Open AccessArticle
Brown Algae Padina sanctae-crucis Børgesen: A Potential Nutraceutical
Mar. Drugs 2017, 15(10), 251; doi:10.3390/md15100251 (registering DOI) -
Abstract
Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina;
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Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of P.sanctae-crucis presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since Padina sanctae-crucis is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical. Full article
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Open AccessArticle
Effect of Protonation State and N-Acetylation of Chitosan on Its Interaction with Xanthan Gum: A Molecular Dynamics Simulation Study
Mar. Drugs 2017, 15(10), 298; doi:10.3390/md15100298 (registering DOI) -
Abstract
Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information
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Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect. Full article
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Open AccessReview
Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms
Mar. Drugs 2017, 15(10), 297; doi:10.3390/md15100297 (registering DOI) -
Abstract
There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to
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There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceutical applications. Many types of bioactive secondary metabolites from marine algae, including phlorotannins, sulfated polysaccharides, carotenoids, and meroterpenoids, have already been documented for their potential applications in the pharmaceutical industry. Among these metabolites, phlorotannins from brown algae have been widely screened for their pharmaceutical and hypopigmenting effects. Unfortunately, the majority of these articles did not have detailed investigations on molecular targets, which is critical to fulfilling the criteria for their cosmeceutical and pharmaceutical use. Very recently, a few meroterpenoids have been discovered from Sargassum sp., with the examination of their anti-melanogenic properties and mechanisms. Despite the scarcity of in vivo and clinical investigations of molecular mechanistic events of marine algae-derived hypopigmenting agents, identifying the therapeutic targets and their validation in humans has been a major challenge for future studies. In this review, we focused on available data representing molecular mechanisms underlying hypopigmenting properties of potential marine brown alga-derived compounds. Full article
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Open AccessReview
µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic Potential
Mar. Drugs 2017, 15(10), 295; doi:10.3390/md15100295 -
Abstract
The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of
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The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). Each species is able to produce up to 200 different biological active peptides. Common structure of CTX is the low number of amino acids stabilized by disulfide bridges and post-translational modifications that give rise to different isoforms. µ and µO-CTX are two isoforms that specifically target voltage-gated sodium channels. These, by inducing the entrance of sodium ions in the cell, modulate the neuronal excitability by depolarizing plasma membrane and propagating the action potential. Hyperexcitability and mutations of sodium channels are responsible for perception and transmission of inflammatory and neuropathic pain states. In this review, we describe the current knowledge of µ-CTX interacting with the different sodium channels subtypes, the mechanism of action and their potential therapeutic use as analgesic compounds in the clinical management of pain conditions. Full article
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Open AccessArticle
Metabolic Engineering of Escherichia coli for Producing Astaxanthin as the Predominant Carotenoid
Mar. Drugs 2017, 15(10), 296; doi:10.3390/md15100296 -
Abstract
Astaxanthin is a carotenoid of significant commercial value due to its superior antioxidant potential and wide applications in the aquaculture, food, cosmetic and pharmaceutical industries. A higher ratio of astaxanthin to the total carotenoids is required for efficient astaxanthin production. β-Carotene ketolase and
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Astaxanthin is a carotenoid of significant commercial value due to its superior antioxidant potential and wide applications in the aquaculture, food, cosmetic and pharmaceutical industries. A higher ratio of astaxanthin to the total carotenoids is required for efficient astaxanthin production. β-Carotene ketolase and hydroxylase play important roles in astaxanthin production. We first compared the conversion efficiency to astaxanthin in several β-carotene ketolases from Brevundimonas sp. SD212, Sphingomonas sp. DC18, Paracoccus sp. PC1, P. sp. N81106 and Chlamydomonas reinhardtii with the recombinant Escherichia coli cells that synthesize zeaxanthin due to the presence of the Pantoea ananatis crtEBIYZ. The B. sp. SD212 crtW and P. ananatis crtZ genes are the best combination for astaxanthin production. After balancing the activities of β-carotene ketolase and hydroxylase, an E. coli ASTA-1 that carries neither a plasmid nor an antibiotic marker was constructed to produce astaxanthin as the predominant carotenoid (96.6%) with a specific content of 7.4 ± 0.3 mg/g DCW without an addition of inducer. Full article
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Open AccessArticle
Anti-Inflammatory Effects of a Mytilus coruscus α-d-Glucan (MP-A) in Activated Macrophage Cells via TLR4/NF-κB/MAPK Pathway Inhibition
Mar. Drugs 2017, 15(9), 294; doi:10.3390/md15090294 -
Abstract
The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A,
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The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction. Full article
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Open AccessArticle
Proteomic Analysis of the Chlorophyta Dunaliella New Strain AL-1 Revealed Global Changes of Metabolism during High Carotenoid Production
Mar. Drugs 2017, 15(9), 293; doi:10.3390/md15090293 -
Abstract
The green microalgae Dunaliella genus is known for the production of high added value molecules. In this study, strain AL-1 was isolated from the Sebkha of Sidi El Hani (Sousse, Tunisia). This isolate was identified both morphologically and genetically via 18S rRNA gene
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The green microalgae Dunaliella genus is known for the production of high added value molecules. In this study, strain AL-1 was isolated from the Sebkha of Sidi El Hani (Sousse, Tunisia). This isolate was identified both morphologically and genetically via 18S rRNA gene sequence as a member of the genus Dunaliella. Strain AL-1 was found to be closely related to Dunaliella salina, Dunaliella quartolecta and Dunaliella polymorpha with more than 97% similarity. Response surface methodology was used to maximize carotenoid production by strain AL-1 by optimizing its growth conditions. The highest carotenoid content was obtained at salinity: 51, light intensity: 189.89 μmol photons·m−2·s−1, and nitrogen: 60 mg·L−1. Proteomic profiling, using two-dimensional gel electrophoresis, was performed from standard and optimized cultures. We detected 127 protein spots which were significantly differentially expressed between standard and optimized cultures. Among them 16 protein spots were identified with mass spectrometry and grouped into different functional categories using KEGG (Kyoto Encyclopedia of Genes and Genomes) such as photosynthetic Calvin cycle, regulation/defense, energy metabolism, glycolysis, and cellular processes. The current study could be of great interest in providing information on the effect of stressful conditions in microalgae carotenoid production. Full article
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Open AccessCorrection
Correction: Zhang, G.; Cheng, G.; Jia, P.; Jiao, S.; Feng, C.; Hu, T.; Liu, H.; Du, Y. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree. Marine Drugs 2017, 15, 236
Mar. Drugs 2017, 15(9), 292; doi:10.3390/md15090292 -
Abstract
The authors wish to correct Figure 1 in this paper [1] to be as follows:[...] Full article
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Open AccessArticle
Chemical Synthesis of Marine-Derived Sulfoglycolipids, a New Class of Molecular Adjuvants
Mar. Drugs 2017, 15(9), 288; doi:10.3390/md15090288 -
Abstract
Vaccines play a primary role in the protection of human health by preventing infectious and chronic diseases. Recently we have reported 1,2-O-distearoyl-3-O-β-d-sulfoquinovosylglycerol (β-SQDG18), here named Sulfavant A (1), which shows promising properties as a new
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Vaccines play a primary role in the protection of human health by preventing infectious and chronic diseases. Recently we have reported 1,2-O-distearoyl-3-O-β-d-sulfoquinovosylglycerol (β-SQDG18), here named Sulfavant A (1), which shows promising properties as a new molecular adjuvant in in vitro and in vivo tests. In the present manuscript, we provide full details about a synthetic strategy for the preparation of 1, including a discussion of chemical determinants of the activity and the major technical hurdles we faced during the study. Synthesis of Sulfavant A (1) is achieved by a versatile procedure based on a trichloroacetimidate methodology and peracetate sugar precursors. The final design opens possibilities for the preparation of a series of interesting analogs for further pharmacological optimization and development, including derivatives containing different saturated and polyunsaturated fatty acids (e.g., 17 and 22). Full article
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Open AccessArticle
3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes
Mar. Drugs 2017, 15(9), 291; doi:10.3390/md15090291 -
Abstract
A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of
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A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal–regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway. Full article
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Open AccessArticle
Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer
Mar. Drugs 2017, 15(9), 290; doi:10.3390/md15090290 -
Abstract
Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N
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Kempopeptin C, a novel chlorinated analogue of kempopeptin B, was discovered from a marine cyanobacterium collected from Kemp Channel in Florida. The structure was elucidated using NMR spectroscopy and mass spectrometry (MS). The presence of the basic Lys residue adjacent to the N-terminus of the 3-amino-6-hydroxy-2-piperidone (Ahp) moiety contributed to its selectivity towards trypsin and related proteases. The antiproteolytic activity of kempopeptin C was evaluated against trypsin, plasmin and matriptase and found to inhibit these enzymes with IC50 values of 0.19, 0.36 and 0.28 μM, respectively. Due to the significance of these proteases in cancer progression and metastasis, as well as their functional redundancy with respect to targeting overlapping substrates, we examined the effect of kempopeptin C on the downstream cellular substrates of matriptase: CDCP1 and desmoglein-2 (Dsg-2). Kempopeptin C was shown to inhibit the cleavage of both substrates in vitro. Additionally, kempopeptin C reduced the cleavage of CDCP1 in MDA-MB-231 cells up to 10 µM. The functional relevance of targeting matriptase and related proteases was investigated by assessing the effect of kempopeptin C on the migration of breast cancer cells. Kempopeptin C inhibited the migration of the invasive MDA-MB-231 cells by 37 and 60% at 10 and 20 µM, respectively. Full article
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Open AccessArticle
Leptolide Improves Insulin Resistance in Diet-Induced Obese Mice
Mar. Drugs 2017, 15(9), 289; doi:10.3390/md15090289 -
Abstract
Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell
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Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity. To this end, we tested the hypothesis that leptolide should protect against fatty acid-induced insulin resistance in hepatocytes. In a time-dependent manner, leptolide (0.1 µM) augmented insulin-stimulated phosphorylation of protein kinase B (PKB) by two-fold above vehicle-treated HepG2 cells. In addition, leptolide (0.1 µM) counteracted palmitate-induced insulin resistance by augmenting by four-fold insulin-stimulated phosphorylation of PKB in HepG2 cells. In vivo, acute intraperitoneal administration of leptolide (0.1 mg/kg and 1 mg/kg) improved glucose tolerance and insulin sensitivity in lean mice. Likewise, prolonged leptolide treatment (0.1 mg/kg) in diet-induced obese mice improved insulin sensitivity. These effects were paralleled with an ~50% increased of insulin-stimulated phosphorylation of PKB in liver and skeletal muscle and reduced circulating pro-inflammatory cytokines in obese mice. We concluded that leptolide significantly improves insulin sensitivity in vitro and in obese mice, suggesting that leptolide may be another potential treatment for T2DM. Full article
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Open AccessArticle
APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel KV10.1
Mar. Drugs 2017, 15(9), 287; doi:10.3390/md15090287 -
Abstract
The human ether-à-go-go channel (hEag1 or KV10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer
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The human ether-à-go-go channel (hEag1 or KV10.1) is a cancer-relevant voltage-gated potassium channel that is overexpressed in a majority of human tumors. Peptides that are able to selectively inhibit this channel can be lead compounds in the search for new anticancer drugs. Here, we report the activity-guided purification and electrophysiological characterization of a novel KV10.1 inhibitor from the sea anemone Anthopleura elegantissima. Purified sea anemone fractions were screened for inhibitory activity on KV10.1 by measuring whole-cell currents as expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp technique. Fractions that showed activity on Kv10.1 were further purified by RP-HPLC. The amino acid sequence of the peptide was determined by a combination of MALDI- LIFT-TOF/TOF MS/MS and CID-ESI-FT-ICR MS/MS and showed a high similarity with APETx1 and APETx3 and was therefore named APETx4. Subsequently, the peptide was electrophysiologically characterized on KV10.1. The selectivity of the toxin was investigated on an array of voltage-gated ion channels, including the cardiac human ether-à-go-go-related gene potassium channel (hERG or Kv11.1). The toxin inhibits KV10.1 with an IC50 value of 1.1 μM. In the presence of a similar toxin concentration, a shift of the activation curve towards more positive potentials was observed. Similar to the effect of the gating modifier toxin APETx1 on hERG, the inhibition of Kv10.1 by the isolated toxin is reduced at more positive voltages and the peptide seems to keep the channel in a closed state. Although the peptide also induces inhibitory effects on other KV and NaV channels, it exhibits no significant effect on hERG. Moreover, APETx4 induces a concentration-dependent cytotoxic and proapoptotic effect in various cancerous and noncancerous cell lines. This newly identified KV10.1 inhibitor can be used as a tool to further characterize the oncogenic channel KV10.1 or as a scaffold for the design and synthesis of more potent and safer anticancer drugs. Full article
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Open AccessArticle
Biodiversity of Actinobacteria from the South Pacific and the Assessment of Streptomyces Chemical Diversity with Metabolic Profiling
Mar. Drugs 2017, 15(9), 286; doi:10.3390/md15090286 -
Abstract
Recently, bioprospecting in underexplored habitats has gained enhanced focus, since new taxa of marine actinobacteria can be found, and thus possible new metabolites. Actinobacteria are in the foreground due to their versatile production of secondary metabolites that present various biological activities, such as
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Recently, bioprospecting in underexplored habitats has gained enhanced focus, since new taxa of marine actinobacteria can be found, and thus possible new metabolites. Actinobacteria are in the foreground due to their versatile production of secondary metabolites that present various biological activities, such as antibacterials, antitumorals and antifungals. Chilean marine ecosystems remain largely unexplored and may represent an important source for the discovery of bioactive compounds. Various culture conditions to enrich the growth of this phylum were used and 232 bacterial strains were isolated. Comparative analysis of the 16S rRNA gene sequences led to identifying genetic affiliations of 32 genera, belonging to 20 families. This study shows a remarkable culturable diversity of actinobacteria, associated to marine environments along Chile. Furthermore, 30 streptomycete strains were studied to establish their antibacterial activities against five model strains, Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa, demonstrating abilities to inhibit bacterial growth of Gram-positive bacteria. To gain insight into their metabolic profiles, crude extracts were submitted to liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis to assess the selection of streptomycete strains with potentials of producing novel bioactive metabolites. The combined approach allowed for the identification of three streptomycete strains to pursue further investigations. Our Chilean marine actinobacterial culture collection represents an important resource for the bioprospection of novel marine actinomycetes and its metabolites, evidencing their potential as producers of natural bioproducts. Full article
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Open AccessReview
Biogenetic Relationships of Bioactive Sponge Merotriterpenoids
Mar. Drugs 2017, 15(9), 285; doi:10.3390/md15090285 -
Abstract
Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied.
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Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied. In this review, an in depth structural analysis of sponge merotriterpenoids, including the adociasulfate family of kinesin motor protein inhibitors, provides insight into their biosynthesis. Several key structural features provide clues to the relationships between compounds. All adociasulfates appear to be derived from only four different hydroquinone hexaprenyl diphosphate precursors, each varying in the number and position of epoxidations. Proton-initiated cyclization of these precursors can lead to all carbon skeletons observed amongst sponge merotriterpenoids. Consideration of the enzymes involved in the proposed biosynthetic route suggests a bacterial source, and a hypothetical gene cluster was constructed that may facilitate discovery of the authentic pathway from the sponge metagenome. A similar rationale can be extended to other sponge meroterpenoids, for which no biosynthetic pathways have yet been identified. Full article
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Open AccessArticle
Potential Application of Eicosapentaenoic Acid Monoacylglyceride in the Management of Colorectal Cancer
Mar. Drugs 2017, 15(9), 283; doi:10.3390/md15090283 -
Abstract
Background: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the
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Background: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. Methods: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft. Results: Our data reveal that MAG-EPA decreased cell proliferation and induced apoptosis in HCT116 cells. In a xenograft mouse model, daily per os administration of MAG-EPA reduced tumor growth. Furthermore, MAG-EPA treatments decreased EGFR, VEGFR, and AKT activation pathways and reduced VEGF and HIF1α expression levels in tumors. Conclusion: MAG-EPA may promote apoptosis and inhibit growth of tumors by suppressing EGFR and VEGFR activation pathways. Altogether, these data provide new evidence regarding the mode of action of MAG-EPA in colorectal cancer cells. Full article
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Open AccessArticle
Construction of a Fluorescent H2O2 Biosensor with Chitosan 6-OH Immobilized β-Cyclodextrin Derivatives
Mar. Drugs 2017, 15(9), 284; doi:10.3390/md15090284 -
Abstract
In the present work, a fluorescent H2O2 biosensor was constructed by encapsulating fluorescent probe Rhodamine B (RhmB) in the hydrophobic cavity of the cyclodextrin (β-CD) and immobilizing catalase (CAT) on the 2-NH2 of chitosan (CTS) in a chitosan 6-OH
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In the present work, a fluorescent H2O2 biosensor was constructed by encapsulating fluorescent probe Rhodamine B (RhmB) in the hydrophobic cavity of the cyclodextrin (β-CD) and immobilizing catalase (CAT) on the 2-NH2 of chitosan (CTS) in a chitosan 6-OH immobilized β-cyclodextrin derivative (CTS-6-CD). The inclusion complex of CTS-6-CD to RhmB (CTS-6-CD-RhmB) was prepared by a solution method. Its structure and inclusion efficiency were determined by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and fluorescence spectroscopy (FL). CAT was immobilized on CTS-6-CD-RhmB to eventually form the functional membrane, CTS-6-CD-RhmB-CAT, via glutaraldehyde crosslinking, which was further characterized by FTIR and FL, and used as a H2O2 biosensor. The functional membrane was used to simultaneously oxidize and detect H2O2. The detection condition was optimized as pH 8, a reaction temperature of 25 °C, and an immobilized enzyme concentration of 2 × 10−4 mol/L. The fluorescence response of the biosensor exhibited a good linear relationship with the concentration of H2O2 in the range of 20 mΜ–300 μM and the detection limit of 10−8 mol/L. Full article
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Open AccessArticle
Anti-Inflammatory Effects of Curvularin-Type Metabolites from a Marine-Derived Fungal Strain Penicillium sp. SF-5859 in Lipopolysaccharide-Induced RAW264.7 Macrophages
Mar. Drugs 2017, 15(9), 282; doi:10.3390/md15090282 -
Abstract
Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (29). The structures of these metabolites (19) were
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Chemical study on the extract of a marine-derived fungal strain Penicillium sp. SF-5859 yielded a new curvularin derivative (1), along with eight known curvularin-type polyketides (29). The structures of these metabolites (19) were established by comprehensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). In vitro anti-inflammatory effects of these metabolites were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Among these metabolites, 39 were shown to strongly inhibit LPS-induced overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) with IC50 values ranging from 1.9 μM to 18.1 μM, and from 2.8 μM to 18.7 μM, respectively. In the further evaluation of signal pathways involved in these effects, the most active compound, (10E,15S)-10,11-dehydrocurvularin (8) attenuated the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 macrophages. Furthermore, compound 8 was shown to suppress the upregulation of pro-inflammatory mediators and cytokines via the inhibition of the nuclear factor-κB (NF-κB) signaling pathway, but not through the mitogen-activated protein kinase (MAPK) pathway. Based on the comparisons of the different magnitude of the anti-inflammatory effects of these structurally-related metabolites, it was suggested that the opening of the 12-membered lactone ring in curvularin-type metabolites and blocking the phenol functionality led to the significant decrease in their anti-inflammatory activity. Full article
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Open AccessArticle
Bioactive Steroids with Methyl Ester Group in the Side Chain from a Reef Soft Coral Sinularia brassica Cultured in a Tank
Mar. Drugs 2017, 15(9), 280; doi:10.3390/md15090280 -
Abstract
A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica,which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1
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A continuing chemical investigation of the ethyl acetate (EtOAc) extract of a reef soft coral Sinularia brassica,which was cultured in a tank, afforded four new steroids with methyl ester groups, sinubrasones A–D (1–4) for the first time. In particular, 1 possesses a β-D-xylopyranose. The structures of the new compounds were elucidated on the basis of spectroscopic analyses. The cytotoxicities of compounds 1–4 against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of these new compounds 1–4 were also evaluated by measuring their ability to suppress superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. Compounds 2 and 3 were shown to exhibit significant cytotoxicity, and compounds 3 and 4 were also found to display attracting anti-inflammatory activities. Full article
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Open AccessArticle
Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats
Mar. Drugs 2017, 15(9), 279; doi:10.3390/md15090279 -
Abstract
We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2%
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We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23.5% (bile-depleted) with taurocholate supplementation (60 mg/kg). Consistent with the increased absorption in the presence of bile salts, rat intestinal permeability of Jaspine B also increased in the presence of 10 mM taurocholate or 20% bile. Further studies demonstrated that the enhanced intestinal permeability with bile salts was due to increased lipophilicity and decreased membrane integrity. Jaspine B was designated as a highly tissue-distributed compound, because it showed large tissue to plasma ratios in the brain, kidney, heart, and spleen. Moreover, the recovery of Jaspine B from the feces and urine after an intravenous administration was about 6.3%, suggesting a substantial metabolism of Jaspine B. Consistent with this observation, 80% of the administered Jaspine B was degraded after 1 h incubation with rat liver microsomes. In conclusion, the facilitated intestinal permeability in the presence of bile salts could significantly increase the bioavailability of Jaspine B and could lead to the development of oral formulations of Jaspine B with bile salts. Moreover, the highly distributed features of Jaspine B in the brain, kidney, heart, and spleen should be carefully considered in the therapeutic effect and toxicity of this compound. Full article
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