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Showing papers in "Marine Drugs in 2014"


Journal ArticleDOI
TL;DR: Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization.
Abstract: There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3'-dihydroxy-β, β'-carotene-4,4'-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications.

1,254 citations


Journal ArticleDOI
TL;DR: It is observed that chitosan modifies the morphology and size of these crystals, as well as changes the surface charge of the crystals, making them even more positive, which can facilitate the interaction ofThese crystals with renal cells.
Abstract: Chitosan is widely used in the biomedical field due its chemical and pharmacological properties. However, intake of chitosan results in renal tissue accumulation of chitosan and promotes an increase in calcium excretion. On the other hand, the effect of chitosan on the formation of calcium oxalate crystals (CaOx) has not been described. In this work, we evaluated the antioxidant capacity of chitosan and its interference in the formation of CaOx crystals in vitro. Here, the chitosan obtained commercially had its identity confirmed by nuclear magnetic resonance and infrared spectroscopy. In several tests, this chitosan showed low or no antioxidant activity. However, it also showed excellent copper-chelating activity. In vitro, chitosan acted as an inducer mainly of monohydrate CaOx crystal formation, which is more prevalent in patients with urolithiasis. We also observed that chitosan modifies the morphology and size of these crystals, as well as changes the surface charge of the crystals, making them even more positive, which can facilitate the interaction of these crystals with renal cells. Chitosan greatly influences the formation of crystals in vitro, and in vivo analyses should be conducted to assess the risk of using chitosan.

558 citations


Journal ArticleDOI
TL;DR: The paths of marine natural products discovery and development are outlined, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products.
Abstract: The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites are high-value commercial products for the pharmaceutical and cosmeceutical industries. The aim of this review is to outline the paths of marine natural products discovery and development, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products. The main challenges faced during marine bioactives discovery and development programs were analyzed and grouped in three categories: biodiversity (accessibility to marine resources and efficient screening), supply and technical (sustainable production of the bioactives and knowledge of the mechanism of action) and market (processes, costs, partnerships and marketing). Tips to surpass these challenges are given in order to improve the market entry success rates of highly promising marine bioactives in the current pipelines, highlighting what can be learned from the successful and unsuccessful stories that can be applied to novel and/or ongoing marine natural products discovery and development programs.

426 citations


Journal ArticleDOI
TL;DR: A comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010 is presented.
Abstract: Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overview of the source, taxonomy, country of origin or geographical position, chemical class, and biological activity of sponge-derived new natural products discovered between 2001 and 2010. The data has been analyzed with a view to gaining an outlook on the future trends and opportunities in the search for new compounds and their sources from marine sponges.

344 citations


Journal ArticleDOI
TL;DR: The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.
Abstract: Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.

277 citations


Journal ArticleDOI
TL;DR: This review highlights the power of co-cultivation for increasing the chemical diversity of bacteria and fungi drawing on published studies from the marine and from the terrestrial habitat alike.
Abstract: Marine-derived bacteria and fungi are promising sources of novel bioactive compounds that are important for drug discovery programs. However, as encountered in terrestrial microorganisms there is a high rate of redundancy that results in the frequent re-discovery of known compounds. Apparently only a part of the biosynthetic genes that are harbored by fungi and bacteria are transcribed under routine laboratory conditions which involve cultivation of axenic microbial strains. Many biosynthetic genes remain silent and are not expressed in vitro thereby seriously limiting the chemical diversity of microbial compounds that can be obtained through fermentation. In contrast to this, co-cultivation (also called mixed fermentation) of two or more different microorganisms tries to mimic the ecological situation where microorganisms always co-exist within complex microbial communities. The competition or antagonism experienced during co-cultivation is shown to lead to a significantly enhanced production of constitutively present compounds and/or to an accumulation of cryptic compounds that are not detected in axenic cultures of the producing strain. This review highlights the power of co-cultivation for increasing the chemical diversity of bacteria and fungi drawing on published studies from the marine and from the terrestrial habitat alike.

273 citations


Journal ArticleDOI
TL;DR: Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1) as discussed by the authors.
Abstract: Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1). They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated.

269 citations


Journal ArticleDOI
TL;DR: An overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer is provided and its robust biotechnological traits provide it with high potential to be a better organism than H. pluvialis for mass astrixanthin production.
Abstract: Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis possesses the highest intracellular astaxanthin content and is now believed to be a good producer of astaxanthin, it has intrinsic shortcomings such as slow growth rate, low biomass yield, and a high light requirement. In contrast, C. zofingiensis grows fast phototrophically, heterotrophically and mixtrophically, is easy to be cultured and scaled up both indoors and outdoors, and can achieve ultrahigh cell densities. These robust biotechnological traits provide C. zofingiensis with high potential to be a better organism than H. pluvialis for mass astaxanthin production. This review aims to provide an overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer. The path forward for further expansion of the astaxanthin production from C. zofingiensis with respect to both challenges and opportunities is also discussed.

236 citations


Journal ArticleDOI
TL;DR: This review shows the compounds derived from marine sources that are currently in clinical trials against cancer and the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.
Abstract: The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) as a warhead, have been approved for use in humans (Adcetris®). In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved), and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.

226 citations


Journal ArticleDOI
TL;DR: In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi
Abstract: Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each was characterized as a bone graft substitute. The porosity, water uptake and retention ability of the prepared scaffolds showed similar efficacy. The pore size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning electron microscopy and found to be 62-490 and 56-437 µm, respectively. In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a promising biomaterial for bone tissue regeneration.

201 citations


Journal ArticleDOI
TL;DR: The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits.
Abstract: Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits.

Journal ArticleDOI
TL;DR: The effects of systemic and local administration of fucoidan on tumor growth, angiogenesis, and immune reaction are discussed and whether in vivo and in vitro results are likely applicable to the development offucoidan as a marine anticancer drug are discussed.
Abstract: Fucoidan is a fucose-containing sulfated polysaccharide derived from brown seaweeds, crude extracts of which are commercially available as nutritional supplements. Recent studies have demonstrated antiproliferative, antiangiogenic, and anticancer properties of fucoidan in vitro. Accordingly, the anticancer effects of fucoidan have been shown to vary depending on its structure, while it can target multiple receptors or signaling molecules in various cell types, including tumor cells and immune cells. Low toxicity and the in vitro effects of fucoidan mentioned above make it a suitable agent for cancer prevention or treatment. However, preclinical development of natural marine products requires in vivo examination of purified compounds in animal tumor models. This review discusses the effects of systemic and local administration of fucoidan on tumor growth, angiogenesis, and immune reaction and whether in vivo and in vitro results are likely applicable to the development of fucoidan as a marine anticancer drug.

Journal ArticleDOI
TL;DR: Other emerging technologies such as direct degradation of chitin from crustacean shells and microbial cell walls, enzymatic synthesis of COS from small building blocks, and protein engineering technology for chit in-related enzymes have been discussed as the most significant challenge for industrial application.
Abstract: Chitin and chitosan oligosaccharides (COS) have been traditionally obtained by chemical digestion with strong acids. In light of the difficulties associated with these traditional production processes, environmentally compatible and reproducible production alternatives are desirable. Unlike chemical digestion, biodegradation of chitin and chitosan by enzymes or microorganisms does not require the use of toxic chemicals or excessive amounts of wastewater. Enzyme preparations with chitinase, chitosanase, and lysozymeare primarily used to hydrolyze chitin and chitosan. Commercial preparations of cellulase, protease, lipase, and pepsin provide another opportunity for oligosaccharide production. In addition to their hydrolytic activities, the transglycosylation activity of chitinolytic enzymes might be exploited for the synthesis of desired chitin oligomers and their derivatives. Chitin deacetylase is also potentially useful for the preparation of oligosaccharides. Recently, direct production of oligosaccharides from chitin and crab shells by a combination of mechanochemical grinding and enzymatic hydrolysis has been reported. Together with these, other emerging technologies such as direct degradation of chitin from crustacean shells and microbial cell walls, enzymatic synthesis of COS from small building blocks, and protein engineering technology for chitin-related enzymes have been discussed as the most significant challenge for industrial application.

Journal ArticleDOI
TL;DR: The microcystis CAWBG11 (which produces at least 27 congeners) was positioned in the top ten percentile of the strains surveyed, and showed fluidity of the amino acids incorporated into both position two and position four, as well as tandem mass spectrometry and chemical derivatization.
Abstract: Microcystins (MCs) are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Differences in the coding of the non‑ribosomal peptide synthetase/polyketide synthase enzyme complex responsible for microcystin production have resulted in more than 100 microcystin variants being reported to date. The microcystin diversity of Microcystis CAWBG11 was investigated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-mass spectrometry. This revealed that CAWBG11 simultaneously produced 21 known microcystins and six new congeners: [Asp3] MC-RA, [Asp3] MC-RAba, [Asp3] MC-FA, [Asp3] MC-WA, MC-FAba and MC-FL. The new congeners were putatively characterized by tandem mass spectrometry and chemical derivatization. A survey of the microcystin congeners produced by 49 cyanobacterial strains documented in scientific literature showed that cyanobacteria generally produce four microcystin congeners, but strains which produce up to 47 microcystin congeners have been reported. Microcystis CAWBG11 (which produces at least 27 congeners) was positioned in the top ten percentile of the strains surveyed, and showed fluidity of the amino acids incorporated into both position two and position four.

Journal ArticleDOI
TL;DR: This document covers most of the science regarding the holothurian FucCS, a structurally distinct glycosaminoglycan found in sea cucumber species that may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities.
Abstract: Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein.

Journal ArticleDOI
TL;DR: Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.
Abstract: Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

Journal ArticleDOI
TL;DR: Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.
Abstract: The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.

Journal ArticleDOI
TL;DR: This review is intended to serve as a practical guide to conotoxins superfamilies and to facilitate interpretation of the increasing number of conotoxin precursor sequences being identified by targeted-cDNA sequencing and more recently high-throughput transcriptome sequencing.
Abstract: Conotoxins are the peptidic components of the venoms of marine cone snails (genus Conus). They are remarkably diverse in terms of structure and function. Unique potency and selectivity profiles for a range of neuronal targets have made several conotoxins valuable as research tools, drug leads and even therapeutics, and has resulted in a concerted and increasing drive to identify and characterise new conotoxins. Conotoxins are translated from mRNA as peptide precursors, and cDNA sequencing is now the primary method for identification of new conotoxin sequences. As a result, gene superfamily, a classification based on precursor signal peptide identity, has become the most convenient method of conotoxin classification. Here we review each of the described conotoxin gene superfamilies, with a focus on the structural and functional diversity present in each. This review is intended to serve as a practical guide to conotoxin superfamilies and to facilitate interpretation of the increasing number of conotoxin precursor sequences being identified by targeted-cDNA sequencing and more recently high-throughput transcriptome sequencing.

Journal ArticleDOI
TL;DR: High resolution Fourier transform mass spectrometry and nuclear magnetic resonance spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp.
Abstract: High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.

Journal ArticleDOI
TL;DR: This review summarizes the current knowledge of cephalopod ink and discusses the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production.
Abstract: One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our current knowledge of cephalopod ink. Topics include: (1) the production of ink, including the functional organization of the ink sac and funnel organ that produce it; (2) the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production; (3) the neuroecology of the use of ink in predator-prey interactions by cephalopods in their natural environment; and (4) the use of cephalopod ink by humans, including in the development of drugs for biomedical applications and other chemicals for industrial and other commercial applications. As is hopefully evident from this review, much is known about cephalopod ink and inking, yet more striking is how little we know. Towards closing that gap, future directions in research on cephalopod inking are suggested.

Journal ArticleDOI
Dongbo Xu1, Wan-wan Ye1, Ying Han1, Zixin Deng1, Kui Hong1 
TL;DR: This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.
Abstract: Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery.

Journal ArticleDOI
TL;DR: An overview of the knowledge the authors have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data is given.
Abstract: Marine snails of the genus Conus are a large family of predatory gastropods with an unparalleled molecular diversity of pharmacologically active compounds in their venom. Cone snail venom comprises of a rich and diverse cocktail of peptide toxins which act on a wide variety of ion channels such as voltage-gated sodium- (NaV), potassium- (KV), and calcium- (CaV) channels as well as nicotinic acetylcholine receptors (nAChRs) which are classified as ligand-gated ion channels. The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure–function relationship data.

Journal ArticleDOI
TL;DR: It was demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes.
Abstract: Astaxanthin (ATX) has been proven to ameliorate early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH) by modulating cerebral oxidative stress This study was performed to assess the effect of ATX on the Nrf2-ARE pathway and to explore the underlying molecular mechanisms of antioxidant properties of ATX in EBI after SAH A total of 96 male SD rats were randomly divided into four groups Autologous blood was injected into the prechiasmatic cistern of the rat to induce an experimental SAH model Rats in each group were sacrificed at 24 h after SAH Expressions of Nrf2 and heme oxygenase-1 (HO-1) were measured by Western blot and immunohistochemistry analysis The mRNA levels of HO-1, NAD (P) H: quinone oxidoreductase 1 (NQO-1), and glutathione S-transferase-α1 (GST-α1) were determined by real-time polymerase chain reaction (PCR) It was observed that administration of ATX post-SAH could up-regulate the cortical expression of these agents, mediated in the Nrf2-ARE pathway at both pretranscriptional and posttranscriptional levels Meanwhile, oxidative damage was reduced Furthermore, ATX treatment significantly attenuated brain edema, blood–brain barrier (BBB) disruption, cellular apoptosis, and neurological dysfunction in SAH models This study demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes

Journal ArticleDOI
TL;DR: In marine microorganisms the produced EPS provide an instrument to survive in adverse conditions: They are found to envelope the cells by allowing the entrapment of nutrients or the adhesion to solid substrates.
Abstract: In the last decades, research has focused on the capabilities of microbes to secrete exopolysaccharides (EPS), because these polymers differ from the commercial ones derived essentially from plants or algae in their numerous valuable qualities. These biopolymers have emerged as new polymeric materials with novel and unique physical characteristics that have found extensive applications. In marine microorganisms the produced EPS provide an instrument to survive in adverse conditions: They are found to envelope the cells by allowing the entrapment of nutrients or the adhesion to solid substrates. Even if the processes of synthesis and release of exopolysaccharides request high-energy investments for the bacterium, these biopolymers permit resistance under extreme environmental conditions. Marine bacteria like Bacillus, Halomonas, Planococcus, Enterobacter, Alteromonas, Pseudoalteromonas, Vibrio, Rhodococcus, Zoogloea but also Archaea as Haloferax and Thermococcus are here described as EPS producers underlining biopolymer hyperproduction, related fermentation strategies including the effects of the chemical composition of the media, the physical parameters of the growth conditions and the genetic and predicted experimental design tools.

Journal ArticleDOI
TL;DR: The synthetic method presented shows an attractive and facile route for producing low-cost chitin/lignin biosorbents with high efficiency of nickel and cadmium adsorption and will have a significant impact on the problematic issue of the utilization of chitinous waste from the seafood industry and lignin by-products from the pulp and paper industry.
Abstract: Novel, functional materials based on chitin of marine origin and lignin were prepared. The synthesized materials were subjected to physicochemical, dispersive-morphological and electrokinetic analysis. The results confirm the effectiveness of the proposed method of synthesis of functional chitin/lignin materials. Mechanism of chitin modification by lignin is based on formation of hydrogen bonds between chitin and lignin. Additionally, the chitin/lignin materials were studied from the perspective of waste water treatment. The synthetic method presented in this work shows an attractive and facile route for producing low-cost chitin/lignin biosorbents with high efficiency of nickel and cadmium adsorption (88.0% and 98.4%, respectively). The discovery of this facile method of synthesis of functional chitin/lignin materials will also have a significant impact on the problematic issue of the utilization of chitinous waste from the seafood industry, as well as lignin by-products from the pulp and paper industry.

Journal ArticleDOI
TL;DR: An integrated approach using UHPLC-DAD-QTOFMS providing both accurate mass full-scan mass spectrometry (MS) and tandem high resolution MS (MS/HRMS) data led to the identification of four novel isomers of the known anticancer compound, asperphenamate.
Abstract: In drug discovery, reliable and fast dereplication of known compounds is essential for identification of novel bioactive compounds. Here, we show an integrated approach using ultra-high performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOFMS) providing both accurate mass full-scan mass spectrometry (MS) and tandem high resolution MS (MS/HRMS) data. The methodology was demonstrated on compounds from bioactive marine-derived strains of Aspergillus, Penicillium, and Emericellopsis, including small polyketides, non-ribosomal peptides, terpenes, and meroterpenoids. The MS/HRMS data were then searched against an in-house MS/HRMS library of ~1300 compounds for unambiguous identification. The full scan MS data was used for dereplication of compounds not in the MS/HRMS library, combined with ultraviolet/visual (UV/Vis) and MS/HRMS data for faster exclusion of database search results. This led to the identification of four novel isomers of the known anticancer compound, asperphenamate. Except for very low intensity peaks, no false negatives were found using the MS/HRMS approach, which proved to be robust against poor data quality caused by system overload or loss of lock-mass. Only for small polyketides, like patulin, were both retention time and UV/Vis spectra necessary for unambiguous identification. For the ophiobolin family with many structurally similar analogues partly co-eluting, the peaks could be assigned correctly by combining MS/HRMS data and m/z of the [M + Na]+ ions.

Journal ArticleDOI
TL;DR: This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases.
Abstract: Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases.

Journal ArticleDOI
TL;DR: The ability of compounds present in seaweeds to act against colorectal and breast cancers is considered, and the potential use of seaweeds as anticancer agents is highlighted.
Abstract: Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

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TL;DR: It has been found that the nano size enhances the performances of chitins and chitosans in all cases considered, with no exceptions.
Abstract: The present review article is intended to direct attention to the technological advances made in the 2010–2014 quinquennium for the isolation and manufacture of nanofibrillar chitin and chitosan. Otherwise called nanocrystals or whiskers, n-chitin and n-chitosan are obtained either by mechanical chitin disassembly and fibrillation optionally assisted by sonication, or by e-spinning of solutions of polysaccharides often accompanied by poly(ethylene oxide) or poly(caprolactone). The biomedical areas where n-chitin may find applications include hemostasis and wound healing, regeneration of tissues such as joints and bones, cell culture, antimicrobial agents, and dermal protection. The biomedical applications of n-chitosan include epithelial tissue regeneration, bone and dental tissue regeneration, as well as protection against bacteria, fungi and viruses. It has been found that the nano size enhances the performances of chitins and chitosans in all cases considered, with no exceptions. Biotechnological approaches will boost the applications of the said safe, eco-friendly and benign nanomaterials not only in these fields, but also for biosensors and in targeted drug delivery areas.

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TL;DR: This is the first report investigating the biological activities of microalgae-derived MAAs in human cells and it is shown that the mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH) assay.
Abstract: Certain photosynthetic marine organisms have evolved mechanisms to counteract UV-radiation by synthesizing UV-absorbing compounds, such as mycosporine-like amino acids (MAAs) In this study, MAAs were separated from the extracts of marine green alga Chlamydomonas hedleyi using HPLC and were identified as porphyra-334, shinorine, and mycosporine-glycine (mycosporine-Gly), based on their retention times and maximum absorption wavelengths Furthermore, their structures were confirmed by triple quadrupole MS/MS Their roles as UV-absorbing compounds were investigated in the human fibroblast cell line HaCaT by analyzing the expression levels of genes associated with antioxidant activity, inflammation, and skin aging in response to UV irradiation The mycosporine-Gly extract, but not the other MAAs, had strong antioxidant activity in the 2,2-diphenyl-1-picryhydrazyl (DPPH) assay Furthermore, treatment with mycosporine-Gly resulted in a significant decrease in COX-2 mRNA levels, which are typically increased in response to inflammation in the skin, in a concentration-dependent manner Additionally, in the presence of MAAs, the UV-suppressed genes, procollagen C proteinase enhancer (PCOLCE) and elastin, which are related to skin aging, had increased expression levels equal to those in UV-mock treated cells Interestingly, the increased expression of involucrin after UV exposure was suppressed by treatment with the MAAs mycosporine-Gly and shinorine, but not porphyra-334 This is the first report investigating the biological activities of microalgae-derived MAAs in human cells