Open AccessArticle
Cyanobacteria as Nanogold Factories: Chemical and Anti-Myocardial Infarction Properties of Gold Nanoparticles Synthesized by Lyngbya majuscula
Mar. Drugs 2018, 16(6), 217; https://doi.org/10.3390/md16060217 (registering DOI) -
Abstract
To the best of our knowledge, cyanobacterial strains from the Arabian Gulf have never been investigated with respect to their potential for nanoparticle production. Lyngbya majuscula was isolated from the AlOqair area, Al-Ahsa Government, Eastern Province, Kingdom of Saudi Arabia. The cyanobacterium was
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To the best of our knowledge, cyanobacterial strains from the Arabian Gulf have never been investigated with respect to their potential for nanoparticle production. Lyngbya majuscula was isolated from the AlOqair area, Al-Ahsa Government, Eastern Province, Kingdom of Saudi Arabia. The cyanobacterium was initially incubated with 1500 mg/mL of HAuCl4 for two days. The blue-green strain turned purple, which indicated the intracellular formation of gold nanoparticles. Prolonged incubation for over two months triggered the extracellular production of nanogold particles. UV-visible spectroscopy measurements indicated the presence of a resonance plasmon band at ~535 nm, whereas electron microscopy scanning indicated the presence of gold nanoparticles with an average diameter of 41.7 ± 0.2 nm. The antioxidant and anti-myocardial infarction activities of the cyanobacterial extract, the gold nanoparticle solution, and a combination of both were investigated in animal models. Isoproterenol (100 mg/kg, SC (sub cutaneous)) was injected into experimental rats for three days to induce a state of myocardial infarction; then the animals were given cyanobacterial extract (200 mg/kg/day, IP (intra peritoneal)), gold nanoparticles (200 mg/kg/day, IP), ora mixture of both for 14 days. Cardiac biomarkers, electrocardiogram (ECG), blood pressure, and antioxidant enzymes were determined as indicators of myocardial infarction. The results showed that isoproterenol elevates ST and QT segments and increases heart rate and serum activities of creatine phosphokinase (CPK), creatine kinase-myocardial bound (CP-MB), and cardiac troponin T (cTnT). It also reduces heart tissue content of glutathione peroxidase (GRx) and superoxide dismutase (SOD), and the arterial pressure indices of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP). Gold nanoparticles alone or in combination with cyanobacterial extract produced an inhibitory effect on isoproterenol-induced changes in serum cardiac injury markers, ECG, arterial pressure indices, and antioxidant capabilities of the heart. Full article
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Open AccessArticle
Dietary Supplementation with a Magnesium-Rich Marine Mineral Blend Enhances the Diversity of Gastrointestinal Microbiota
Mar. Drugs 2018, 16(6), 216; https://doi.org/10.3390/md16060216 (registering DOI) -
Abstract
Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar “Western
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Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar “Western diet” have been associated with health problems such as obesity, inflammatory bowel diseases, and cardiovascular diseases, as well as metabolic, immune, and psychiatric disorders. It is now recognized that modulating the diversity of gut microbiota, the population of intestinal bacteria, through dietary intervention can significantly impact upon gut health as well as systemic and brain health. In the current study, we show that supplementation with a seaweed and seawater-derived functional food ingredient rich in bioactive calcium and magnesium (0.1% supplementation) as well as 70 other trace elements, significantly enhanced the gut microbial diversity in adult male rats. Given the significant impact of gut microbiota on health, these results position this marine multi-mineral blend (MMB) as a promising digestive-health promoting functional food ingredient. Full article
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Open AccessArticle
Effect of Methionine Oxidation and Substitution of α-Conotoxin TxID on α3β4 Nicotinic Acetylcholine Receptor
Mar. Drugs 2018, 16(6), 215; https://doi.org/10.3390/md16060215 (registering DOI) -
Abstract
α-Conotoxin TxID was discovered from Conus textile by gene cloning, which has 4/6 inter-cysteine loop spacing and selectively inhibits α3β4 nicotinic acetylcholine receptor (nAChR) subtype. However, TxID is susceptible to modification due to it containing a methionine (Met) residue that easily forms methionine
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α-Conotoxin TxID was discovered from Conus textile by gene cloning, which has 4/6 inter-cysteine loop spacing and selectively inhibits α3β4 nicotinic acetylcholine receptor (nAChR) subtype. However, TxID is susceptible to modification due to it containing a methionine (Met) residue that easily forms methionine sulfoxide (MetO) in oxidative environment. In this study, we investigated how Met-11 and its derivatives affect the activity of TxID using a combination of electrophysiological recordings and molecular modelling. The results showed most TxID analogues had substantially decreased activities on α3β4 nAChR with more than 10-fold potency loss and 5 of them demonstrated no inhibition on α3β4 nAChR. However, one mutant, [M11I]TxID, displayed potent inhibition at α3β4 nAChR with an IC50 of 69 nM, which only exhibited 3.8-fold less compared with TxID. Molecular dynamics simulations were performed to expound the decrease in the affinity for α3β4 nAChR. The results indicate replacement of Met with a hydrophobic moderate-sized Ile in TxID is an alternative strategy to reduce the impact of Met oxidation, which may help to redesign conotoxins containing methionine residue. Full article
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Open AccessReview
Chemistry and Biological Activities of the Marine Sponges of the Genera Mycale (Arenochalina), Biemna and Clathria
Mar. Drugs 2018, 16(6), 214; https://doi.org/10.3390/md16060214 -
Abstract
Over the past seven decades, particularly since the discovery of the first marine-derived nucleosides, spongothymidine and spongouridine, from the Caribbean sponge Cryptotethya crypta in the early 1950s, marine natural products have emerged as unique, renewable and yet under-investigated pools for discovery of new
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Over the past seven decades, particularly since the discovery of the first marine-derived nucleosides, spongothymidine and spongouridine, from the Caribbean sponge Cryptotethya crypta in the early 1950s, marine natural products have emerged as unique, renewable and yet under-investigated pools for discovery of new drug leads with distinct structural features, and myriad interesting biological activities. Marine sponges are the most primitive and simplest multicellular animals, with approximately 8900 known described species, although more than 15,000 species are thought to exist worldwide today. These marine organisms potentially represent the richest pipeline for novel drug leads. Mycale (Arenochalina) and Clathria are recognized marine sponge genera belonging to the order Poecilosclerida, whereas Biemna was more recently reclassified, based on molecular genetics, as a new order Biemnida. Together, these sponge genera contribute to the production of physiologically active molecular entities with diverse structural features and a wide range of medicinal and therapeutic potentialities. In this review, we provide a comprehensive insight and up-to-date literature survey over the period of 1976–2018, focusing on the chemistry of the isolated compounds from members of these three genera, as well as their biological and pharmacological activities, whenever available. Full article
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Open AccessArticle
Raistrickiones A−E from a Highly Productive Strain of Penicillium raistrickii Generated through Thermo Change
Mar. Drugs 2018, 16(6), 213; https://doi.org/10.3390/md16060213 -
Abstract
Three new diastereomers of polyketides (PKs), raistrickiones A−C (13), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an
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Three new diastereomers of polyketides (PKs), raistrickiones A−C (13), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 15 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 15 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 15 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH). Full article
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Open AccessArticle
Breaking down Leukemia Walls: Heteronemin, a Sesterterpene Derivative, Induces Apoptosis in Leukemia Molt4 Cells through Oxidative Stress, Mitochondrial Dysfunction and Induction of Talin Expression
Mar. Drugs 2018, 16(6), 212; https://doi.org/10.3390/md16060212 -
Abstract
Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine
[...] Read more.
Heteronemin, the most abundant secondary metabolite in the sponge Hippospongia sp., exhibited potent cytotoxic activity against several cancer cell lines. It increased the percentage of apoptotic cells and reactive oxygen species (ROS) in Molt4 cells. The use of ROS scavenger, N-acetyl cysteine (NAC), suppressed both the production of ROS from mitochondria and cell apoptosis that were induced by heteronemin treatment. Heteronemin upregulated talin and phosphorylated talin expression in Molt4 cells but it only upregulated the expression of phosphorylated talin in HEK293 cells. However, pretreatment with NAC reversed these effects. Talin siRNA reversed the activation of pro-apoptotic cleaved caspases 3 and 9. On the other hand, the downstream proteins including FAK and NF-κB (p65) were not affected. In addition, we confirmed that heteronemin directly modulated phosphorylated talin expression through ROS generation resulting in cell apoptosis, but it did not affect talin/FAK complex. Furthermore, heteronemin interfered with actin microfilament and caused morphology changes. Taken together, these findings suggest that the cytotoxic effect of heteronemin is associated with oxidative stress and induction of phosphorylated talin expression. Our results suggest that heteronemin represents an interesting candidate which can be further developed as a drug lead against leukemia. Full article
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Open AccessArticle
Collagen from Cartilaginous Fish By-Products for a Potential Application in Bioactive Film Composite
Mar. Drugs 2018, 16(6), 211; https://doi.org/10.3390/md16060211 -
Abstract
The acid solubilised collagen (ASC) and pepsin solubilised collagen (PSC) were extracted from the by-products (skin) of a cartilaginous fish (Mustelus mustelus). The ASC and PSC yields were 23.07% and 35.27% dry weight, respectively and were identified as collagen Type I
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The acid solubilised collagen (ASC) and pepsin solubilised collagen (PSC) were extracted from the by-products (skin) of a cartilaginous fish (Mustelus mustelus). The ASC and PSC yields were 23.07% and 35.27% dry weight, respectively and were identified as collagen Type I with the presence of α, β and γ chains. As revealed by the Fourier Transform Infrared (FTIR) spectra analysis, pepsin did not alter the PSC triple helix structure. Based on the various type of collagen yield, only PSC was used in combination with chitosan to produce a composite film. Such film had lower tensile strength but higher elongation at break when compared to chitosan film; and lower water solubility and lightness when compared to collagen film. Equally, FTIR spectra analysis of film composite showed the occurrence of collagen-chitosan interaction resulting in a modification of the secondary structure of collagen. Collagen-chitosan-based biofilm showed a potential UV barrier properties and antioxidant activity, which might be used as green bioactive films to preserve nutraceutical products. Full article
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Open AccessArticle
Isolation and Structure Elucidation of Cembranoids from a Dongsha Atoll Soft Coral Sarcophyton stellatum
Mar. Drugs 2018, 16(6), 210; https://doi.org/10.3390/md16060210 -
Abstract
Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (13), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (716) from the ethyl acetate
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Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (13), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (716) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells. Full article
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Open AccessReview
Marine Myxobacteria: A Few Good Halophiles
Mar. Drugs 2018, 16(6), 209; https://doi.org/10.3390/md16060209 -
Abstract
Currently considered an excellent candidate source of novel chemical diversity, the existence of marine myxobacteria was in question less than 20 years ago. This review aims to serve as a roll call for marine myxobacteria and to summarize their unique features when compared
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Currently considered an excellent candidate source of novel chemical diversity, the existence of marine myxobacteria was in question less than 20 years ago. This review aims to serve as a roll call for marine myxobacteria and to summarize their unique features when compared to better-known terrestrial myxobacteria. Characteristics for discrimination between obligate halophilic, marine myxobacteria and halotolerant, terrestrial myxobacteria are discussed. The review concludes by highlighting the need for continued discovery and exploration of marine myxobacteria as producers of novel natural products. Full article
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Open AccessFeature PaperReview
Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails
Mar. Drugs 2018, 16(6), 208; https://doi.org/10.3390/md16060208 -
Abstract
Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have
[...] Read more.
Marine cone snails are a large family of gastropods that have evolved highly potent venoms for predation and defense. The cone snail venom has exceptional molecular diversity in neuropharmacologically active compounds, targeting a range of receptors, ion channels, and transporters. These conotoxins have helped to dissect the structure and function of many of these therapeutically significant targets in the central and peripheral nervous systems, as well as unravelling the complex cellular mechanisms modulated by these receptors and ion channels. This review provides an overview of α-conotoxins targeting neuronal nicotinic acetylcholine receptors. The structure and activity of both classical and non-classical α-conotoxins are discussed, along with their contributions towards understanding nicotinic acetylcholine receptor (nAChR) structure and function. Full article
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Open AccessArticle
The Holo-Transcriptome of the Zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa): A Plentiful Source of Enzymes for Potential Application in Green Chemistry, Industrial and Pharmaceutical Biotechnology
Mar. Drugs 2018, 16(6), 207; https://doi.org/10.3390/md16060207 -
Abstract
Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes.
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Marine invertebrates, such as sponges, tunicates and cnidarians (zoantharians and scleractinian corals), form functional assemblages, known as holobionts, with numerous microbes. This type of species-specific symbiotic association can be a repository of myriad valuable low molecular weight organic compounds, bioactive peptides and enzymes. The zoantharian Protopalythoa variabilis (Cnidaria: Anthozoa) is one such example of a marine holobiont that inhabits the coastal reefs of the tropical Atlantic coast and is an interesting source of secondary metabolites and biologically active polypeptides. In the present study, we analyzed the entire holo-transcriptome of P. variabilis, looking for enzyme precursors expressed in the zoantharian-microbiota assemblage that are potentially useful as industrial biocatalysts and biopharmaceuticals. In addition to hundreds of predicted enzymes that fit into the classes of hydrolases, oxidoreductases and transferases that were found, novel enzyme precursors with multiple activities in single structures and enzymes with incomplete Enzyme Commission numbers were revealed. Our results indicated the predictive expression of thirteen multifunctional enzymes and 694 enzyme sequences with partially characterized activities, distributed in 23 sub-subclasses. These predicted enzyme structures and activities can prospectively be harnessed for applications in diverse areas of industrial and pharmaceutical biotechnology. Full article
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Open AccessArticle
Smenamide A Analogues. Synthesis and Biological Activity on Multiple Myeloma Cells
Mar. Drugs 2018, 16(6), 206; https://doi.org/10.3390/md16060206 -
Abstract
Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A
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Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds. Full article
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Open AccessArticle
Absolute Configuration Determination of Retroflexanone Using the Advanced Mosher Method and Application of HPLC-NMR
Mar. Drugs 2018, 16(6), 205; https://doi.org/10.3390/md16060205 -
Abstract
The absolute configuration of retroflexanone (1) and a closely related phlorogluinol (2) was established using the advanced Mosher method and by application of HPLC-NMR. HPLC-NMR permitted a small scale Mosher method analysis to be carried out on these unstable phloroglucinols. Full article
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Open AccessArticle
Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90
Mar. Drugs 2018, 16(6), 204; https://doi.org/10.3390/md16060204 -
Abstract
Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in
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Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC50 1.4 and 2.7 μM after 24 h, respectively. In the xenograft animal model, the tumor size was significantly suppressed to about 51.9% in the heteronemin-treated group in comparison with the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay indicated that heteronemin could act as topoisomerase II (topo II) catalytic inhibitor through the elimination of essential enzymatic activity of topoisomerase IIα expression. We found that the use of heteronemin-triggered apoptosis by 20.1–68.3%, caused disruption of mitochondrial membrane potential (MMP) by 66.9–99.1% and promoted calcium release by 1.8-, 2.0-, and 2.1-fold compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, rhodamine 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished growth inhibition, oxidative and Endoplasmic Reticulum (ER) stress, as well as activation of Chop/Hsp70 induced by heteronemin, suggesting PTP activation plays a crucial rule in the cytotoxic activity of heteronemin. Using molecular docking analysis, heteronemin exhibited more binding affinity to the N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. Finally, heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells. Taken together, these multiple targets present heteronemin as an interesting candidate for its future development as an antiprostatic agent. Full article
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Open AccessReview
Exploring the Valuable Carotenoids for the Large-Scale Production by Marine Microorganisms
Mar. Drugs 2018, 16(6), 203; https://doi.org/10.3390/md16060203 -
Abstract
Carotenoids are among the most abundant natural pigments available in nature. These pigments have received considerable attention because of their biotechnological applications and, more importantly, due to their potential beneficial uses in human healthcare, food processing, pharmaceuticals and cosmetics. These bioactive compounds are
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Carotenoids are among the most abundant natural pigments available in nature. These pigments have received considerable attention because of their biotechnological applications and, more importantly, due to their potential beneficial uses in human healthcare, food processing, pharmaceuticals and cosmetics. These bioactive compounds are in high demand throughout the world; Europe and the USA are the markets where the demand for carotenoids is the highest. The in vitro synthesis of carotenoids has sustained their large-scale production so far. However, the emerging modern standards for a healthy lifestyle and environment-friendly practices have given rise to a search for natural biocompounds as alternatives to synthetic ones. Therefore, nowadays, biomass (vegetables, fruits, yeast and microorganisms) is being used to obtain naturally-available carotenoids with high antioxidant capacity and strong color, on a large scale. This is an alternative to the in vitro synthesis of carotenoids, which is expensive and generates a large number of residues, and the compounds synthesized are sometimes not active biologically. In this context, marine biomass has recently emerged as a natural source for both common and uncommon valuable carotenoids. Besides, the cultivation of marine microorganisms, as well as the downstream processes, which are used to isolate the carotenoids from these microorganisms, offer several advantages over the other approaches that have been explored previously. This review summarizes the general properties of the most-abundant carotenoids produced by marine microorganisms, focusing on the genuine/rare carotenoids that exhibit interesting features useful for potential applications in biotechnology, pharmaceuticals, cosmetics and medicine. Full article
Open AccessArticle
Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells
Mar. Drugs 2018, 16(6), 202; https://doi.org/10.3390/md16060202 -
Abstract
Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production
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Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1β), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells. Full article
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Open AccessArticle
Structural Characterisation of Predicted Helical Regions in the Chironex fleckeri CfTX-1 Toxin
Mar. Drugs 2018, 16(6), 201; https://doi.org/10.3390/md16060201 -
Abstract
The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins
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The Australian jellyfish Chironex fleckeri, belongs to a family of cubozoan jellyfish known for their potent venoms. CfTX-1 and -2 are two highly abundant toxins in the venom, but there is no structural data available for these proteins. Structural information on toxins is integral to the understanding of the mechanism of these toxins and the development of an effective treatment. Two regions of CfTX-1 have been predicted to have helical structures that are involved with the mechanism of action. Here we have synthesized peptides corresponding to these regions and analyzed their structures using NMR spectroscopy. The peptide corresponding to the predicted N-terminal amphiphilic helix appears unstructured in aqueous solution. This lack of structure concurs with structural disorder predicted for this region of the protein using the Protein DisOrder prediction System PrDOS. Conversely, a peptide corresponding to a predicted transmembrane region is very hydrophobic, insoluble in aqueous solution and predicted to be structured by PrDOS. In the presence of SDS-micelles both peptides have well-defined helical structures showing that a membrane mimicking environment stabilizes the structures of both peptides and supports the prediction of the transmembrane region in CfTX-1. This is the first study to experimentally analyze the structure of regions of a C. fleckeri protein. Full article
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Open AccessArticle
Tachypleus tridentatus Lectin Enhances Oncolytic Vaccinia Virus Replication to Suppress In Vivo Hepatocellular Carcinoma Growth
Mar. Drugs 2018, 16(6), 200; https://doi.org/10.3390/md16060200 -
Abstract
Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse
[...] Read more.
Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Further investigations revealed that oncoVV-TTL replication was highly dependent on ERK activity. This study might provide insights into a novel way of the utilization of TTL in oncolytic viral therapies. Full article
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Open AccessArticle
Albisporachelin, a New Hydroxamate Type Siderophore from the Deep Ocean Sediment-Derived Actinomycete Amycolatopsisalbispora WP1T
Mar. Drugs 2018, 16(6), 199; https://doi.org/10.3390/md16060199 -
Abstract
Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1T was isolated
[...] Read more.
Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1T was isolated from sediments collected at −2945 m in the Indian Ocean. The new siderophore, designated albisporachelin, was isolated from iron depleted culture broths and the structure was established by 1D and 2D NMR and MS/MS experiments, and application of a modified Marfey’s method. Albisporachelin is composed of one N-methylated-formylated/hydroxylated l-ornithine (N-Me-fh-l-Orn), one l-serine (l-Ser), one formylated/hydroxylated l-ornithine (fh-l-Orn) and a cyclo-N-methylated-hydroxylated l-ornithine (cyclo-N-Me-h-l-Orn). Full article
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Open AccessFeature PaperArticle
Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis
Mar. Drugs 2018, 16(6), 198; https://doi.org/10.3390/md16060198 -
Abstract
Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a
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Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment. Full article
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