Mar. Drugs2015, 13(7), 4156-4170; doi:10.3390/md13074156 - published 30 June 2015 Show/Hide Abstract
Abstract: Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05) and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05). Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05). MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05). Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01). Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.
Mar. Drugs2015, 13(7), 4137-4155; doi:10.3390/md13074137 - published 30 June 2015 Show/Hide Abstract
Abstract: Marine fungi are potential producers of bioactive compounds that may have pharmacological and medicinal applications. Fungi were cultured from marine brown algae and identified using multiple target genes to confirm phylogenetic placement. These target genes included the internal transcribed spacer (ITS), the nuclear large subunit (LSU), and the β-tubulin region. Various biological activities of marine-derived fungi were evaluated, including their antifungal, antioxidant and cellulolytic enzyme activities. As a result, a total of 50 fungi was isolated from the brown algae Sargassum sp. Among the 50 isolated fungi, Corollospora angusta was the dominant species in this study. The genus Arthrinium showed a relatively strong antifungal activity to all of the target plant pathogenic fungi. In particular, Arthrinium saccharicola KUC21221 showed high radical scavenging activity and the highest activities in terms of filter paper units (0.39 U/mL), endoglucanase activity (0.38 U/mL), and β-glucosidase activity (1.04 U/mL).
Mar. Drugs2015, 13(7), 4044-4136; doi:10.3390/md13074044 - published 30 June 2015 Show/Hide Abstract
Abstract: This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.
Mar. Drugs2015, 13(7), 4006-4043; doi:10.3390/md13074006 - published 29 June 2015 Show/Hide Abstract
Abstract: Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.
Mar. Drugs2015, 13(7), 3992-4005; doi:10.3390/md13073992 - published 24 June 2015 Show/Hide Abstract
Abstract: Increased interest in marine resources has led to increased screening of marine fungi for novel bioactive compounds and considerable effort is being invested in discovering these metabolites. For compound discovery, small-scale cultures are adequate, but agitated bioreactors are desirable for larger-scale production. Calcarisporium sp. KF525 has recently been described to produce calcaride A, a cyclic polyester with antibiotic activity, in agitated flasks. Here, we describe improvements in the production of calcaride A in both flasks (13-fold improvement) and stirred bioreactors (200-fold improvement). Production of calcaride A in bioreactors was initially substantially lower than in shaken flasks. The cultivation pH (reduced from 6.8 to <5.4), carbon source (sucrose replacing glucose), C/N ratio and nature of mycelial growth (pellets or filaments) were important in improving calcaride A production. Up to 4.5 mg·g−1 biomass (85 mg·L−1) calcaride A were produced in the bioreactor, which was only slightly less than in shaken flasks (14 mg·g−1, 100 mg·L−1). The results demonstrate that a scalable process for calcaride A production could be developed using an iterative approach with flasks and bioreactors.
Mar. Drugs2015, 13(6), 3950-3991; doi:10.3390/md13063950 - published 19 June 2015 Show/Hide Abstract
Abstract: Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.