Marine Drugs — Open Access Journal

Platelet-rich plasma (PRP) is rich in growth factors and has commonly been utilized in the repair and regeneration of damaged articular cartilage. However, the major drawbacks of direct PRP injection are unstable biological fixation and fast or burst release of growth factors. Fucoidan is a heparinoid compound that can bind growth factors to control their release rate. Furthermore, fucoidan can reduce arthritis through suppressing inflammatory responses and thus it has been reported to prevent the progression of osteoarthritis, promote bone regeneration and accelerate healing of cartilage injury. Injectable hydrogels can be used to deliver cells and growth factors for an alternative, less invasive treatment of cartilage defects. In this study, hyaluronic acid (HA) and fucoidan (FD) was blended with gelatin (GLT) and the GLT/HA/FD hybrid was further cross-linked with genipin (GP) to prepare injectable GP-GLT/HA/FD hydrogels. The gelation rate was affected by the GP, GLT, HA and FD concentrations, as well as the pH values. The addition of HA and FD to GLT networks improved the mechanical strength of the hydrogels and facilitated the sustained release of PRP growth factors. The GP-GLT/HA/FD hydrogel showed adequate injectability, shape-persistent property and strong adhesive ability, and was more resistant to enzymatic degradation. The PRP-loaded GP-GLT/HA/FD hydrogel promoted cartilage regeneration in rabbits, which may lead to an advanced PRP therapy for enhancing cartilage repair. Full article

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway. Full article

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H₂O₂- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress. Full article

Recent studies have clearly shown the importance of omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) for human and animal health. The long-chain eicosapentaenoic acid (EPA; 20:5ω-3) and docosahexaenoic acid (DHA; 22:6ω-3) are especially recognized for their nutritional value, and ability to alleviate many diseases in humans. So far, fish oil has been the main human source of EPA and DHA, but alternative sources are needed to satisfy the growing need for them. Therefore, we compared a fatty acid profile and content of 10 diatoms and seven dinoflagellates originating from marine, brackish and freshwater habitats. These two phytoplankton groups were chosen since they are excellent producers of EPA and DHA in aquatic food webs. Multivariate analysis revealed that, whereas the phytoplankton group (46%) explained most of the differences in the fatty acid profiles, habitat (31%) together with phytoplankton group (24%) explained differences in the fatty acid contents. In both diatoms and dinoflagellates, the total fatty acid concentrations and the ω-3 and ω-6 PUFAs were markedly higher in freshwater than in brackish or marine strains. Our results show that, even though the fatty acid profiles are genetically ordered, the fatty acid contents may vary greatly by habitat and affect the ω-3 and ω-6 availability in food webs. Full article

Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant S. aureus and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications. Full article

Mangroves are ecologically important plants in marine habitats that occupy the coastlines of many countries. In addition to their key ecological importance, various parts of mangroves are widely used in folklore medicine and claimed to effectively manage a panoply of human pathologies. To date, no comprehensive attempt has been made to compile and critically analyze the published literature in light of its ethnopharmacological uses. This review aims to provide a comprehensive account of the morphological characteristics, ethnobotany, global distribution, taxonomy, ethnopharmacology, phytochemical profiles, and pharmacological activities of traditionally used mangroves. Out of 84 mangrove species, only 27 species were found to be traditionally used, however not all of them are pharmacologically validated. The most common pharmacological activities reported were antioxidant, antimicrobial, and antidiabetic properties. Mangroves traditionally reported against ulcers have not been extensively validated for possible pharmacological properties. Terpenoids, tannins, steroids, alkaloids, flavonoids, and saponins were the main classes of phytochemicals isolated from mangroves. Given that mangroves have huge potential for a wide array of medicinal products and drug discovery to prevent and treat many diseases, there is a dire need for careful investigations substantiated with accurate scientific and clinical evidence to ensure safety and efficient use of these plants and validate their pharmacological properties and toxicity. Full article

The subtidal red alga Plocamium cartilagineum was collected from the Western Antarctic Peninsula during the 2011 and 2017 austral summers. Bulk collections from specific sites corresponded to chemogroups identified by Young et al. in 2013. One of the chemogroups yielded several known acyclic halogenated monoterpenes (2–5) as well as undescribed compounds of the same class, anverenes B–D (6–8). Examination of another chemogroup yielded an undescribed cyclic halogenated monoterpene anverene E (9) as its major secondary metabolite. Elucidation of structures was achieved through one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) spectroscopy and negative chemical ionization mass spectrometry. Compounds 1–9 show moderate cytotoxicity against cervical cancer (HeLa) cells. Full article

Marine organisms, particularly cyanobacteria, are important resources for the production of bioactive secondary metabolites for the treatment of human diseases. In this study, a bioassay-guided approach was used to discover metabolites with lipid-reducing activity. Two chlorophyll derivatives were successfully isolated, the previously described 13²-hydroxy-pheophytin a (1) and the new compound 13²-hydroxy-pheofarnesin a (2). The structure elucidation of the new compound 2 was established based on one- and two-dimensional (1D and 2D) NMR spectroscopy and mass spectrometry. Compounds 1 and 2 showed significant neutral lipid-reducing activity in the zebrafish Nile red fat metabolism assay after 48 h of exposure with a half maximal effective concentration (EC₅₀) of 8.9 ± 0.4 µM for 1 and 15.5 ± 1.3 µM for 2. Both compounds additionally reduced neutral lipid accumulation in 3T3-L1 multicellular spheroids of murine preadipocytes. Molecular profiling of mRNA expression of some target genes was evaluated for the higher potent compound 1, which indicated altered peroxisome proliferator activated receptor gamma (PPARγ) mRNA expression. Lipolysis was not affected. Different food materials (Spirulina, Chlorella, spinach, and cabbage) were evaluated for the presence of 1, and the cyanobacterium Spirulina, with GRAS (generally regarded as safe) status for human consumption, contained high amounts of 1. In summary, known and novel chlorophyll derivatives were discovered from marine cyanobacteria with relevant lipid-reducing activities, which in the future may be developed into nutraceuticals. Full article

Marine sponges are a prolific source of bioactive compounds. In this work, the putative antiangiogenic potential of a series of synthetic precursors of Solomonamide A, a cyclic peptide isolated from a marine sponge, was evaluated. By means of an in vitroscreening, based on the inhibitory activity of endothelial tube formation, the compound Solo F–OH was selected for a deeper characterization of its antiangiogenic potential. Our results indicate that Solo F–OH is able to inhibit some key steps of the angiogenic process, including the proliferation, migration, and invasion of endothelial cells, as well as diminish their capability to degrade the extracellular matrix proteins. The antiangiogenic potential of Solo F–OH was confirmed by means of two different in vivo models: the chorioallantoic membrane (CAM) and the zebrafish yolk membrane (ZFYM) assays. The reduction in ERK1/2 and Akt phosphorylation in endothelial cells treated with Solo F–OH denotes that this compound could target the upstream components that are common to both pathways. Taken together, our results show a new and interesting biological activity of Solo F–OH as an inhibitor of the persistent and deregulated angiogenesis that characterizes cancer and other pathologies. Full article

In the study, the protective effect of plasma protein from Tachypleus tridentatus (PPTT) on acute kidney injury (AKI) and the related molecular mechanisms were first investigated by Western blotting analyses, TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, and immunohistochemistry. It was found that PPTT had an obviously inhibitory effect on Reactive oxygen species (ROS) in cyclophosphamide (CTX)-exposed mice. Furthermore, results demonstrated that the renal cell death mode is due to inducing apoptosis and autophagy inhibited by dose-dependent PPTT in mice treated with CTX by decreasing the protein expression of bax, beclin-1, and LC3 and increasing the expression of bcl-2. Moreover, the p38 MAPK and PI3K/Akt signaling pathways were observed to take part in the PPTT-induced renal cell growth effect by enhancing the upregulation of the expression of Akt and p-Akt as well as the downregulation of the expression of p38 and p-p38, which indicated a PPTT ameliorating effect on AKI CTX-induced in mice through p38 MAPK and PI3K/Akt signaling pathways. Briefly, this article preliminarily studies the mechanism of the PPTT ameliorating effect on AKI CTX-induced in mice, which helps to provide a reference for PPTT clinical application in AKI therapy. Full article

The first total synthesis of the marine nucleoside Mycalisine B—a naturally occurring and structurally distinct 4,5-unsaturated 7-deazapurine nucleoside—has been accomplished in 10 linear steps with 27.5% overall yield from commercially available 1,2,3,5-tetra-O-acetyl-ribose and tetracyanoethylene. Key steps of the approach include: (1) I₂ catalyzed acetonide formation from 1,2,3,5-tetra-O-acetylribose and acetone at large scale; (2) Vorbrüggen glycosylation using N⁴-benzoyl-5-cyano-6-bromo-7H-pyrrolo[2,3–d]pyrimidine as a nucleobase to avoid formation of N-3 isomer; (3) mild and scalable reaction conditions. Full article

Phloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with oxidative stress (hydrogen peroxide, H₂O₂). The results showed that PG significantly inhibited the H₂O₂-induced growth inhibition in HaCaT cells, which was associated with increased expression of heme oxygenase-1 (HO-1) by the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PG remarkably reversed H₂O₂-induced excessive ROS production, DNA damage, and apoptosis. Additionally, H₂O₂-induced mitochondrial dysfunction was related to a decrease in ATP levels, and in the presence of PG, these changes were significantly impaired. Furthermore, the increases of cytosolic release of cytochrome c and ratio of Bax to Bcl-2, and the activation of caspase-9 and caspase-3 by the H₂O₂ were markedly abolished under the condition of PG pretreatment. However, the inhibition of HO-1 function using zinc protoporphyrin, a HO-1 inhibitor, markedly attenuated these protective effects of PG against H₂O₂. Overall, our results suggest that PG is able to protect HaCaT keratinocytes against oxidative stress-induced DNA damage and apoptosis through activating the Nrf2/HO-1 signaling pathway. Full article

A previous report indicated that collagen hydrolysate fraction (F7) from Spanish mackerel (Scomberomorous niphonius) skins showed high reducing power and radical scavenging activities on 2,2-Diphenyl-1-picrylhydrazyl (DPPH) (EC₅₀ value of 1.57 mg/mL) and hydroxyl (EC₅₀ value of 1.20 mg/mL). In this work, eight peptides were isolated from F7 and identified as Gly-Pro-Tyr (GPY, 335.31 Da), Gly-Pro-Thr-Gly-Glu (GPTGE, 459.47 Da), Pro-Phe-Gly-Pro-Asp (PFGPD, 531.52 Da), Gly-Pro-Thr-Gly-Ala-Lys (GPTGAKG, 586.65 Da), Pro-Tyr-Gly-Ala-Lys-Gly (PYGAKG, 591.69 Da), Gly-Ala-Thr-Gly-Pro-Gln-Gly (GATGPQG, 586.61 Da), Gly-Pro-Phe-Gly-Pro-Met (GPFGPM, 604.73 Da), and Tyr-Gly-Pro-Met (YGPM, 466.50 Da), respectively. Among them, PFGPD, PYGAKG, and YGPM exhibited strong radical scavenging activities on DPPH (EC₅₀ values of 0.80, 3.02, and 0.72 mg/mL for PFGPD, PYGAKG, and YGPM, respectively), hydroxyl (EC₅₀ values of 0.81, 0.66, and 0.88 mg/mL for PFGPD, PYGAKG, and YGPM, respectively), superoxide anion (EC₅₀ values of 0.91, 0.80, and 0.73 mg/mL for PFGPD, PYGAKG, and YGPM, respectively), and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) cation (EC₅₀ values of 0.86, 1.07, and 0.82 mg/mL for PFGPD, PYGAKG, and YGPM, respectively) in a positive concentration–activity relationship. Furthermore, PFGPD, PYGAKG, and YGPM could effectively reduce Fe³⁺ to Fe²⁺ and inhibit lipid peroxidation. Hence, eight collagen peptides from hydrolysate of Spanish mackerel skins might be served as antioxidant candidates for various industrial applications. Full article

The composition and properties of collagen in teleost (bony fish) cartilage have never been studied. In this study, we aimed to identify and characterise all collagen species in the nasal cartilage of hoki (Macruronus novaezelandiae). Four native collagen species were extracted using two techniques, and isolated with differential salt precipitation. We were able to assign the identity of three of these collagen species on the basis of solubility, SDS-PAGE and amino acid analyses. We found that hoki cartilage contains the major collagen, type II, and the minor collagens, type IX and type XI, which are homologous to those found in mammal and chicken cartilage. Using these extraction protocols, we also isolated a full-length type IX collagen from cartilage for the first time. In addition, we detected a 90 kDa, highly glycosylated collagen that has not been identified in any other species. For each isolate, structural and biochemical characterisations were performed using circular dichroism and Fourier transform infrared spectroscopy analyses, and the thermal denaturation properties were determined. Our results showed that the properties of hoki cartilage-derived collagens are similar to those of collagens in mammalian cartilage, indicating that teleost cartilage could provide biological ingredients for the development of biomaterials to treat cartilage-related illnesses. Full article

Prolonged exposure to ultraviolet (UV) radiation causes photoaging of the skin and induces a number of disorders, including sunburn, fine and coarse wrinkles, and skin cancer risk. Therefore, the application of sunscreen has gained much attention to reduce the harmful effects of UV irradiation on our skin. Recently, there has been a growing demand for the replacement of chemical sunscreens with natural UV-absorbing compounds. Mycosporine-like amino acids (MAAs), promising alternative natural UV-absorbing compounds, are a group of widely distributed, low molecular-weight, water-soluble molecules that can absorb UV radiation and disperse the absorbed energy as heat, without generating reactive oxygen species (ROS). More than 30 MAAs have been characterized, from a variety of organisms. In addition to their UV-absorbing properties, there is substantial evidence that MAAs have the potential to protect against skin aging, including antioxidative activity, anti-inflammatory activity, inhibition of protein-glycation, and inhibition of collagenase activity. This review will provide an overview of MAAs, as potential anti-aging ingredients, beginning with their structure, before moving on to discuss the most recent experimental observations, including the molecular and cellular mechanisms through which MAAs might protect the skin. In particular, we focus on the potential anti-aging activity of mycosporine-2-glycine (M2G). Full article

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to the motor dysfunctions of patients. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progress was revealed to be associated with the abnormal aggregation of α-synuclein, the elevation of oxidative stress, the dysfunction of mitochondrial functions, and the increase of neuroinflammation. However, current anti-PD therapies could only produce symptom-relieving effects, because they could not provide neuroprotective effects, stop or delay the degeneration of dopaminergic neurons. Marine-derived natural compounds, with their novel chemical structures and unique biological activities, may provide anti-PD neuroprotective effects. In this study, we have summarized anti-PD marine-derived natural products which have shown pharmacological activities by acting on various PD targets, such as α-synuclein, monoamine oxidase B, and reactive oxygen species. Moreover, marine-derived natural compounds currently evaluated in the clinical trials for the treatment of PD are also discussed. Full article

The emergence of antibiotic resistance and viruses with high epidemic potential made unexplored marine environments an appealing target source for new metabolites. Marine fungi represent one of the most suitable sources for the discovery of new compounds. Thus, the aim of this work was (i) to isolate and identify fungi associated with the Atlantic sponge Grantia compressa; (ii) to study the fungal metabolites by applying the OSMAC approach (one strain; many compounds); (iii) to test fungal compounds for their antimicrobial activities. Twenty-one fungal strains (17 taxa) were isolated from G. compressa. The OSMAC approach revealed an astonishing metabolic diversity in the marine fungus Eurotium chevalieri MUT 2316, from which 10 compounds were extracted, isolated, and characterized. All metabolites were tested against viruses and bacteria (reference and multidrug-resistant strains). Dihydroauroglaucin completely inhibited the replication of influenza A virus; as for herpes simplex virus 1, total inhibition of replication was observed for both physcion and neoechinulin D. Six out of 10 compounds were active against Gram-positive bacteria with isodihydroauroglaucin being the most promising compound (minimal inhibitory concentration (MIC) 4–64 µg/mL) with bactericidal activity. Overall, G. compressa proved to be an outstanding source of fungal diversity. Marine fungi were capable of producing different metabolites; in particular, the compounds isolated from E. chevalieri showed promising bioactivity against well-known and emerging pathogens. Full article

Four new ansamycins, named divergolides T–W (1–4), along with two known analogs were isolated from the fermentation broth of the mangrove-derived actinomycete Streptomyces sp. KFD18. The structures of the compounds, including the absolute configurations of their stereogenic carbons, were determined by spectroscopic data and single-crystal X-ray diffraction analysis. Compounds 1–4 showed cytotoxic activity against the human gastric cancer cell line SGC-7901, the human leukemic cell line K562, the HeLa cell line, and the human lung carcinoma cell line A549, with 1 being the most active while compounds 5 and 6 were inactive against all the tested cell lines. Compounds 1 and 3 showed very potent and specific cytotoxic activities (IC₅₀ 2.8 and 4.7 µM, respectively) against the SGC-7901 cells. Further, the apoptosis-inducing effect of 1 and 3 against SGC-7901 cells was demonstrated by two kinds of staining methods for the first time. Full article

In order to find out the seeds of antitumor agents, we focused on potential bioactive materials from marine-derived microorganisms. Marine products include a number of compounds with unique structures, some of which may exhibit unusual bioactivities. As a part of this study, we studied metabolites of a strain of Alternaria sp. OUPS-117D-1 originally derived from the sea urchin Anthocidaris crassispina, and isolated five new decalin derivatives, altercrasins A–E (1–5). The absolute stereostructure of altercrasins A (1) had been decided by chemical transformation and the modified Mosher’s method. In this study, four decalin derivatives, altercrasins B–E (2–5) were purified by silica gel chromatography, and reversed phase high-performance liquid chromatography (RP HPLC), and their structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic analyses. The absolute configuration of them were deduced by the comparison with 1 in the NMR chemical shifts, NOESY correlations, and electronic circular dichroism (ECD) spectral analyses. As a result, we found out that compound pairs of 1/2 and 4/5 were respective stereoisomers. In addition, their cytotoxic activities using murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines showed that 4 and 5 exhibit potent cytotoxicity, in especially, the activity of 4 was equal to that of 5-fluorouracil. Full article