Marine Drugs

12 pages, 4721 KiB

Open AccessArticle

Plocabulin Displays Strong Cytotoxic Activity in a Personalized Colon Cancer Patient-Derived 3D Organoid Assay

by Alba Costales-Carrera, Asunción Fernández-Barral, Pilar Bustamante-Madrid, Laura Guerra, Ramón Cantero, Antonio Barbáchano and Alberto Muñoz

Mar. Drugs 2019, 17(11), 648; https://doi.org/10.3390/md17110648 - 19 Nov 2019

Cited by 32 | Viewed by 4547

Abstract

Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids [...] Read more.

Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids derived from three colorectal cancer (CRC) patients to study the effect of plocabulin in a personalized assay system that ensures dose dependence and high reproducibility. The cytotoxicity of plocabulin was an order of magnitude higher than that of the active irinotecan derivative SN38 (7-ethyl-10-hydroxy-camptothecin) in tumor organoids at different passages. Moreover, plocabulin maintained its strong cytotoxic activity in wash-out experiments, in which a short pulse treatment of tumor organoids was as efficient as continuous treatment. Our data show that plocabulin has a very potent cytotoxic action in CRC patient-derived tumor organoids, supporting ongoing clinical trials with plocabulin and the use of organoid assays to provide personalized validation of antitumor drugs. Full article

(This article belongs to the Special Issue 3D Cell Culture Based on Marine Resources)

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12 pages, 1464 KiB

Open AccessArticle

Piltunines A–F from the Marine-Derived Fungus Penicillium piltunense KMM 4668

by Shamil Sh. Afiyatullov, Olesya I. Zhuravleva, Alexandr S. Antonov, Elena V. Leshchenko, Mikhail V. Pivkin, Yuliya V. Khudyakova, Vladimir A. Denisenko, Evgeny A. Pislyagin, Natalya Yu. Kim, Dmitrii V. Berdyshev, Gunhild von Amsberg and Sergey A. Dyshlovoy

Mar. Drugs 2019, 17(11), 647; https://doi.org/10.3390/md17110647 - 18 Nov 2019

Cited by 15 | Viewed by 4085

Abstract

Six new carotane sesquiterpenoids piltunines A–F (1–6) together with known compounds (7–9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1– [...] Read more.

Six new carotane sesquiterpenoids piltunines A–F (1–6) together with known compounds (7–9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1–7 were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined. Full article

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15 pages, 1238 KiB

Open AccessArticle

Evaluation of Antifouling Potential and Ecotoxicity of Secondary Metabolites Derived from Red Algae of the Genus Laurencia

by Maria Protopapa, Manto Kotsiri, Sofoklis Mouratidis, Vassilios Roussis, Efstathia Ioannou and Skarlatos G. Dedos

Mar. Drugs 2019, 17(11), 646; https://doi.org/10.3390/md17110646 - 16 Nov 2019

Cited by 16 | Viewed by 3354

Abstract

Red algae of the genus Laurencia are known to biosynthesize and secrete an immense variety of secondary metabolites possessing a spectrum of biological activities against bacteria, invertebrates and mammalian cell lines. Following a rigorous cross-species screening process, herein we report the antifouling potential [...] Read more.

Red algae of the genus Laurencia are known to biosynthesize and secrete an immense variety of secondary metabolites possessing a spectrum of biological activities against bacteria, invertebrates and mammalian cell lines. Following a rigorous cross-species screening process, herein we report the antifouling potential of 25 secondary metabolites derived from species of the genus Laurencia, as well as the thorough evaluation of the ecotoxicity of selected metabolites against non-target marine arthropods and vertebrate cell lines. A number of these secondary metabolites exhibited potent antifouling activity and performed well in all screening tests. Our results show that perforenol (9) possesses similar antifouling activity with that already described for bromosphaerol, which is used herein as a benchmark. Full article

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15 pages, 6319 KiB

Open AccessArticle

Chitosan Oligosaccharide Attenuates Nonalcoholic Fatty Liver Disease Induced by High Fat Diet through Reducing Lipid Accumulation, Inflammation and Oxidative Stress in C57BL/6 Mice

by Wenjing Tao, Wanjing Sun, Lujie Liu, Geng Wang, Zhiping Xiao, Xun Pei and Minqi Wang

Mar. Drugs 2019, 17(11), 645; https://doi.org/10.3390/md17110645 - 16 Nov 2019

Cited by 71 | Viewed by 4822

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease closely associated with metabolic syndrome, but there are no validated pharmacological therapies. The aim of this study was to investigate the effect of chitosan oligosaccharide (COS) on NAFLD. Mice were [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease closely associated with metabolic syndrome, but there are no validated pharmacological therapies. The aim of this study was to investigate the effect of chitosan oligosaccharide (COS) on NAFLD. Mice were fed either a control diet or a high-fat diet (HFD) with or without COS (200 or 400 mg/kg body weight (BW)) by oral gavage for seven weeks. Administration with COS significantly lowered serum lipid levels in the HFD-fed mice. The hepatic lipid accumulation was significantly decreased by COS, which was attributed to decreased expressions of lipogenic genes and increased expressions of fatty β-oxidation-related genes. Moreover, pro-inflammatory cytokines, neutrophils infiltration, and macrophage polarization were decreased by COS in the liver. Furthermore, COS ameliorated hepatic oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2) pathway and upregulating gene expressions of antioxidant enzymes. These beneficial effects were mediated by the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Therefore, COS might be a potent dietary supplement to ameliorate NAFLD. Full article

(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)

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12 pages, 1485 KiB

Open AccessFeature PaperArticle

Thuwalallenes A–E and Thuwalenynes A–C: New C₁₅ Acetogenins with Anti-Inflammatory Activity from a Saudi Arabian Red Sea Laurencia sp.

by Aikaterini Koutsaviti, Maria G. Daskalaki, Susana Agusti, Sotirios C. Kampranis, Christos Tsatsanis, Carlos M. Duarte, Vassilios Roussis and Efstathia Ioannou

Mar. Drugs 2019, 17(11), 644; https://doi.org/10.3390/md17110644 - 15 Nov 2019

Cited by 10 | Viewed by 3439

Abstract

Thuwalallenes A–E (1–3, 5 and 8) and thuwalenynes A–C (4, 6, 7), new C₁₅ acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol [...] Read more.

Thuwalallenes A–E (1–3, 5 and 8) and thuwalenynes A–C (4, 6, 7), new C₁₅ acetogenins featuring uncommon ring systems, along with cis-maneonene D (9), thyrsiferol (10) and 23-acetyl-thyrsiferol (11) were isolated from the organic extract of a population of the red alga Laurencia sp., collected at Rose Reef off the village of Thuwal in the Red Sea waters of the Kingdom of Saudi Arabia. The structure elucidation of the isolated natural products was based on extensive analysis of their spectroscopic data. Compounds 1–6, 8, 10 and 11 were evaluated for their anti-inflammatory activity by quantifying nitric oxide (NO) release in response to TLR4 stimulation in macrophages. Besides compound 4 that did not exhibit any activity, all other tested metabolites inhibited NO production from activated macrophages. Among them, thyrsiferol (10) and 23-acetylthyrsiferol (11) displayed activity with IC₅₀ values in the low nM scale without cytotoxicity. Full article

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22 pages, 2207 KiB

Open AccessArticle

Novel Microcystins from Planktothrix prolifica NIVA-CYA 544 Identified by LC-MS/MS, Functional Group Derivatization and ¹⁵N-labeling

by Vittoria Mallia, Silvio Uhlig, Cheryl Rafuse, Juris Meija and Christopher O. Miles

Mar. Drugs 2019, 17(11), 643; https://doi.org/10.3390/md17110643 - 15 Nov 2019

Cited by 21 | Viewed by 4795

Abstract

Microcystins are cyclic heptapeptides from cyanobacteria that are potent inhibitors of protein phosphatases and are toxic to animals and humans. At present, more than 250 microcystin variants are known, with variants reported for all seven peptide moieties. While d-glutamic acid (d [...] Read more.

Microcystins are cyclic heptapeptides from cyanobacteria that are potent inhibitors of protein phosphatases and are toxic to animals and humans. At present, more than 250 microcystin variants are known, with variants reported for all seven peptide moieties. While d-glutamic acid (d-Glu) is highly-conserved at position-6 of microcystins, there has been only one report of a cyanobacterium (Anabaena) producing microcystins containing l-Glu at the variable 2- and 4-positions. Liquid chromatography–mass spectrometry analyses of extracts from Planktothrix prolifica NIVA-CYA 544 led to the tentative identification of two new Glu-containing microcystins, [d-Asp³]MC-ER (12) and [d-Asp³]MC-EE (13). Structure determination was aided by thiol derivatization of the Mdha⁷-moiety and esterification of the carboxylic acid groups, while ¹⁵N-labeling of the culture and isotopic profile analysis assisted the determination of the number of nitrogen atoms present and the elemental composition of molecular and product-ions. The major microcystin analog in the extracts was [d-Asp³]MC-RR (1). A microcystin with an unprecedented high-molecular-mass (2116 Da) was also detected and tentatively identified as a sulfide-linked conjugate of [d-Asp³]MC-RR (15) by LC–HRMS/MS and sulfide oxidation, together with its sulfoxide (16) produced via autoxidation. Low levels of [d-Asp³]MC-RW (14), [d-Asp³]MC-LR (4), [d-Asp³,Mser⁷]MC-RR (11), [d-Asp³]MC-RY (17), [d-Asp³]MC-RF (18), [d-Asp³]MC-RR–glutathione conjugate (19), and [d-Asp³]MC-RCit (20), the first reported microcystin containing citrulline, were also identified in the extract, and an oxidized derivative of [d-Asp³]MC-RR and the cysteine conjugate of 1 were partially characterized. Full article

(This article belongs to the Special Issue New Challenges in Structure Elucidation of Marine Natural Products: NMR Analyses and Other Advanced Methods)

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13 pages, 2441 KiB

Open AccessArticle

Preparation of Antioxidant Peptide by Microwave- Assisted Hydrolysis of Collagen and Its Protective Effect Against H₂O₂-Induced Damage of RAW264.7 Cells

by Yan Li, Jie Li, Sai-Jun Lin, Zui-Su Yang and Huo-Xi Jin

Mar. Drugs 2019, 17(11), 642; https://doi.org/10.3390/md17110642 - 14 Nov 2019

Cited by 53 | Viewed by 4290

Abstract

Antioxidant peptides have elicited interest for the versatility of their use in the food and pharmaceutical industry. In the current study, antioxidant peptides were prepared by microwave-assisted alkaline protease hydrolysis of collagen from sea cucumber (Acaudina molpadioides). The results showed that [...] Read more.

Antioxidant peptides have elicited interest for the versatility of their use in the food and pharmaceutical industry. In the current study, antioxidant peptides were prepared by microwave-assisted alkaline protease hydrolysis of collagen from sea cucumber (Acaudina molpadioides). The results showed that microwave irradiation significantly improved the degree of hydrolysis of collagen and the hydroxyl radical (OH⋅) scavenging activity of hydrolysate. The content and OH⋅ scavenging activity of collagen peptides with molecular weight ≤ 1 kDa (CP_S) in the hydrolysate obtained at 250 W increased significantly compared with the non-microwave-assisted control. CP_S could scavenge OH⋅ and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical in a dose-dependent manner. The scavenging activity of OH⋅ and DPPH radical was 93.1% and 41.2%, respectively, at CP_S concentration of 1 mg/mL. CP_S could significantly promote RAW264.7 cell proliferation and reduce the Reactive Oxygen Species (ROS) level of H₂O₂-induced damage in RAW264.7 cells in a dose-dependent manner. Furthermore, all CP_S-treated groups exhibited an increase in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and a decrease in malondialdehyde (MDA) level compared with the control. These results showed that CP_S could effectively protect RAW264.7 cells from H₂O₂-induced damage, implying the potential utilization of CP_S as a natural antioxidant for food and pharmaceutical applications. Full article

(This article belongs to the Special Issue Active Compounds from Sea Cucumber)

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13 pages, 1312 KiB

Open AccessArticle

A Microbiological, Toxicological, and Biochemical Study of the Effects of Fucoxanthin, a Marine Carotenoid, on Mycobacterium tuberculosis and the Enzymes Implicated in Its Cell Wall: A Link Between Mycobacterial Infection and Autoimmune Diseases

by Miroslava Šudomová, Mohammad Ali Shariati, Javier Echeverría, Ioana Berindan-Neagoe, Seyed Mohammad Nabavi and Sherif T. S. Hassan

Mar. Drugs 2019, 17(11), 641; https://doi.org/10.3390/md17110641 - 14 Nov 2019

Cited by 18 | Viewed by 3963

Abstract

This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the [...] Read more.

This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the mechanism underlying the antitubercular effect of fucoxanthin. The obtained results showed that fucoxanthin showed a clear bacteriostatic action against the all Mtb strains tested, with minimum inhibitory concentrations (MIC) ranging from 2.8 to 4.1 µM, along with a good degree of selectivity index (ranging from 6.1 to 8.9) based on cellular toxicity evaluation compared with standard drug isoniazid (INH). The potent inhibitory actions of fucoxanthin and standard uridine-5’-diphosphate against UGM were recorded to be 98.2% and 99.2%, respectively. TBNAT was potently inactivated by fucoxanthin (half maximal inhibitory concentration (IC₅₀) = 4.8 µM; 99.1% inhibition) as compared to INH (IC₅₀ = 5.9 µM; 97.4% inhibition). Further, molecular docking approaches were achieved to endorse and rationalize the biological findings along with envisaging structure-activity relationships. Since the clinical evidence of the last decade has confirmed the correlation between bacterial infections and autoimmune diseases, in this study we have discussed the linkage between infection with Mtb and autoimmune diseases based on previous clinical observations and animal studies. In conclusion, we propose that fucoxanthin could demonstrate great therapeutic value for the treatment of tuberculosis by acting on multiple targets through a bacteriostatic effect as well as by inhibiting UGM and TBNAT. Such outcomes may lead to avoiding or decreasing the susceptibility to autoimmune diseases associated with Mtb infection in a genetically susceptible host. Full article

(This article belongs to the Special Issue Marine Natural Products and Autoimmune Diseases: From Chemistry and Molecular Mechanism to Clinical Efficacy)

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21 pages, 3244 KiB

Open AccessReview

Microalgal Carotenoids: A Review of Production, Current Markets, Regulations, and Future Direction

by Lucie Novoveská, Michael E. Ross, Michele S. Stanley, Rémi Pradelles, Virginie Wasiolek and Jean-François Sassi

Mar. Drugs 2019, 17(11), 640; https://doi.org/10.3390/md17110640 - 13 Nov 2019

Cited by 310 | Viewed by 17945

Abstract

Microalgae produce a variety of compounds that are beneficial to human and animal health. Among these compounds are carotenoids, which are microalgal pigments with unique antioxidant and coloring properties. The objective of this review is to evaluate the potential of using microalgae as [...] Read more.

Microalgae produce a variety of compounds that are beneficial to human and animal health. Among these compounds are carotenoids, which are microalgal pigments with unique antioxidant and coloring properties. The objective of this review is to evaluate the potential of using microalgae as a commercial feedstock for carotenoid production. While microalgae can produce some of the highest concentrations of carotenoids (especially astaxanthin) in living organisms, there are challenges associated with the mass production of microalgae and downstream processing of carotenoids. This review discusses the synthesis of carotenoids within microalgae, their physiological role, large-scale cultivation of microalgae, up- and down-stream processing, commercial applications, natural versus synthetic carotenoids, and opportunities and challenges facing the carotenoid markets. We emphasize legal aspects and regulatory challenges associated with the commercial production of microalgae-based carotenoids for food/feed, nutraceutical and cosmetic industry in Europe, the USA, the People’s Republic of China, and Japan. This review provides tools and a broad overview of the regulatory processes of carotenoid production from microalgae and other novel feedstocks. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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21 pages, 13940 KiB

Open AccessArticle

Deciphering Molecular Mechanism of the Neuropharmacological Action of Fucosterol through Integrated System Pharmacology and In Silico Analysis

by Md. Abdul Hannan, Raju Dash, Abdullah Al Mamun Sohag and Il Soo Moon

Mar. Drugs 2019, 17(11), 639; https://doi.org/10.3390/md17110639 - 13 Nov 2019

Cited by 31 | Viewed by 5869

Abstract

Fucosterol is an algae-derived unique phytosterol having several medicinal properties, including antioxidant, anti-inflammatory, anticholinesterase, neuroprotective, and so on. Accumulated evidence suggests a therapeutic promise of fucosterol in neurodegeneration; however, the in-depth pharmacological mechanism of its neuroprotection is poorly understood. Here, we employed system [...] Read more.

Fucosterol is an algae-derived unique phytosterol having several medicinal properties, including antioxidant, anti-inflammatory, anticholinesterase, neuroprotective, and so on. Accumulated evidence suggests a therapeutic promise of fucosterol in neurodegeneration; however, the in-depth pharmacological mechanism of its neuroprotection is poorly understood. Here, we employed system pharmacology and in silico analysis to elucidate the underlying mechanism of neuropharmacological action of fucosterol against neurodegenerative disorders (NDD). Network pharmacology revealed that fucosterol targets signaling molecules, receptors, enzymes, transporters, transcription factors, cytoskeletal, and various other proteins of cellular pathways, including tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), neurotrophin, and toll-like receptor (TLR) signaling, which are intimately associated with neuronal survival, immune response, and inflammation. Moreover, the molecular simulation study further verified that fucosterol exhibited a significant binding affinity to some of the vital targets, including liver X-receptor-beta (LXR-), glucocorticoid receptor (GR), tropomyosin receptor kinase B (TrkB), toll-like receptor 2/4 (TLR2/4), and

β

-secretase (BACE1), which are the crucial regulators of molecular and cellular processes associated with NDD. Together, the present system pharmacology and in silico findings demonstrate that fucosterol might play a significant role in modulating NDD-pathobiology, supporting its therapeutic application for the prevention and treatment of NDD. Full article

(This article belongs to the Special Issue Marine Organisms with Neuroprotective Activity: Molecular Targets and Action Mechanisms)

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17 pages, 1567 KiB

Open AccessReview

Mycosporine-Like Amino Acids: Making the Foundation for Organic Personalised Sunscreens

by Nedeljka N. Rosic

Mar. Drugs 2019, 17(11), 638; https://doi.org/10.3390/md17110638 - 12 Nov 2019

Cited by 82 | Viewed by 9311

Abstract

The surface of the Earth is exposed to harmful ultraviolet radiation (UVR: 280–400 nm). Prolonged skin exposure to UVR results in DNA damage through oxidative stress due to the production of reactive oxygen species (ROS). Mycosporine-like amino acids (MAAs) are UV-absorbing compounds, found [...] Read more.

The surface of the Earth is exposed to harmful ultraviolet radiation (UVR: 280–400 nm). Prolonged skin exposure to UVR results in DNA damage through oxidative stress due to the production of reactive oxygen species (ROS). Mycosporine-like amino acids (MAAs) are UV-absorbing compounds, found in many marine and freshwater organisms that have been of interest in use for skin protection. MAAs are involved in photoprotection from damaging UVR thanks to their ability to absorb light in both the UV-A (315–400 nm) and UV-B (280–315 nm) range without producing free radicals. In addition, by scavenging ROS, MAAs play an antioxidant role and suppress singlet oxygen-induced damage. Currently, there are over 30 different MAAs found in nature and they are characterised by different antioxidative and UV-absorbing capacities. Depending on the environmental conditions and UV level, up- or downregulation of genes from the MAA biosynthetic pathway results in seasonal fluctuation of the MAA content in aquatic species. This review will provide a summary of the MAA antioxidative and UV-absorbing features, including the genes involved in the MAA biosynthesis. Specifically, regulatory mechanisms involved in MAAs pathways will be evaluated for controlled MAA synthesis, advancing the potential use of MAAs in human skin protection. Full article

(This article belongs to the Special Issue Mycosporine-Like Amino Acids from Marine Resource)

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11 pages, 1576 KiB

Open AccessArticle

Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice

by Yuling Ding, Lei Wang, SeungTae Im, Ouibo Hwang, Hyun-Soo Kim, Min-Cheol Kang and Seung-Hong Lee

Mar. Drugs 2019, 17(11), 637; https://doi.org/10.3390/md17110637 - 10 Nov 2019

Cited by 26 | Viewed by 4284

Abstract

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current [...] Read more.

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases. Full article

(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)

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24 pages, 4094 KiB

Open AccessReview

A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000–2018

by Jianzhou Xu, Mengqi Yi, Lijian Ding and Shan He

Mar. Drugs 2019, 17(11), 636; https://doi.org/10.3390/md17110636 - 9 Nov 2019

Cited by 61 | Viewed by 6227

Abstract

Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more [...] Read more.

Inflammation is a generalized, nonspecific, and beneficial host response of foreign challenge or tissue injury. However, prolonged inflammation is undesirable. It will cause loss function of involve organs, such as heat, pain redness, and swelling. Marine natural products have gained more and more attention due to their unique mechanism of anti-inflammatory action, and have considered a hotspot for anti-inflammatory drug development. Marine-derived fungi are promising sources of structurally unprecedented bioactive natural products. So far, a plethora of new secondary metabolites with anti-inflammatory activities from marine-derived fungi had been widely reported. This review covers 133 fungal metabolites described in the period of 2000 to 2018, including the structures and origins of these secondary metabolites. Full article

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25 pages, 1408 KiB

Open AccessArticle

Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia

by Joko T. Wibowo, Matthias Y. Kellermann, Dennis Versluis, Masteria Y. Putra, Tutik Murniasih, Kathrin I. Mohr, Joachim Wink, Michael Engelmann, Dimas F. Praditya, Eike Steinmann and Peter J. Schupp

Mar. Drugs 2019, 17(11), 635; https://doi.org/10.3390/md17110635 - 8 Nov 2019

Cited by 18 | Viewed by 6300

Abstract

In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung [...] Read more.

In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS¹) as well as product/daughter ions (MS²) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential. Full article

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

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17 pages, 3177 KiB

Open AccessArticle

Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus Phyllospongia, with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine

by Seon Min Lee, Na-Hyun Kim, Sangbum Lee, Yun Na Kim, Jeong Doo Heo, Eun Ju Jeong and Jung-Rae Rho

Mar. Drugs 2019, 17(11), 634; https://doi.org/10.3390/md17110634 - 8 Nov 2019

Cited by 16 | Viewed by 3602

Abstract

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the [...] Read more.

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1β and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD. Full article

(This article belongs to the Special Issue Marine Immunomodulators)

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18 pages, 2102 KiB

Open AccessArticle

Quantitative Structure-Activity Relationship Model to Predict Antioxidant Effects of the Peptide Fraction Extracted from a Co-Culture System of Chlorella pyrenoidosa and Yarrowia lipolytica

by Huifan Liu, Sufen Li, Yuming Zhong, Jianliang Liu, Hui Liu, Jian Cheng, Lukai Ma, Yuqing Huang, Xuanyi Cai, Haijun Liu, Jiantong Zheng, Zhongai Su and Qin Wang

Mar. Drugs 2019, 17(11), 633; https://doi.org/10.3390/md17110633 - 8 Nov 2019

Cited by 7 | Viewed by 2767

Abstract

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed [...] Read more.

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC₅₀ value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R² > 0.9, Q² > 0.5). Thus, EHPs show potential as potent new antioxidant agents. Full article

(This article belongs to the Special Issue Strategies for Enhancing the Metabolome of Marine-Derived Fungi)

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14 pages, 1530 KiB

Open AccessArticle

Anti-Aging Effect of Agar Oligosaccharide on Male Drosophila melanogaster and Its Preliminary Mechanism

by Chao Ma, Kun Yang, Yifan Wang and Xianjun Dai

Mar. Drugs 2019, 17(11), 632; https://doi.org/10.3390/md17110632 - 6 Nov 2019

Cited by 25 | Viewed by 4499

Abstract

Agar oligosaccharide (AOS) is a marine prebiotic with apparent anti-inflammatory, antioxidant and anti-tumor effects. During this study, different doses of AOS are added to a basal diet to evaluate its effects on the lifespan, motor vigor and reproduction of male Drosophila melanogaster. [...] Read more.

Agar oligosaccharide (AOS) is a marine prebiotic with apparent anti-inflammatory, antioxidant and anti-tumor effects. During this study, different doses of AOS are added to a basal diet to evaluate its effects on the lifespan, motor vigor and reproduction of male Drosophila melanogaster. Additionally, the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase (CAT) and the malondialdehyde (MDA) content in male Drosophila are examined on the 10th, 25th and 40th days. The fly midguts are removed on the 10th and 40th days for analyses of the intestinal microbial community by 16S rDNA sequencing and the expression level of intestinal immunity genes by quantitative real-time PCR (RT-PCR). The results show that AOS significantly prolonged the average and maximum lifespan and increased the antioxidant capacity of male Drosophila. Additionally, AOS significantly regulated the structure of the intestinal flora of "old" flies (40 days) and upregulated the expression of immune deficiency (IMD) genes to improve the intestinal immunity, which could be beneficial for delaying aging in old flies. The above-described results provide a theoretical basis for the application of AOS, a type of marine oligosaccharide, as a nutritional supplement or immunomodulator. Full article

(This article belongs to the Special Issue Marine Antioxidant)

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27 pages, 744 KiB

Open AccessArticle

Structures and Bioactivities of Psolusosides B₁, B₂, J, K, L, M, N, O, P, and Q from the Sea Cucumber Psolus fabricii. The First Finding of Tetrasulfated Marine Low Molecular Weight Metabolites

by Alexandra S. Silchenko, Anatoly I. Kalinovsky, Sergey A. Avilov, Vladimir I. Kalinin, Pelageya V. Andrijaschenko, Pavel S. Dmitrenok, Roman S. Popov and Ekaterina A. Chingizova

Mar. Drugs 2019, 17(11), 631; https://doi.org/10.3390/md17110631 - 6 Nov 2019

Cited by 15 | Viewed by 2713

Abstract

Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B₁ (1), B₂ (2), J (3), K (4), L (5), M (6), N (7), O (8), [...] Read more.

Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B₁ (1), B₂ (2), J (3), K (4), L (5), M (6), N (7), O (8), P (9), and Q (10), were isolated from the sea cucumber Psolus fabricii collected in the Sea of Okhotsk near the Kurile Islands. Structures of these glycosides were established by two-dimensional (2D) NMR spectroscopy and HR-ESI mass-spectrometry. It is particularly interesting that highly polar compounds 9 and 10 contain four sulfate groups in their carbohydrate moieties, including two sulfates in the same terminal glucose residue. Glycoside 2 has an unusual non-holostane aglycone with 18(16)-lactone and a unique 7,8-epoxy fragment. Cytotoxic activities of compounds 1–10 against several mouse cell lines such as Ehrlich ascites carcinoma cells, neuroblastoma Neuro 2A, normal epithelial JB-6 cells, and erythrocytes were quite different depending both on structural peculiarities of these glycosides and the type of cells subjected to their actions. Psolusoside L (5), pentaoside, with three sulfate groups at C-6 of two glucose and one 3-O-methylglucose residue and holostane aglycone, is the most active compound in the series. The presence of a sulfate group at C-2 of the terminal glucose residue attached to C-4 of the first (xylose) residue significantly decreases activities of the corresponding glycosides. Psolusosides of group B (1, 2, and known psolusoside B) are inactive in all tests due to the presence of non-holostane aglycones and tetrasaccharide-branched sugar chains sulfated by C-2 of Glc4. Full article

(This article belongs to the Special Issue Marine Glycoconjugates: Trends and Perspectives)

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21 pages, 769 KiB

Open AccessFeature PaperArticle

Variation in Lipid Components from 15 Species of Tropical and Temperate Seaweeds

by Eko Susanto, A. Suhaeli Fahmi, Masashi Hosokawa and Kazuo Miyashita

Mar. Drugs 2019, 17(11), 630; https://doi.org/10.3390/md17110630 - 6 Nov 2019

Cited by 35 | Viewed by 4902

Abstract

The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated [...] Read more.

The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated fatty acids (PUFAs), and alpha tocopherol (α-Toc). Chlorophyll (Chl) and carotenoid contents varied among phyla, but not with the sampling location. Chl a and b were the major chlorophylls in Chlorophyta. Chl a and Chl c were the main chlorophylls in Ochrophyta, while Chl a was the dominant chlorophylls in Rhodophyta. β-Carotene and fucoxanthin were detected as major seaweed carotenoids. The former was present in all species in a variety of ranges, while the latter was mainly found in Ochrophyta and in small quantities in Rhodophyta, but not in Chlorophyta. The total lipids (TL) content and fatty acids composition were strongly affected by sampling location. The TL and n-3 PUFAs levels tended to be higher in temperate seaweeds compared with those in tropical seaweeds. The major n-3 PUFAs in different phyla, namely, eicosapentaenoic acid (EPA) and stearidonic acid (SDA) in Ochrophyta, α-linolenic acid (ALA) and SDA in Chlorophyta, and EPA in Rhodophyta, accumulated in temperate seaweeds. Chlorophylls, their derivatives, and carotenoids are known to have health benefits, such as antioxidant activities, while n-3 PUFAs are known to be essential nutrients that positively influence human nutrition and health. Therefore, seaweed lipids could be used as a source of ingredients with health benefits for functional foods and nutraceuticals. Full article

(This article belongs to the Special Issue Characterization of Bioactive Components in Edible Algae)

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17 pages, 5877 KiB

Open AccessArticle

Unique Aggregation of Sterigmatocystin in Water Yields Strong and Specific Circular Dichroism Response Allowing Highly Sensitive and Selective Monitoring of Bio-Relevant Interactions

by Daniela Jakšić, Maja Šegvić Klarić, Ivo Crnolatac, Nataša Šijaković Vujičić, Vilko Smrečki, Marcin Górecki, Gennaro Pescitelli and Ivo Piantanida

Mar. Drugs 2019, 17(11), 629; https://doi.org/10.3390/md17110629 - 6 Nov 2019

Cited by 6 | Viewed by 3443

Abstract

We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results [...] Read more.

We demonstrated the hitherto unknown property of the mycotoxin sterigmatocystin (STC) to provide homogeneous solutions in aqueous medium by forming a unique aggregate type (not formed by analogous aflatoxins), characterized by exceptionally strong circular dichroism (CD) bands in the 300–400 nm range. Results showed that these CD bands do not originate from intrinsic STC chirality but are a specific property of a peculiar aggregation process similar to psi-DNA CD response. Transmission electron microscopy (TEM) experiments revealed a fine fiber network resembling a supramolecular gel structure with helical fibers. Thermodynamic studies of aggregates by differential scanning calorimetry (DSC) revealed high reversibility of the dominant aggregation process. We demonstrated that the novel STC psi-CD band at 345 nm could be applied at biorelevant conditions (100 nanomolar concentration) and even in marine-salt content conditions for specific and quantitative monitoring of STC. Also, we showed that STC strongly non-covalently interacts with ds-DNA with likely toxic effects, thus contrary to the previous belief requiring prior enzyme epoxidation. Full article

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15 pages, 5146 KiB

Open AccessArticle

Effects of Astaxanthin from Shrimp Shell on Oxidative Stress and Behavior in Animal Model of Alzheimer’s Disease

by Takunrat Taksima, Pennapa Chonpathompikunlert, Morakot Sroyraya, Pilaiwanwadee Hutamekalin, Maruj Limpawattana and Wanwimol Klaypradit

Mar. Drugs 2019, 17(11), 628; https://doi.org/10.3390/md17110628 - 4 Nov 2019

Cited by 41 | Viewed by 5615

Abstract

This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) [...] Read more.

This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) Control, (2) sham operate, (3) negative control (vehicle) + Aβ_1-42, (4) ASX extract+Aβ_1-42, (5) commercial ASX + Aβ_1-42, (6) ASX powder + Aβ_1-42, (7) blank powder + Aβ_1-42, and (8) vitamin E + Aβ_1-42. All treatments were orally administrated for 30 days. At 14- and 29-days post injection, animals were observed in behavioral tests. On the 31st day, animals were sacrificed; the hippocampus and cortex were collected. Those two brain areas were then homogenized and stored for biochemical and histological analysis. The results showed that the Aβ_1-42 infused group significantly reduced cognitive ability and increased memory loss, as assessed by the Morris water maze test, novel object recognition test, and novel object location test. Moreover, the Aβ_1-42 infused group exhibited a deterioration of oxidative markers, including glutathione peroxidase enzymes (GPx), lipid peroxidation (MDA), products of protein oxidation, and superoxide anion in the cortex and the hippocampus. Meanwhile, ASX powder (10 mg/kg body weight) showed a significant reduction in cognitive and memory impairments and oxidative stress which is greater than ASX extract in the same dose of compound or vitamin E (100 mg/kg body weight). Our study indicates the beneficial properties of ASX in alleviation of cognitive functions and reducing neurodegeneration in Wistar rats induced by amyloid-β (1-42) peptides. Full article

(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)

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16 pages, 2180 KiB

Open AccessArticle

Development and Characterization of Astaxanthin-Containing Whey Protein-Based Nanoparticles

by Francesca Zanoni, Martina Vakarelova and Gianni Zoccatelli

Mar. Drugs 2019, 17(11), 627; https://doi.org/10.3390/md17110627 - 4 Nov 2019

Cited by 31 | Viewed by 4781

Abstract

Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The [...] Read more.

Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The aim of this work was to develop a method to stabilize astaxanthin extracted from the microalgae Haematococcus pluvialis (H.p.) and to improve its nutritional and functional properties through nanoencapsulation. Nanoparticles (NPs) were produced by emulsification–solvent evaporation technique starting from H.p. oleoresin using whey proteins concentrate (WPC) as stabilizer. The efficiency of encapsulation was 96%. The particle size (Z-average) was in the range of 80–130 nm and the superficial charge (measured as zeta-potential) was negative (−20 to −30 mV). The stability of the NPs upon resuspension in water was assayed through a panel of stress tests, i.e., extreme pH, UV radiation, Fe³⁺ exposition, and heating at 65 °C, that always showed a superior performance of encapsulated ASX in comparison to oleoresin, even if NPs tended to precipitate at pH 3.5–5.5. Simulated gastroenteric digestion was conducted to study the release of ASX in physiological conditions, and showed a maximum bioaccessibility of 76%, with 75% ASX converted into the more bioavailable free form. The collected data suggest that NPs might have possible future applications as supplements for human and animal diets. Full article

(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)

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12 pages, 1899 KiB

Open AccessArticle

Effect of Carboxymethylation and Phosphorylation on the Properties of Polysaccharides from Sepia esculenta Ink: Antioxidation and Anticoagulation in Vitro

by Huazhong Liu, Fangping Li and Ping Luo

Mar. Drugs 2019, 17(11), 626; https://doi.org/10.3390/md17110626 - 1 Nov 2019

Cited by 29 | Viewed by 3107

Abstract

To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of [...] Read more.

To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of an orthogonal experiment. The in vitro antioxidant and anticoagulant activities of the derivatives were determined by assessing the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals, which activated the partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results showed that SIP was modified successfully to be CSIP and PSIP, and degrees of substitution (DSs) of the two products were 0.9913 and 0.0828, respectively. Phosphorylation efficiently improved the antioxidant property of SIP, and the IC₅₀ values of PSIP on DPPH and hydroxyl radicals decreased by 63.25% and 13.77%, respectively. But carboxymethylation reduced antioxidant activity of the native polysaccharide, IC₅₀ values of CSIP on the DPPH and hydroxyl radicals increased by 16.74% and 6.89%, respectively. SIP significantly prolonged the APTT, PT, and TT in a dose-dependent fashion, suggesting that SIP played an anticoagulant action through intrinsic, extrinsic, and common coagulation pathways. CSIP and PSIP both possessed a stronger anticoagulant capacity than SIP via the same pathways; moreover, CSIP was observed to be more effective in prolonging APTT and PT than PSIP. Full article

(This article belongs to the Collection Marine Polysaccharides)

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16 pages, 4747 KiB

Open AccessArticle

Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells

by Marco Miceli, Adele Cutignano, Mariarosaria Conte, Raffaella Ummarino, Alessandra Romanelli, Menotti Ruvo, Marilisa Leone, Flavia Anna Mercurio, Nunzianna Doti, Emiliano Manzo, Giovanna Romano, Lucia Altucci and Adrianna Ianora

Mar. Drugs 2019, 17(11), 625; https://doi.org/10.3390/md17110625 - 1 Nov 2019

Cited by 22 | Viewed by 4197

Abstract

Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the [...] Read more.

Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells. Full article

(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)

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14 pages, 2785 KiB

Open AccessArticle

Computational Tools in the Discovery of FABP4 Ligands: A Statistical and Molecular Modeling Approach

by Giuseppe Floresta, Davide Gentile, Giancarlo Perrini, Vincenzo Patamia and Antonio Rescifina

Mar. Drugs 2019, 17(11), 624; https://doi.org/10.3390/md17110624 - 31 Oct 2019

Cited by 19 | Viewed by 4557

Abstract

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, [...] Read more.

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have received interest following the recent publication of their pharmacologically beneficial effects. Recently, it was revealed that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered, but, unfortunately, none have reached the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches have been used for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. We retrieved 14,492 compounds from this database and filtered through them with a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 97–331 nM. ADMET property prediction was performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives. From these analyses, three molecules that are excellent candidates for becoming new drugs were found. Full article

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13 pages, 3532 KiB

Open AccessArticle

Sediment as a Potential Pool for Lipophilic Marine Phycotoxins with the Case Study of Daya Bay of China

by Yang Liu, Peng Zhang, Sen Du, Zhuoru Lin, Yanyan Zhou, Lizhao Chen, Rencheng Yu and Li Zhang

Mar. Drugs 2019, 17(11), 623; https://doi.org/10.3390/md17110623 - 31 Oct 2019

Cited by 13 | Viewed by 2626

Abstract

Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment; however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of [...] Read more.

Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment; however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of LMPs in sediment, surface sediment samples collected from a tropical area of Daya Bay (DYB) at different seasons, were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). According to the results, up to six toxin compounds were detected in sediment samples from DYB, OA and DTX1 had the highest levels, followed by PTX2, homo-YTX, AZA2, and GYM. Although AZA2 and GYM were found in most of the sediment, OA, DTX1, homo-YTX, and PTX2 were the predominant toxin compounds, and PTX2 was the most ubiquitous toxin in sediment. The spatial distribution of LMP components in the sediment fluctuated with sampling times, partially according to the physical–chemical parameters of the sediment. There are likely several sources for LMPs existing in surface sediments, but it is difficult to determine contributions of a specific toxin-source in the sediment. Therefore, marine sediments may be a toxin reservoir for LMPs accumulation in benthic organisms via food chains. Full article

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10 pages, 2299 KiB

Open AccessArticle

Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells

by Su-Jeong Oh, Yoojin Seo, Ji-Su Ahn, Ye Young Shin, Ji Won Yang, Hyoung Kyu Kim, Jin Han, Natalia P. Mishchenko, Sergey A. Fedoreyev, Valentin A. Stonik and Hyung-Sik Kim

Mar. Drugs 2019, 17(11), 622; https://doi.org/10.3390/md17110622 - 31 Oct 2019

Cited by 25 | Viewed by 3855

Abstract

Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called ‘histochrome’. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and [...] Read more.

Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called ‘histochrome’. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and ocular degenerative disorders in Russia and its protective role has been studied for other pathologic conditions. In the present study, we sought to investigate the therapeutic potential of Ech A for inflammatory bowel disease (IBD) using a murine model of experimental colitis. We found that intravenous injection of Ech A significantly prevented body weight loss and subsequent lethality in colitis-induced mice. Interestingly, T cell proliferation was significantly inhibited upon Ech A treatment in vitro. During the helper T (Th) cell differentiation process, Ech A stimulated the generation regulatory T (Treg) cells that modulate the inflammatory response and immune homeostasis. Moreover, Ech A treatment suppressed the in vitro activation of pro-inflammatory M1 type macrophages, while inducing the production of M2 type macrophages that promote the resolution of inflammation and initiate tissue repair. Based on these results, we suggest that Ech A could provide a beneficial impact on IBD by correcting the imbalance in the intestinal immune system. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd International Symposium on Life Science)

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12 pages, 1619 KiB

Open AccessArticle

Improved Astaxanthin Production with Corynebacterium glutamicum by Application of a Membrane Fusion Protein

by Nadja A. Henke and Volker F. Wendisch

Mar. Drugs 2019, 17(11), 621; https://doi.org/10.3390/md17110621 - 31 Oct 2019

Cited by 41 | Viewed by 5444

Abstract

Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in [...] Read more.

Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in human nutrition. Natural astaxanthin is on the rise and, hence, alternative production systems are needed. The natural carotenoid producer Corynebacterium glutamicum is a potent host for industrial fermentations, such as million-ton scale amino acid production. In C. glutamicum, astaxanthin production was established through heterologous overproduction of the cytosolic lycopene cyclase CrtY and the membrane-bound β-carotene hydroxylase and ketolase, CrtZ and CrtW, in previous studies. In this work, further metabolic engineering strategies revealed that the potential of this GRAS organism for astaxanthin production is not fully exploited yet. It was shown that the construction of a fusion protein comprising the membrane-bound β-carotene hydroxylase and ketolase (CrtZ~W) significantly increased astaxanthin production under high glucose concentration. An evaluation of used carbon sources indicated that a combination of glucose and acetate facilitated astaxanthin production. Moreover, additional overproduction of cytosolic carotenogenic enzymes increased the production of this high value compound. Taken together, a seven-fold improvement of astaxanthin production was achieved with 3.1 mg/g CDW of astaxanthin. Full article

(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)

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18 pages, 3111 KiB

Open AccessReview

Successful Approaches for a Red Seaweed Biorefinery

by Milena Álvarez-Viñas, Noelia Flórez-Fernández, M. Dolores Torres and Herminia Domínguez

Mar. Drugs 2019, 17(11), 620; https://doi.org/10.3390/md17110620 - 30 Oct 2019

Cited by 69 | Viewed by 7327

Abstract

Macroalgae have been commercially exploited as food and for the production of phycocolloids, but they also contain compounds with potential in pharmaceutical, nutraceutical, cosmetic, chemical and energetic applications. The biorefinery concept applied to seaweed facilitates the extraction of different constituents ensuring full utilization [...] Read more.

Macroalgae have been commercially exploited as food and for the production of phycocolloids, but they also contain compounds with potential in pharmaceutical, nutraceutical, cosmetic, chemical and energetic applications. The biorefinery concept applied to seaweed facilitates the extraction of different constituents ensuring full utilization of resources and generating few residues through a succession of steps. Seaweed biorefineries are less advanced than those based on terrestrial biomass and the design of efficient processes requires further study. This review presents practical successful examples to obtain two or more commercially valuable components from red seaweeds. The selected processes consist on cascading stages of both conventional and alternative techniques to illustrate different possible valorization strategies. Full article

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15 pages, 2313 KiB

Open AccessArticle

Lemnalol Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes

by Buh-Yuan Tai, Zhi-Hong Wen, Pao-Yun Cheng, Hsiang-Yu Yang, Chang-Yih Duh, Ping-Nan Chen and Chih-Hsueng Hsu

Mar. Drugs 2019, 17(11), 619; https://doi.org/10.3390/md17110619 - 30 Oct 2019

Cited by 5 | Viewed by 3068

Abstract

Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic [...] Read more.

Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction and finally death. LPS challenge-induced inflammatory responses during sepsis may increase the likelihood of the arrhythmogenesis. Lemnalol is known to possess potent anti-inflammatory effects. This study examined whether Lemnalol (0.1 μM) could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes under the influence of LPS (1μg/mL). Under challenge with LPS, Lemnalol-treated LA myocytes, had a longer AP duration at 20%, 50% and 90% repolarization of the amplitude, compared to the LPS-treated cells. LPS-challenged LA myocytes showed increased late sodium current, Na⁺-Ca²⁺ exchanger current, transient outward current, rapid component of delayed rectifier potassium current, tumor necrosis factor-α, NF-κB and increased phosphorylation of ryanodine receptor (RyR), but a lower L-type Ca²⁺ current than the control LA myocytes. Exposure to Lemnalol reversed the LPS-induced effects. The LPS-treated and control groups of LA myocytes, with or without the existence of Lemnalol. showed no apparent alterations in the sodium current amplitude or Cav1.2 expression. The expression of sarcoendoplasmic reticulum calcium transport ATPase (SERCA2) was reduced by LPS treatment, while Lemnalol ameliorated the LPS-induced alterations. The phosphorylation of RyR was enhanced by LPS treatment, while Lemnalol attenuated the LPS-induced alterations. In conclusion, Lemnalol modulates LPS-induced alterations of LA calcium homeostasis and blocks the NF-κB pathways, which may contribute to the attenuation of LPS-induced arrhythmogenesis. Full article

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