei Xia, Yuanyuan Gao, Quan Yang, Zong-Ze Shao, Guangming Liu and Xian-Wen Yang

Mar. Drugs 2017, 15(3), 71; https://doi.org/10.3390/md15030071 - 14 Mar 2017

Cited by 47 | Viewed by 7872

Abstract

A novel cyclic ether, nesterenkoniane (1), was isolated from the deep-sea-derived actinomycete Nesterenkonia flava MCCC 1K00610, together with 12 known compounds, including two macrolides (2, 3), two diketopiperazines (4, 5), two nucleosides (6, [...] Read more.

A novel cyclic ether, nesterenkoniane (1), was isolated from the deep-sea-derived actinomycete Nesterenkonia flava MCCC 1K00610, together with 12 known compounds, including two macrolides (2, 3), two diketopiperazines (4, 5), two nucleosides (6, 7), two indoles (8, 9), three phenolics (10–12), and one butanol derivate (13). Their structures were established mainly on detailed analysis of the NMR and MS spectroscopic data. All 13 compounds were tested for anti-allergic activities using immunoglobulin E (IgE) mediated rat mast RBL-2H3 cell model. Under the concentration of 20 μg/mL, 1 exhibited moderate anti-allergic activity with inhibition rate of 9.86%, compared to that of 37.41% of the positive control, loratadine. While cyclo(d)-Pro-(d)-Leu (4) and indol-3-carbaldehyde (8) showed the most potent effects with the IC₅₀ values of 69.95 and 57.12 μg/mL, respectively, which was comparable to that of loratadine (IC₅₀ = 35.01 μg/mL). To the best of our knowledge, it is the first report on secondary metabolites from the genus of Nesterenkonia. Full article

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

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15 pages, 906 KB

Open AccessArticle

Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery

by Yang Qu, Jinyu Xu, Haohan Zhou, Rongpeng Dong, Mingyang Kang and Jianwu Zhao

Mar. Drugs 2017, 15(3), 70; https://doi.org/10.3390/md15030070 - 14 Mar 2017

Cited by 13 | Viewed by 5966

Abstract

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide [...] Read more.

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG (p < 0.05), respectively. COS reduces the side effects caused by antibiotics (p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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10 pages, 1266 KB

Open AccessArticle

New Metabolites and Bioactive Chlorinated Benzophenone Derivatives Produced by a Marine-Derived Fungus Pestalotiopsis heterocornis

by Hui Lei, Xiuping Lin, Li Han, Jian Ma, Qingjuan Ma, Jialiang Zhong, Yonghong Liu, Tiemin Sun, Jinhui Wang and Xueshi Huang

Mar. Drugs 2017, 15(3), 69; https://doi.org/10.3390/md15030069 - 13 Mar 2017

Cited by 44 | Viewed by 6656

Abstract

Four new compounds, including two isocoumarins, pestaloisocoumarins A and B (1, 2), one sesquiterpenoid degradation, isopolisin B (4), and one furan derivative, pestalotiol A (5), together with one known isocoumarin, gamahorin (3), and three [...] Read more.

Four new compounds, including two isocoumarins, pestaloisocoumarins A and B (1, 2), one sesquiterpenoid degradation, isopolisin B (4), and one furan derivative, pestalotiol A (5), together with one known isocoumarin, gamahorin (3), and three chlorinated benzophenone derivatives, pestalachloride B (6), pestalachloride E (7) and a mixture of pestalalactone atropisomers (8a/8b), were isolated from a culture of the fungus Pestalotiopsis heterocornis associated with sponge Phakellia fusca. These new chemical structures were established using NMR and MS spectroscopic data, as well as single-crystal X-ray crystallographic analysis and CD Cotton effects. All of the isolated compounds were evaluated for their antimicrobial and cytotoxic activities. Isocoumarins 1–3, showed antibacterial activities against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 25 to 100 μg/mL and weak antifungal activities. Chlorinated benzophenone derivatives 6–8 exhibited antibacterial activities against S. aureus and B. subtilis with MIC values ranging from 3.0 to 50 μg/mL and cytotoxicities against four human cancer cell lines with IC₅₀ values of 6.8–87.8 μM. Full article

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13 pages, 3401 KB

Open AccessReview

Cytotoxic Natural Products from Marine Sponge-Derived Microorganisms

by Huawei Zhang, Ziping Zhao and Hong Wang

Mar. Drugs 2017, 15(3), 68; https://doi.org/10.3390/md15030068 - 10 Mar 2017

Cited by 61 | Viewed by 10807

Abstract

A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last [...] Read more.

A growing body of evidence indicates that marine sponge-derived microbes possess the potential ability to make prolific natural products with therapeutic effects. This review for the first time provides a comprehensive overview of new cytotoxic agents from these marine microbes over the last 62 years from 1955 to 2016, which are assorted into seven types: terpenes, alkaloids, peptides, aromatics, lactones, steroids, and miscellaneous compounds. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes - II)

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23 pages, 760 KB

Open AccessFeature PaperReview

Bioactive Peptide of Marine Origin for the Prevention and Treatment of Non-Communicable Diseases

by Ratih Pangestuti and Se-Kwon Kim

Mar. Drugs 2017, 15(3), 67; https://doi.org/10.3390/md15030067 - 9 Mar 2017

Cited by 85 | Viewed by 10611

Abstract

Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms [...] Read more.

Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms are considered as an important source of bioactive peptides that can exert biological functions to prevent and treatment of NCD. Recent pharmacological investigations reported cardio protective, anticancer, antioxidative, anti-diabetic, and anti-obesity effects of marine-derived bioactive peptides. Moreover, there is available evidence supporting the utilization of marine organisms and its bioactive peptides to alleviate NCD. Marine-derived bioactive peptides are alternative sources for synthetic ingredients that can contribute to a consumer’s well-being, as a part of nutraceuticals and functional foods. This contribution focus on the bioactive peptides derived from marine organisms and elaborates its possible prevention and therapeutic roles in NCD. Full article

(This article belongs to the Special Issue Marine Proteins and Peptides)

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15 pages, 4369 KB

Open AccessArticle

Astaxanthin Inhibits PC-3 Xenograft Prostate Tumor Growth in Nude Mice

by Xiaofeng Ni, Haining Yu, Shanshan Wang, Chengcheng Zhang and Shengrong Shen

Mar. Drugs 2017, 15(3), 66; https://doi.org/10.3390/md15030066 - 8 Mar 2017

Cited by 47 | Viewed by 11090

Abstract

Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, [...] Read more.

Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, astaxanthin has been demonstrated to exert beneficial effects against inflammation, cardiovascular disease, oxidative damage, or different cancer sites. This study used intragastric administration of astaxanthin to detect its role on tumor proliferation, apoptosis, microRNA (miRNA) overexpression, and microbacteria composition change by establishing androgen-independent PCa cell PC-3 xenograft nude mice. Nude mice were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. The intervention was started when tumors reached 0.5–0.6 cm in diameter. Mice were intragastrically administered 100 mg/kg astaxanthin (HA), 25 mg/kg astaxanthin (LA), or olive oil (TC). The results showed that 100 mg/kg astaxanthin significantly inhibited tumor growth compared to the TC group, with an inhibitory rate of 41.7%. A decrease of Ki67 and proliferating cell nuclear antigen (PCNA) as well as an increase of cleaved caspase-3 were observed in HA-treated tumors, along with increasing apoptotic cells, obtained by TUNEL assay. The HA significantly elevated the levels of tumor suppressors miR-375 and miR-487b in tumor tissues and the amount of Lactobacillus sp. and Lachnospiraceae in mice stools, while there was no significant difference between LA and TC groups. These results provide a promising regimen to enhance the therapeutic effect in a dietary supplement manner. Full article

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18 pages, 4836 KB

Open AccessArticle

The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA

by Agnieszka Śmieszek, Ewa Giezek, Martyna Chrapiec, Martyna Murat, Aleksandra Mucha, Izabela Michalak and Krzysztof Marycz

Mar. Drugs 2017, 15(3), 65; https://doi.org/10.3390/md15030065 - 7 Mar 2017

Cited by 39 | Viewed by 9837

Abstract

Spirulina platensis (SP) is a blue-green microalga that has recently raised attention not only as a nutritional component, but also as a source of bioactivities that have therapeutic effects and may find application in medicine, including cancer treatment. In the present study we [...] Read more.

Spirulina platensis (SP) is a blue-green microalga that has recently raised attention not only as a nutritional component, but also as a source of bioactivities that have therapeutic effects and may find application in medicine, including cancer treatment. In the present study we determined the cytotoxic effect of S. platensis filtrates (SPF) on human colon cancer cell line Caco-2. Three concentrations of SPF were tested—1.25%, 2.5%, and 5% (v/v). We have found that the highest concentration of SPF exerts the strongest anti-proliferative and pro-apoptotic effect on Caco-2 cultures. The SPF negatively affected the morphology of Caco-2 causing colony shrinking and significant inhibition of metabolic and proliferative activity of cells. The wound-healing assay showed that the SPF impaired migratory capabilities of Caco-2. This observation was consistent with lowered mRNA levels for metalloproteinases. Furthermore, SPF decreased the transcript level of pro-survival genes (cyclin D1, surviving, and c-Myc) and reduced the autocrine secretion of Wnt-10b. The cytotoxic effect of SPF involved the modulation of the Bax and Bcl-2 ratio and a decrease of mitochondrial activity, and was related with increased levels of intracellular reactive oxygen species (ROS) and nitric oxide (NO). Moreover, the SPF also caused an increased number of cells in the apoptotic sub-G0 phase and up-regulated expression of mir-145, simultaneously decreasing expression of mir-17 and 146. Obtained results indicate that SPF can be considered as an agent with anti-cancer properties that may be used for colon cancer prevention and treatment. Full article

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12 pages, 1517 KB

Open AccessArticle

Chitosan-Based Nanomedicine to Fight Genital Candida Infections: Chitosomes

by Toril Andersen, Ekaterina Mishchenko, Gøril Eide Flaten, Johanna U. Ericson Sollid, Sofia Mattsson, Ingunn Tho and Nataša Škalko-Basnet

Mar. Drugs 2017, 15(3), 64; https://doi.org/10.3390/md15030064 - 4 Mar 2017

Cited by 50 | Viewed by 9699

Abstract

Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great [...] Read more.

Vaginal infections are associated with high recurrence, which is often due to a lack of efficient treatment of complex vaginal infections comprised of several types of pathogens, especially fungi and bacteria. Chitosan, a mucoadhesive polymer with known antifungal effect, could offer a great improvement in vaginal therapy; the chitosan-based nanosystem could both provide antifungal effects and simultaneously deliver antibacterial drugs. We prepared chitosan-containing liposomes, chitosomes, where chitosan is both embedded in liposomes and surface-available as a coating layer. For antimicrobial activity, we entrapped metronidazole as a model drug. To prove that mucoadhesivness alone is not sufficient for successful delivery, we used Carbopol-containing liposomes as a control. All vesicles were characterized for their size, zeta potential, entrapment efficiency, and in vitro drug release. Chitosan-containing liposomes were able to assure the prolonged release of metronidazole. Their antifungal activity was evaluated in a C. albicans model; chitosan-containing liposomes exhibited a potent ability to inhibit the growth of C. albicans. The presence of chitosan was crucial for the system’s antifungal activity. The antifungal efficacy of chitosomes combined with antibacterial potential of the entrapped metronidazole could offer improved efficacy in the treatment of mixed/complex vaginal infections. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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11 pages, 592 KB

Open AccessArticle

Cytotoxicity of Endoperoxides from the Caribbean Sponge Plakortis halichondrioides towards Sensitive and Multidrug-Resistant Leukemia Cells: Acids vs. Esters Activity Evaluation

by Tanja Schirmeister, Swarna Oli, Hongmei Wu, Gerardo Della Sala, Valeria Costantino, Ean-Jeong Seo and Thomas Efferth

Mar. Drugs 2017, 15(3), 63; https://doi.org/10.3390/md15030063 - 3 Mar 2017

Cited by 11 | Viewed by 6102

Abstract

The 6-epimer of the plakortide H acid (1), along with the endoperoxides plakortide E (2), plakortin (3), and dihydroplakortin (4) have been isolated from a sample of the Caribbean sponge Plakortis halichondrioides. To perform [...] Read more.

The 6-epimer of the plakortide H acid (1), along with the endoperoxides plakortide E (2), plakortin (3), and dihydroplakortin (4) have been isolated from a sample of the Caribbean sponge Plakortis halichondrioides. To perform a comparative study on the cytotoxicity towards the drug-sensitive leukemia CCRF-CEM cell line and its multi-drug resistant subline CEM/ADR5000, the acid of plakortin, namely plakortic acid (5), as well as the esters plakortide E methyl ester (6) and 6-epi-plakortide H (7) were synthesized by hydrolysis and Steglich esterification, respectively. The data obtained showed that the acids (1, 2, 5) exhibited potent cytotoxicity towards both cell lines, whereas the esters showed no activity (6, 7) or weaker activity (3, 4) compared to their corresponding acids. Plakortic acid (5) was the most promising derivative with half maximal inhibitory concentration (IC₅₀₎ values of ca. 0.20 µM for both cell lines. Full article

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

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17 pages, 2100 KB

Open AccessFeature PaperArticle

Valorization of Lipids from Gracilaria sp. through Lipidomics and Decoding of Antiproliferative and Anti-Inflammatory Activity

by Elisabete Da Costa, Tânia Melo, Ana S. P. Moreira, Carina Bernardo, Luisa Helguero, Isabel Ferreira, Maria Teresa Cruz, Andreia M. Rego, Pedro Domingues, Ricardo Calado, Maria H. Abreu and Maria Rosário Domingues

Mar. Drugs 2017, 15(3), 62; https://doi.org/10.3390/md15030062 - 2 Mar 2017

Cited by 81 | Viewed by 9455

Abstract

The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS). One hundred and forty-seven molecular species were identified [...] Read more.

The lipidome of the red seaweed Gracilaria sp., cultivated on land-based integrated multitrophic aquaculture (IMTA) system, was assessed for the first time using hydrophilic interaction liquid chromatography-mass spectrometry and tandem mass spectrometry (HILIC–MS and MS/MS). One hundred and forty-seven molecular species were identified in the lipidome of the Gracilaria genus and distributed between the glycolipids classes monogalactosyl diacylglyceride (MGDG), digalactosyl diacylglyceride (DGDG), sulfoquinovosyl monoacylglyceride (SQMG), sulfoquinovosyl diacylglyceride (SQDG), the phospholipids phosphatidylcholine (PC), lyso-PC, phosphatidylglycerol (PG), lyso-PG, phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatic acid (PA), inositolphosphoceramide (IPC), and betaine lipids monoacylglyceryl- and diacylglyceryl-N,N,N-trimethyl homoserine (MGTS and DGTS). Antiproliferative and anti-inflammatory effects promoted by lipid extract of Gracilaria sp. were evaluated by monitoring cell viability in human cancer lines and by using murine macrophages, respectively. The lipid extract decreased cell viability of human T-47D breast cancer cells and of 5637 human bladder cancer cells (estimated half-maximal inhibitory concentration (IC₅₀) of 12.2 μg/mL and 12.9 μg/mL, respectively) and inhibited the production of nitric oxide (NO) evoked by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) on the macrophage cell line RAW 264.7 (35% inhibition at a concentration of 100 μg/mL). These findings contribute to increase the ranking in the value-chain of Gracilaria sp. biomass cultivated under controlled conditions on IMTA systems. Full article

(This article belongs to the Special Issue Marine Lipids 2017)

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16 pages, 2034 KB

Open AccessArticle

Purification and Identification of Antioxidant Peptides from Protein Hydrolysate of Scalloped Hammerhead (Sphyrna lewini) Cartilage

by Xue-Rong Li, Chang-Feng Chi, Li Li and Bin Wang

Mar. Drugs 2017, 15(3), 61; https://doi.org/10.3390/md15030061 - 1 Mar 2017

Cited by 62 | Viewed by 7219

Abstract

The aim of this study was to purify and identify peptides with antioxidant properties from protein hydrolysate of scalloped hammerhead (Sphyrna lewini) cartilage. Cartilaginous proteins of the scalloped hammerhead were extracted by guanidine hydrochloride, and three antioxidant peptides, named enzymolysis peptide [...] Read more.

The aim of this study was to purify and identify peptides with antioxidant properties from protein hydrolysate of scalloped hammerhead (Sphyrna lewini) cartilage. Cartilaginous proteins of the scalloped hammerhead were extracted by guanidine hydrochloride, and three antioxidant peptides, named enzymolysis peptide of scalloped hammerhead cartilage A (SCPE-A), SCPE-B and SCPE-C, were subsequently isolated from the hydrolysate of the cartilaginous proteins using ultrafiltration and chromatography. The amino acid sequences of SCPE-A, SCPE-B and SCPE-C were identified as Gly-Pro-Glu (GPE), Gly-Ala-Arg-Gly-Pro-Gln (GARGPQ), and Gly-Phe-Thr-Gly-Pro-Pro-Gly-Phe-Asn-Gly (GFTGPPGFNG), with molecular weights of 301.30 Da, 584.64 Da and 950.03 Da, respectively. As per in vitro activity testing, SCPE-A, SCPE-B and SCPE-C exhibited strong scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) (half elimination ratio (EC₅₀) 2.43, 2.66 and 1.99 mg/mL), hydroxyl radicals (HO•) (EC₅₀ 0.28, 0.21 and 0.15 mg/mL), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radicals (ABTS⁺•) (EC₅₀ 0.24, 0.18 and 0.29 mg/mL), and superoxide anion radicals (

O_{2}^{-}

•) (EC₅₀ 0.10, 0.14 and 0.11 mg/mL). In addition, SCPE-A showed inhibition activity similar to butylated hydroxytoluene (BHT) in lipid peroxidation in a linoleic acid model system. The amino acid residues of Gly, Pro and Phe could positively influence the antioxidant activities of GPE, GARGPQ and GFTGPPGFNG. These results suggested that GPE, GARGPQ and GFTGPPGFNG might serve as potential antioxidants and be used as food additives and functional foods. Full article

(This article belongs to the Special Issue Marine Proteins and Peptides)

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16 pages, 1486 KB

Open AccessReview

Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics

by Seong-Chul Hong, Seung-Yup Yoo, Hyeongmin Kim and Jaehwi Lee

Mar. Drugs 2017, 15(3), 60; https://doi.org/10.3390/md15030060 - 1 Mar 2017

Cited by 49 | Viewed by 8411

Abstract

Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, [...] Read more.

Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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12 pages, 1562 KB

Open AccessArticle

Plakofuranolactone as a Quorum Quenching Agent from the Indonesian Sponge Plakortis cf. lita

by Valeria Costantino, Gerardo Della Sala, Kumar Saurav, Roberta Teta, Rinat Bar-Shalom, Alfonso Mangoni and Laura Steindler

Mar. Drugs 2017, 15(3), 59; https://doi.org/10.3390/md15030059 - 28 Feb 2017

Cited by 31 | Viewed by 6040

Abstract

There is an urgent need for novel strategies to fight drug resistance and multi-drug resistance. As an alternative to the classic antibiotic therapy, attenuation of the bacteria virulence affecting their Quorum sensing (QS) system is a promising approach. Quorum sensing (QS) is a [...] Read more.

There is an urgent need for novel strategies to fight drug resistance and multi-drug resistance. As an alternative to the classic antibiotic therapy, attenuation of the bacteria virulence affecting their Quorum sensing (QS) system is a promising approach. Quorum sensing (QS) is a genetic regulation system that allows bacteria to communicate with each other and coordinate group behaviors. A new γ-lactone that is capable of inhibiting the LasI/R QS system, plakofuranolactone (1), was discovered in the extract of the marine sponge Plakortis cf. lita, and its structure, including absolute configuration, was determined by NMR spectroscopy, MS spectrometry, and quantum-mechanical prediction of optical rotation. The quorum quenching activity of plakofuranolactone was evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075, E. coli pSB401, and C. violeaceum CV026) and was confirmed by measuring the total protease activity (a virulence factor which is under control of the LasI/R system) of the wild-type P. aeruginosa PAO1. Further research will be pursued to assess the potential of plakofuranolactone as a new antivirulence lead compound and a chemical tool to increase the knowledge in this field. Full article

(This article belongs to the Special Issue Selected Papers from the 15th International Symposium on Marine Natural Products)

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13 pages, 2029 KB

Open AccessArticle

Total Synthesis and Stereochemical Assignment of Nostosin B

by Xiaoji Wang, Junmin Feng, Zhengshuang Xu, Tao Ye, Yi Meng and Zhiyu Zhang

Mar. Drugs 2017, 15(3), 58; https://doi.org/10.3390/md15030058 - 27 Feb 2017

Cited by 5 | Viewed by 6664

Abstract

Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R‐ and S‐2‐hydroxy‐4‐(4‐hydroxy‐phenyl) butanoic acid [...] Read more.

Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R‐ and S‐2‐hydroxy‐4‐(4‐hydroxy‐phenyl) butanoic acid (Hhpba) were prepared and incorporated into the total synthesis of nostosin B, respectively. Careful comparison of the NMR spectra and optical rotation data of synthetic nostosin B (1a and 1b) with the natural product led to the unambiguous identification of the R‐configuration of the Hhpba fragment, which was further confirmed by co‐injection with the authentic sample on HPLC using both reversed phase column and the chiral AD‐RH column. Full article

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9 pages, 720 KB

Open AccessArticle

Characterization of a New Trioxilin and a Sulfoquinovosyl Diacylglycerol with Anti-Inflammatory Properties from the Dinoflagellate Oxyrrhis marina

by Eun Young Yoon, A. Reum Yang, Jaeyeon Park, Seung Joo Moon, Eun Ju Jeong and Jung-Rae Rho

Mar. Drugs 2017, 15(3), 57; https://doi.org/10.3390/md15030057 - 27 Feb 2017

Cited by 7 | Viewed by 5164

Abstract

Two new compounds—a trioxilin and a sulfoquinovosyl diacylglycerol (SQDG)—were isolated from the methanolic extract of the heterotrophic dinoflagellate Oxyrrhis marina cultivated by feeding on dried yeasts. The trioxilin was identified as (4Z,8E,13Z,16Z,19Z) -7( [...] Read more.

Two new compounds—a trioxilin and a sulfoquinovosyl diacylglycerol (SQDG)—were isolated from the methanolic extract of the heterotrophic dinoflagellate Oxyrrhis marina cultivated by feeding on dried yeasts. The trioxilin was identified as (4Z,8E,13Z,16Z,19Z) -7(S),10(S),11(S)-trihydroxydocosapentaenoic acid (1), and the SQDG was identified as (2S)-1-O-hexadecanosy-2-O-docosahexaenoyl-3-O-(6-sulfo-α-d-quinovopyranosyl)-glycerol (2) by a combination of nuclear magnetic resonance (NMR) spectra, mass analyses, and chemical reactions. The two compounds were associated with docosahexaenoic acid, which is a major component of O. marina. The two isolated compounds showed significant nitric oxide inhibitory activity on lipopolysaccharide-induced RAW264.7 cells. Compound 2 showed no cytotoxicity against hepatocarcinoma (HepG2), neuroblastoma (Neuro-2a), and colon cancer (HCT-116) cells, while weak cytotoxicity was observed for compound 1 against Neuro-2a cells. Full article

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10 pages, 2371 KB

Open AccessArticle

Seasonal Changes in the Tetrodotoxin Content of the Flatworm Planocera multitentaculata

by Riko Yamada, Tadasuke Tsunashima, Mitsuki Takei, Tatsunori Sato, Yoshiki Wajima, Makoto Kawase, Shotaro Oshikiri, Yusuke Kajitani, Keita Kosoba, Hiroyuki Ueda, Koko Abe, Shiro Itoi and Haruo Sugita

Mar. Drugs 2017, 15(3), 56; https://doi.org/10.3390/md15030056 - 25 Feb 2017

Cited by 27 | Viewed by 8266

Abstract

Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera [...] Read more.

Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera multitentaculata is a known TTX-bearing organism, and is suspected to be a TTX supplier to pufferfish. In this study, flatworm specimens were collected from an intertidal zone in Hayama, Kanagawa, Japan, the TTX content of the flatworm was measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and seasonal changes in TTX content were investigated. No significant difference in TTX concentration of the flatworm body was found between the spawning period and other periods. However, the TTX content in individual flatworms was significantly higher in the spawning period than at other times. The TTX content rose in association with an increase in the body weight of the flatworm. Full article

(This article belongs to the Special Issue Marine Neurotoxins)

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12 pages, 3162 KB

Open AccessArticle

Tuberatolide B Suppresses Cancer Progression by Promoting ROS-Mediated Inhibition of STAT3 Signaling

by Youn Kyung Choi, Junseong Kim, Kang Min Lee, Yu-Jeong Choi, Bo-Ram Ye, Min-Sun Kim, Seong-Gyu Ko, Seung-Hong Lee, Do-Hyung Kang and Soo-Jin Heo

Mar. Drugs 2017, 15(3), 55; https://doi.org/10.3390/md15030055 - 25 Feb 2017

Cited by 37 | Viewed by 6915

Abstract

Tuberatolide B (TTB, C₂₇H₃₄O₄) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of TTB remain unknown. In this study, we demonstrate that TTB inhibits tumor growth in breast, [...] Read more.

Tuberatolide B (TTB, C₂₇H₃₄O₄) is a diastereomeric meroterpenoid isolated from the Korean marine algae Sargassum macrocarpum. However, the anticancer effects of TTB remain unknown. In this study, we demonstrate that TTB inhibits tumor growth in breast, lung, colon, prostate, and cervical cancer cells. To examine the mechanism by which TTB suppresses cell growth, we determined the effect of TTB on apoptosis, ROS generation, DNA damage, and signal transduction. TTB induced ROS production in MDA-MB-231, A549, and HCT116 cells. Moreover, TTB enhanced DNA damage by inducing γH2AX foci formation and the phosphorylation of DNA damage-related proteins such as Chk2 and H2AX. Furthermore, TTB selectively inhibited STAT3 activation, which resulted in a reduction in cyclin D1, MMP-9, survivin, VEGF, and IL-6. In addition, TTB-induced ROS generation caused STAT3 inhibition, DNA damage, and apoptotic cell death. Therefore, TTB suppresses cancer progression by promoting ROS-mediated inhibition of STAT3 signaling, suggesting that TTB is useful for the treatment of cancer. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology II 2016)

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