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Mar. Drugs, Volume 13, Issue 11 (November 2015), Pages 6550-7054

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Open AccessArticle Purification and Characterization of Cathepsin B from the Muscle of Horse Mackerel Trachurus japonicus
Mar. Drugs 2015, 13(11), 6550-6565; doi:10.3390/md13116550
Received: 31 August 2015 / Revised: 11 October 2015 / Accepted: 14 October 2015 / Published: 28 October 2015
Cited by 3 | PDF Full-text (2843 KB) | HTML Full-text | XML Full-text
Abstract
An endogenous protease in fish muscle, cathepsin B, was partially purified and characterized from horse mackerel meat. On SDS-PAGE of the purified enzyme under reducing conditions, main protein bands were detected at 28 and 6 kDa and their respective N-terminal sequences showed high
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An endogenous protease in fish muscle, cathepsin B, was partially purified and characterized from horse mackerel meat. On SDS-PAGE of the purified enzyme under reducing conditions, main protein bands were detected at 28 and 6 kDa and their respective N-terminal sequences showed high homology to heavy and light chains of cathepsin B from other species. This suggested that horse mackerel cathepsin B formed two-chain forms, similar to mammalian cathepsin Bs. Optimum pH and temperature of the enzyme were 5.0 and 50 °C, respectively. A partial cDNA encoding the amino acid sequence of 215 residues for horse mackerel cathepsin B was obtained by RT-PCR and cloned. The deduced amino acid sequence contains a part of light and heavy chains of cathepsin B. The active sites and an N-glycosylation site were conserved across species. We also confirmed that the modori phenomenon was avoided by CA-074, a specific inhibitor for cathepsin B. Therefore, our results suggest that natural cysteine protease inhibitor(s), such as oryzacystatin derived from rice, can apply to thermal-gel processing of horse mackerel to avoid the modori phenomenon. Meanwhile, this endogenous protease may be used for food processing, such as weaning meal and food for the elderly. Full article
(This article belongs to the Special Issue Green Chemistry Approach to Marine Products)
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Open AccessArticle Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
Mar. Drugs 2015, 13(11), 6588-6608; doi:10.3390/md13116588
Received: 29 July 2015 / Revised: 18 September 2015 / Accepted: 19 October 2015 / Published: 28 October 2015
Cited by 3 | PDF Full-text (1701 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of
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Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases. Full article
(This article belongs to the collection Marine Polysaccharides)
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Open AccessArticle Bioactive Hydantoin Alkaloids from the Red Sea Marine Sponge Hemimycale arabica
Mar. Drugs 2015, 13(11), 6609-6619; doi:10.3390/md13116609
Received: 13 September 2015 / Revised: 16 October 2015 / Accepted: 26 October 2015 / Published: 28 October 2015
Cited by 10 | PDF Full-text (489 KB) | HTML Full-text | XML Full-text
Abstract
In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine invertebrates, we have investigated the sponge Hemimycale arabica. The antimicrobial fraction of an organic extract of the sponge afforded two new hydantoin alkaloids, hemimycalins A and
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In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine invertebrates, we have investigated the sponge Hemimycale arabica. The antimicrobial fraction of an organic extract of the sponge afforded two new hydantoin alkaloids, hemimycalins A and B (2 and 3), together with the previously reported compound (Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione (1). The structures of the compounds were determined by extensive 1D and 2D NMR (COSY, HSQC and HMBC) studies and high-resolution mass spectral determinations. Hemimycalins A (2) and B (3) represent the first examples of the natural N-alkylated hydantoins from the sponge Hemimycale arabica. Compounds 13 displayed variable antimicrobial activities against E. coli, S. aureus, and C. albicans. In addition, compound 1 displayed moderate antiproliferative activity against the human cervical carcinoma (HeLa) cell line. These findings provide further insight into the chemical diversity as well as the biological activity of this class of compounds. Full article
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Open AccessArticle Isolation and Analysis of the Cppsy Gene and Promoter from Chlorella protothecoides CS-41
Mar. Drugs 2015, 13(11), 6620-6635; doi:10.3390/md13116620
Received: 25 June 2015 / Revised: 9 September 2015 / Accepted: 9 September 2015 / Published: 28 October 2015
Cited by 1 | PDF Full-text (1117 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytoene synthase (PSY) catalyzes the condensation of two molecules of geranylgeranyl pyrophosphate to form phytoene, the first colorless carotene in the carotenoid biosynthesis pathway. So it is regarded as the crucial enzyme for carotenoid production, and has unsurprisingly been involved in genetic engineering
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Phytoene synthase (PSY) catalyzes the condensation of two molecules of geranylgeranyl pyrophosphate to form phytoene, the first colorless carotene in the carotenoid biosynthesis pathway. So it is regarded as the crucial enzyme for carotenoid production, and has unsurprisingly been involved in genetic engineering studies of carotenoid production. In this study, the psy gene from Chlorella protothecoides CS-41, designated Cppsy, was cloned using rapid amplification of cDNA ends. The full-length DNA was 2488 bp, and the corresponding cDNA was 1143 bp, which encoded 380 amino acids. Computational analysis suggested that this protein belongs to the Isoprenoid_Biosyn_C1 superfamily. It contained the consensus sequence, including three predicted substrate-Mg2+ binding sites. The Cppsy gene promoter was also cloned and characterized. Analysis revealed several candidate motifs for the promoter, which exhibited light- and methyl jasmonate (MeJA)-responsive characteristics, as well as some typical domains universally discovered in promoter sequences, such as the TATA-box and CAAT-box. Light- and MeJA treatment showed that the Cppsy expression level was significantly enhanced by light and MeJA. These results provide a basis for genetically modifying the carotenoid biosynthesis pathway in C. protothecoides. Full article
(This article belongs to the Special Issue Marine Carotenoids (Special Issue))
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Open AccessArticle Nitric Oxide Synthase in the Central Nervous System and Peripheral Organs of Stramonita haemastoma: Protein Distribution and Gene Expression in Response to Thermal Stress
Mar. Drugs 2015, 13(11), 6636-6664; doi:10.3390/md13116636
Received: 10 August 2015 / Revised: 15 October 2015 / Accepted: 19 October 2015 / Published: 30 October 2015
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Abstract
Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing
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Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing structural and functional characteristics with nNOS or iNOS depending on the species. The present paper is focused on the constitutive Ca2+/calmodulin-dependent nNOS recently sequenced by our group in the neogastropod Stramonita haemastoma (ShNOS). In this paper we provide new data on cellular distribution of ShNOS in the CNS (pedal ganglion) and peripheral organs (osphradium, tentacle, eye and foot) obtained by WB, IF, CM and NADPHd. Results demonstrated that NOS-like proteins are widely expressed in sensory receptor elements, neurons and epithelial cells. The detailed study of NOS distribution in peripheral and central neurons suggested that NOS is both intracellular and presynaptically located. Present findings confirm that NO may have a key role in the central neuronal circuits of gastropods and in sensory perception. The physiological relevance of NOS enzymes in the same organs was suggested by thermal stress experiments demonstrating that the constitutive expression of ShNOS is modulated in a time- and organ-dependent manner in response to environmental stressors. Full article
(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)
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Open AccessArticle Structure Elucidation and in Vitro Toxicity of New Azaspiracids Isolated from the Marine Dinoflagellate Azadinium poporum
Mar. Drugs 2015, 13(11), 6687-6702; doi:10.3390/md13116687
Received: 14 April 2015 / Revised: 14 June 2015 / Accepted: 14 October 2015 / Published: 30 October 2015
Cited by 9 | PDF Full-text (547 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two strains of Azadinium poporum, one from the Korean West coast and the other from the North Sea, were mass cultured for isolation of new azaspiracids. Approximately 0.9 mg of pure AZA-36 (1) and 1.3 mg of pure AZA-37 (
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Two strains of Azadinium poporum, one from the Korean West coast and the other from the North Sea, were mass cultured for isolation of new azaspiracids. Approximately 0.9 mg of pure AZA-36 (1) and 1.3 mg of pure AZA-37 (2) were isolated from the Korean (870 L) and North Sea (120 L) strains, respectively. The structures were determined to be 3-hydroxy-8-methyl-39-demethyl-azaspiracid-1 (1) and 3-hydroxy-7,8-dihydro-39-demethyl-azaspiracid-1 (2) by 1H- and 13C-NMR. Using the Jurkat T lymphocyte cell toxicity assay, (1) and (2) were found to be 6- and 3-fold less toxic than AZA-1, respectively. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
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Open AccessArticle Effects of Cylindrospermopsin Producing Cyanobacterium and Its Crude Extracts on a Benthic Green Alga—Competition or Allelopathy?
Mar. Drugs 2015, 13(11), 6703-6722; doi:10.3390/md13116703
Received: 30 August 2015 / Revised: 20 October 2015 / Accepted: 26 October 2015 / Published: 30 October 2015
Cited by 3 | PDF Full-text (1071 KB) | HTML Full-text | XML Full-text
Abstract
Cylindrospermopsin (CYN) is a toxic secondary metabolite produced by filamentous cyanobacteria which could work as an allelopathic substance, although its ecological role in cyanobacterial-algal assemblages is mostly unclear. The competition between the CYN-producing cyanobacterium Chrysosporum (Aphanizomenon) ovalisporum, and the benthic
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Cylindrospermopsin (CYN) is a toxic secondary metabolite produced by filamentous cyanobacteria which could work as an allelopathic substance, although its ecological role in cyanobacterial-algal assemblages is mostly unclear. The competition between the CYN-producing cyanobacterium Chrysosporum (Aphanizomenon) ovalisporum, and the benthic green alga Chlorococcum sp. was investigated in mixed cultures, and the effects of CYN-containing cyanobacterial crude extract on Chlorococcum sp. were tested by treatments with crude extracts containing total cell debris, and with cell debris free crude extracts, modelling the collapse of a cyanobacterial water bloom. The growth inhibition of Chlorococcum sp. increased with the increasing ratio of the cyanobacterium in mixed cultures (inhibition ranged from 26% to 87% compared to control). Interestingly, inhibition of the cyanobacterium growth also occurred in mixed cultures, and it was more pronounced than it was expected. The inhibitory effects of cyanobacterial crude extracts on Chlorococcum cultures were concentration-dependent. The presence of C. ovalisporum in mixed cultures did not cause significant differences in nutrient content compared to Chlorococcum control culture, so the growth inhibition of the green alga could be linked to the presence of CYN and/or other bioactive compounds. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Open AccessArticle Structure of an Amino Acid-Decorated Exopolysaccharide Secreted by a Vibrio alginolyticus Strain
Mar. Drugs 2015, 13(11), 6723-6739; doi:10.3390/md13116723
Received: 17 August 2015 / Revised: 16 October 2015 / Accepted: 22 October 2015 / Published: 30 October 2015
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Abstract
Vibrio alginolyticus (CNCM I-4994) secretes an exopolysaccharide that can be used as an ingredient in cosmetic applications. The structure was resolved using chromatography and one- and two-dimensional NMR spectroscopy experiments. The results show that the carbohydrate backbone is made of two residues: d-galacturonic
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Vibrio alginolyticus (CNCM I-4994) secretes an exopolysaccharide that can be used as an ingredient in cosmetic applications. The structure was resolved using chromatography and one- and two-dimensional NMR spectroscopy experiments. The results show that the carbohydrate backbone is made of two residues: d-galacturonic acid and N-acetyl-d-glucosamine (GlcNac), which together constitute a tetrasaccharide repetition unit: [→3)-α-d-GalA-(1→4)-α-d-GalA-(1→3)-α-d-GalA-(1→3)-β-GlcNAc(1→]. Two amino acids, alanine and serine, are linked to GalA residues via amido linkages. The position and the distribution of the amino acids were characterized by two-dimensional NMR spectroscopy. To our knowledge, this is the first description of a structure for a marine exopolysaccharide decorated with an amino acid. Full article
(This article belongs to the Special Issue Marine Glycoconjugates)
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Open AccessArticle Seasonal Changes in Mycosporine-Like Amino Acid Production Rate with Respect to Natural Phytoplankton Species Composition
Mar. Drugs 2015, 13(11), 6740-6758; doi:10.3390/md13116740
Received: 2 September 2015 / Revised: 1 October 2015 / Accepted: 7 October 2015 / Published: 6 November 2015
Cited by 1 | PDF Full-text (417 KB) | HTML Full-text | XML Full-text
Abstract
After in situ incubation at the site for a year, phytoplanktons in surface water were exposed to natural light in temperate lakes (every month); thereafter, the net production rate of photoprotective compounds (mycosporine-like amino acids, MAAs) was calculated using 13C labeled tracer.
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After in situ incubation at the site for a year, phytoplanktons in surface water were exposed to natural light in temperate lakes (every month); thereafter, the net production rate of photoprotective compounds (mycosporine-like amino acids, MAAs) was calculated using 13C labeled tracer. This is the first report describing seasonal variation in the net production rate of individual MAAs in temperate lakes using a compound-specific stable isotope method. In the mid-latitude region of the Korean Peninsula, UV radiation (UVR) usually peaks from July to August. In Lake Paldang and Lake Cheongpyeong, diatoms dominated among the phytoplankton throughout the year. The relative abundance of Cyanophyceae (Anabaena spiroides) reached over 80% during July in Lake Cheongpyeong. Changes in phytoplankton abundance indicate that the phytoplankton community structure is influenced by seasonal changes in the net production rate and concentration of MAAs. Notably, particulate organic matter (POM) showed a remarkable change based on the UV intensity occurring during that period; this was because of the fact that cyanobacteria that are highly sensitive to UV irradiance dominated the community. POM cultured in Lake Paldang had the greatest shinorine (SH) production rate during October, i.e., 83.83 ± 10.47 fgC·L−1·h−1. The dominance of diatoms indicated that they had a long-term response to UVR. Evaluation of POM cultured in Lake Cheongpyeong revealed that there was an increase in the net MAA production in July (when UVR reached the maximum); a substantial amount of SH, i.e., 17.62 ± 18.34 fgC·L−1·h−1, was recorded during this period. Our results demonstrate that both the net production rate as well as the concentration of MAAs related to photoinduction depended on the phytoplankton community structure. In addition, seasonal changes in UVR also influenced the quantity and production of MAAs in phytoplanktons (especially Cyanophyceae). Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Open AccessArticle Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay
Mar. Drugs 2015, 13(11), 6759-6773; doi:10.3390/md13116759
Received: 19 September 2015 / Revised: 23 October 2015 / Accepted: 23 October 2015 / Published: 6 November 2015
Cited by 7 | PDF Full-text (848 KB) | HTML Full-text | XML Full-text
Abstract
The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to
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The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV). We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95%) and low cytotoxicity (66% to 77%). Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy)-phenol (compound 1) and 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol (compound 2), which are classified as polybrominated diphenyl ethers (PBDEs), were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs. Full article
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Open AccessArticle The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity
Mar. Drugs 2015, 13(11), 6774-6791; doi:10.3390/md13116774
Received: 8 July 2015 / Revised: 27 October 2015 / Accepted: 2 November 2015 / Published: 9 November 2015
Cited by 2 | PDF Full-text (1206 KB) | HTML Full-text | XML Full-text
Abstract
Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte
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Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound. Full article
(This article belongs to the Special Issue Marine Anticoagulants and Antithrombotics)
Open AccessArticle Production of a Novel Fucoidanase for the Green Synthesis of Gold Nanoparticles by Streptomyces sp. and Its Cytotoxic Effect on HeLa Cells
Mar. Drugs 2015, 13(11), 6818-6837; doi:10.3390/md13116818
Received: 2 October 2015 / Revised: 3 November 2015 / Accepted: 3 November 2015 / Published: 12 November 2015
Cited by 6 | PDF Full-text (1690 KB) | HTML Full-text | XML Full-text
Abstract
Marine actinobacteria-produced fucoidanases have received considerable attention as one of the major research topics in recent years, particularly for the medical exploitation of fucoidans and their degradation products. The present study describes the optimization and production of a novel fucoidanase for the green
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Marine actinobacteria-produced fucoidanases have received considerable attention as one of the major research topics in recent years, particularly for the medical exploitation of fucoidans and their degradation products. The present study describes the optimization and production of a novel fucoidanase for the green synthesis of gold nanoparticles and its biological applications. The production of fucoidanase was optimized using Streptomyces sp. The medium components were selected in accordance with the Plackett-Burman design and were further optimized via response surface methodology. The fucoidanase was statistically optimized with the most significant factors, namely wheat bran 3.3441 g/L, kelp powder 0.7041 g/L, and NaCl 0.8807 g/L, respectively. The biosynthesized gold nanoparticles were determined by UV-vis spectroscopy and were further characterized by X-ray diffraction analysis, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray analysis, and high-resolution transmission electron microscopy. Furthermore, the biosynthesized gold nanoparticles exhibited a dose-dependent cytotoxicity against HeLa cells and the inhibitory concentration (IC50) was found to be 350 µg/mL at 24 h and 250 µg/mL at 48 h. Therefore, the production of novel fucoidanase for the green synthesis of gold nanoparticles has comparatively rapid, less expensive and wide application to anticancer therapy in modern medicine. Full article
(This article belongs to the Special Issue Green Chemistry Approach to Marine Products)
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Open AccessArticle Polyphenol-Rich Fraction of Ecklonia cava Improves Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Mice
Mar. Drugs 2015, 13(11), 6866-6883; doi:10.3390/md13116866
Received: 16 September 2015 / Revised: 28 October 2015 / Accepted: 30 October 2015 / Published: 12 November 2015
Cited by 6 | PDF Full-text (1785 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of
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Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1), the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism. Full article
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Open AccessArticle A New Analogue of Echinomycin and a New Cyclic Dipeptide from a Marine-Derived Streptomyces sp. LS298
Mar. Drugs 2015, 13(11), 6947-6961; doi:10.3390/md13116947
Received: 2 July 2015 / Revised: 5 November 2015 / Accepted: 6 November 2015 / Published: 18 November 2015
Cited by 2 | PDF Full-text (324 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were
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Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey’s method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
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Open AccessArticle Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells
Mar. Drugs 2015, 13(11), 6962-6976; doi:10.3390/md13116962
Received: 28 August 2015 / Accepted: 12 November 2015 / Published: 19 November 2015
Cited by 7 | PDF Full-text (1774 KB) | HTML Full-text | XML Full-text
Abstract
Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide
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Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents. Full article
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Open AccessArticle Phorbaketal A, Isolated from the Marine Sponge Phorbas sp., Exerts Its Anti-Inflammatory Effects via NF-κB Inhibition and Heme Oxygenase-1 Activation in Lipopolysaccharide-Stimulated Macrophages
Mar. Drugs 2015, 13(11), 7005-7019; doi:10.3390/md13117005
Received: 5 October 2015 / Accepted: 13 November 2015 / Published: 19 November 2015
Cited by 7 | PDF Full-text (503 KB) | HTML Full-text | XML Full-text
Abstract
Marine sponges harbor a range of biologically active compounds. Phorbaketal A is a tricyclic sesterterpenoid isolated from the marine sponge Phorbas sp.; however, little is known about its biological activities and associated molecular mechanisms. In this study, we examined the anti-inflammatory effects and
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Marine sponges harbor a range of biologically active compounds. Phorbaketal A is a tricyclic sesterterpenoid isolated from the marine sponge Phorbas sp.; however, little is known about its biological activities and associated molecular mechanisms. In this study, we examined the anti-inflammatory effects and underlying molecular mechanism of phorbaketal A in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that phorbaketal A significantly inhibited the LPS-induced production of nitric oxide (NO), but not prostaglandin E2, in RAW 264.7 cells. Further, phorbaketal A suppressed the expression of inducible NO synthase at both the mRNA and protein levels. In addition, phorbaketal A reduced the LPS-induced production of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein-1. Treatment with phorbaketal A inhibited the transcriptional activity of nuclear factor-kappaB (NF-κB), a crucial signaling molecule in inflammation. Moreover, phorbaketal A up-regulated the expression of heme oxygenase-1 (HO-1) in LPS-stimulated RAW 264.7 cells. These data suggest that phorbaketal A, isolated from the marine sponge Phorbas sp., inhibits the production of inflammatory mediators via down-regulation of the NF-κB pathway and up-regulation of the HO-1 pathway. Full article
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Open AccessArticle Interactions between Carotenoids from Marine Bacteria and Other Micronutrients: Impact on Stability and Antioxidant Activity
Mar. Drugs 2015, 13(11), 7020-7039; doi:10.3390/md13117020
Received: 6 August 2015 / Revised: 22 October 2015 / Accepted: 7 November 2015 / Published: 19 November 2015
Cited by 6 | PDF Full-text (1355 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recently isolated spore-forming pigmented marine bacteria Bacillus indicus HU36 are sources of oxygenated carotenoids with original structures (about fifteen distinct yellow and orange pigments with acylated d-glucosyl groups). In this study, we evaluated the stability (sensitivity to iron-induced autoxidation) and antioxidant activity (inhibition
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Recently isolated spore-forming pigmented marine bacteria Bacillus indicus HU36 are sources of oxygenated carotenoids with original structures (about fifteen distinct yellow and orange pigments with acylated d-glucosyl groups). In this study, we evaluated the stability (sensitivity to iron-induced autoxidation) and antioxidant activity (inhibition of iron-induced lipid peroxidation) of combinations of bacterial HU36 carotenoids with the bacterial vitamin menaquinone MQ-7 and with phenolic antioxidants (vitamin E, chlorogenic acid, rutin). Unexpectedly, MQ-7 strongly improves the ability of HU36 carotenoids to inhibit FeII-induced lipid peroxidation, although MQ-7 was not consumed in the medium. We propose that their interaction modifies the carotenoid antioxidant mechanism(s), possibly by allowing carotenoids to scavenge the initiating radicals. For comparison, β-carotene and lycopene in combination were shown to exhibit a slightly higher stability toward iron-induced autoxidation, as well as an additive antioxidant activity as compared to the carotenoids, individually. HU36 carotenoids and phenolic antioxidants displayed synergistic activities in the inhibition of linoleic acid peroxidation induced by heme iron, but not by free iron. Synergism could arise from antioxidants interacting via electron transfer through the porphyrin nucleus of heme iron. Overall, combining antioxidants acting via complementary mechanisms could be the key for optimizing the activity of this bacterial carotenoid cocktail. Full article
(This article belongs to the Special Issue Marine Lipids)
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Open AccessArticle Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones
Mar. Drugs 2015, 13(11), 7040-7054; doi:10.3390/md13117040
Received: 27 September 2015 / Accepted: 13 November 2015 / Published: 19 November 2015
Cited by 3 | PDF Full-text (1738 KB) | HTML Full-text | XML Full-text
Abstract
The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures
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The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids. Full article
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Open AccessReview Chitosanases from Family 46 of Glycoside Hydrolases: From Proteins to Phenotypes
Mar. Drugs 2015, 13(11), 6566-6587; doi:10.3390/md13116566
Received: 31 August 2015 / Revised: 9 October 2015 / Accepted: 13 October 2015 / Published: 28 October 2015
Cited by 6 | PDF Full-text (2141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC) or chitosan oligosaccharides (CHOS) from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46
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Chitosanases, enzymes that catalyze the endo-hydrolysis of glycolytic links in chitosan, are the subject of numerous studies as biotechnological tools to generate low molecular weight chitosan (LMWC) or chitosan oligosaccharides (CHOS) from native, high molecular weight chitosan. Glycoside hydrolases belonging to family GH46 are among the best-studied chitosanases, with four crystallography-derived structures available and more than forty enzymes studied at the biochemical level. They were also subjected to numerous site-directed mutagenesis studies, unraveling the molecular mechanisms of hydrolysis. This review is focused on the taxonomic distribution of GH46 proteins, their multi-modular character, the structure-function relationships and their biological functions in the host organisms. Full article
(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)
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Open AccessReview Fish Synucleins: An Update
Mar. Drugs 2015, 13(11), 6665-6686; doi:10.3390/md13116665
Received: 10 August 2015 / Accepted: 13 October 2015 / Published: 30 October 2015
Cited by 4 | PDF Full-text (1471 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies
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Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies have indicated that syn proteins are evolutionary conserved. No counterparts of syns were found in invertebrates suggesting that they are vertebrate-specific proteins. Molecular studies showed that the number of syn members varies among vertebrates. Three genes encode for α-, β- and γ-syn in mammals and birds. However, a variable number of syn genes and encoded proteins is expressed or predicted in fish depending on the species. Among biologically verified sequences, four syn genes were identified in fugu, encoding for α, β and two γ (γ1 and γ2) isoforms, whereas only three genes are expressed in zebrafish, which lacks α-syn gene. The list of “non verified” sequences is much longer and is often found in sequence databases. In this review we provide an overview of published papers and known syn sequences in agnathans and fish that are likely to impact future studies in this field. Indeed, fish models may play a key role in elucidating some of the molecular mechanisms involved in physiological and pathological functions of syn proteins. Full article
(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)
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Open AccessReview Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials
Mar. Drugs 2015, 13(11), 6792-6817; doi:10.3390/md13116792
Received: 5 October 2015 / Revised: 2 November 2015 / Accepted: 3 November 2015 / Published: 11 November 2015
Cited by 10 | PDF Full-text (2638 KB) | HTML Full-text | XML Full-text
Abstract
The substance secreted by mussels, also known as nature’s glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via
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The substance secreted by mussels, also known as nature’s glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via mussel adhesive proteins (MAPs), a group of proteins containing 3,4-dihydroxyphenylalanine (DOPA) and catecholic amino acid. Several aspects of this adhesion process have inspired the development of various types of synthetic materials for biomedical applications. Further, there is an urgent need to utilize biologically inspired strategies to develop new biocompatible materials for medical applications. Consequently, many researchers have recently reported bio-inspired techniques and materials that show results similar to or better than those shown by MAPs for a range of medical applications. However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion. In this review, various strategies are discussed to provide an option for DOPA/metal ion chelation and to compensate for the limitations imposed by facile 3,4-dihydroxyphenylalanine autoxidation. We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation. The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review. Full article
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Open AccessReview Seaweeds as Preventive Agents for Cardiovascular Diseases: From Nutrients to Functional Foods
Mar. Drugs 2015, 13(11), 6838-6865; doi:10.3390/md13116838
Received: 8 August 2015 / Revised: 16 October 2015 / Accepted: 30 October 2015 / Published: 12 November 2015
Cited by 10 | PDF Full-text (298 KB) | HTML Full-text | XML Full-text
Abstract
Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, phlorotannins, lipids and minerals are macroalgae’s major compounds that can hold potential in high-value food products derived from
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Being naturally enriched in key nutrients and in various health-promoting compounds, seaweeds represent promising candidates for the design of functional foods. Soluble dietary fibers, peptides, phlorotannins, lipids and minerals are macroalgae’s major compounds that can hold potential in high-value food products derived from macroalgae, including those directed to the cardiovascular-health promotion. This manuscript revises available reported data focusing the role of diet supplementation of macroalgae, or extracts enriched in bioactive compounds from macroalgae origin, in targeting modifiable markers of cardiovascular diseases (CVDs), like dyslipidemia, oxidative stress, vascular inflammation, hypertension, hypercoagulability and activation of the sympathetic and renin-angiotensin systems, among others. At last, the review also describes several products that have been formulated with the use of whole macroalgae or extracts, along with their claimed cardiovascular-associated benefits. Full article
(This article belongs to the Special Issue Marine Functional Food)
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Open AccessReview Marine Drugs Regulating Apoptosis Induced by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)
Mar. Drugs 2015, 13(11), 6884-6909; doi:10.3390/md13116884
Received: 21 September 2015 / Revised: 2 November 2015 / Accepted: 9 November 2015 / Published: 13 November 2015
Cited by 6 | PDF Full-text (1540 KB) | HTML Full-text | XML Full-text
Abstract
Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells
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Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells. Full article
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Open AccessReview Cyanobactins from Cyanobacteria: Current Genetic and Chemical State of Knowledge
Mar. Drugs 2015, 13(11), 6910-6946; doi:10.3390/md13116910
Received: 25 June 2015 / Revised: 22 September 2015 / Accepted: 30 October 2015 / Published: 13 November 2015
Cited by 9 | PDF Full-text (4089 KB) | HTML Full-text | XML Full-text
Abstract
Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins
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Cyanobacteria are considered to be one of the most promising sources of new, natural products. Apart from non-ribosomal peptides and polyketides, ribosomally synthesized and post-translationally modified peptides (RiPPs) are one of the leading groups of bioactive compounds produced by cyanobacteria. Among these, cyanobactins have sparked attention due to their interesting bioactivities and for their potential to be prospective candidates in the development of drugs. It is assumed that the primary source of cyanobactins is cyanobacteria, although these compounds have also been isolated from marine animals such as ascidians, sponges and mollusks. The aim of this review is to update the current knowledge of cyanobactins, recognized as being produced by cyanobacteria, and to emphasize their genetic clusters and chemical structures as well as their bioactivities, ecological roles and biotechnological potential. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Open AccessReview Omega-3 Fatty Acids and Skeletal Muscle Health
Mar. Drugs 2015, 13(11), 6977-7004; doi:10.3390/md13116977
Received: 5 October 2015 / Revised: 30 October 2015 / Accepted: 9 November 2015 / Published: 19 November 2015
Cited by 13 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on
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Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. Full article
(This article belongs to the Special Issue Marine Fatty Acids-2016)
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