Marine Drugs最新文献

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins (7-9), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (1) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (1) and (-)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis. These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites.

Ishige okamurae (I. okamuare), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of intracellular MGO/MGO-derived advanced glycation end products (AGE), and regulation of downstream signaling pathways related to the AGE-receptor for AGEs (RAGE) interaction. IPA (0.2, 1, and 5 μM) demonstrated anti-glycation ability by inhibiting the formation of glucose-fructose-BSA-derived AGEs by up to 54.63% compared to the untreated control, reducing the formation of irreversible cross-links between MGO-derived AGEs and collagen by 67.68% and the breaking down of existing cross-links by approximately 91% (p < 0.001). IPA protected cells from MGO-induced oxidative stress by inhibiting intracellular MGO accumulation (untreated cells: 1.62 μg/mL, MGO treated cells: 25.27 μg/mL, and IPA 5 μM: 11.23 μg/mL) (p < 0.001) and AGE generation and inhibited MGO-induced renal cell damage via the downregulation of MGO-induced RAGE protein expression (relative protein expression levels of MGO treated cells: 9.37 and IPA 5 μM:1.74) (p < 0.001). Overall, these results suggest that IPA has the potential to be utilized as a useful natural agent for the prevention and management of AGE-related diabetic nephropathy, owing to its strong anti-glycation activity.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development. In this study, we isolated 44 natural products from deep-sea-derived fungi and identified isobisvertinol (17) as a compound with anti-inflammatory and ferroptosis-inhibiting effects. Using LPS-induced microglial inflammation and RSL3-induced neuronal ferroptosis models, we found that 17 targets TLR4 to provide neuroprotection. Molecular docking studies revealed that 17 inhibits TLR4 activation by occupying the hydrophobic pocket at the TLR4-MD2 binding site. Additionally, 17 suppresses TLR4, reducing p38 MAPK phosphorylation, and inhibits ferroptosis by decreasing lipid peroxidation and modulating mitochondrial membrane potential. Metabolomic analysis showed that 17 rescues alterations in multiple metabolic pathways induced by RSL3 and increases levels of antioxidant metabolites, including glutamine, glutamate, and glutathione. In summary, our results indicate that isobisvertinol (17) targets TLR4 in neural cells to reduce inflammation and inhibit p38 MAPK phosphorylation, while regulating metabolic pathways, mainly GSH synthesis, to provide antioxidant effects and prevent ferroptosis in neurons.

Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine organisms, especially in IBD, using a zebrafish model. The results indicated that MBD could inhibit the inflammatory responses induced by CuSO₄, tail amputation and LPS in zebrafish. Furthermore, MBD notably inhibited the intestinal migration of immune cells, enhanced the integrity of the gut mucosal barrier and improved intestinal peristalsis function in a zebrafish IBD model induced by trinitro-benzene-sulfonic acid (TNBS). In addition, MBD could inhibit ROS elevation induced by TNBS. Network pharmacology analysis, molecular docking, transcriptomics sequencing and RT-PCR were conducted to investigate the potential mechanism. The results showed that MBD could regulate the TLR/NF-κB pathways by inhibiting the mRNA expression of TNF-α, NF-κB, IL-1, IL-1β, IL6, AP1, IFNγ, IKKβ, MyD88, STAT3, TRAF1, TRAF6, NLRP3, NOD2, TLR3 and TLR4, and promoting the mRNA expression of IL4, IκBα and Bcl-2. In conclusion, these findings indicate that MBD could be a potential candidate for the treatment of IBD.

A rise in antimicrobial resistance coupled with consumer preferences towards natural preservatives has resulted in increased research towards investigating antimicrobial compounds from natural sources such as macroalgae (seaweeds), which contain antioxidant, antimicrobial, and anticancer compounds. This study investigates the antimicrobial activity of compounds produced by the Irish seaweed Alaria esculenta against Escherichia coli and Listeria innocua, bacterial species which are relevant for food safety. Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), ultrasound-microwave-assisted extraction (UMAE), and conventional extraction technologies (maceration) were applied to generate extracts from A. esculenta, followed by their preliminary chemical composition (total phenolic content, total protein content, total soluble sugars) and antimicrobial activity (with minimum inhibitory concentration determined by broth microdilution methods), examining also the molecular weight distribution (via high performance size exclusion chromatography) and oligosaccharide fraction composition (via high-performance liquid chromatography) of the polysaccharides, as they were the predominant compounds in these extracts, aiming to elucidate structure-function relationships. The chemical composition of the extracts demonstrated that they were high in total soluble sugars, with the highest total sugars being seen from the extract prepared with UAE, having 32.68 mg glucose equivalents/100 mg dried extract. Extracts had antimicrobial activity against E. coli and featured minimum inhibitory concentration (MIC) values of 6.25 mg/mL (in the case of the extract prepared with UAE) and 12.5 mg/mL (in the case of the extracts prepared with MAE, UMAE, and conventional maceration). No antimicrobial activity was seen by any extracts against L. innocua. An analysis of molar mass distribution of A. esculenta extracts showed high heterogeneity, with high-molecular-weight areas possibly indicating the presence of fucoidan. The FTIR spectra also indicated the presence of fucoidan as well as alginate, both of which are commonly found in brown seaweeds. These results indicate the potential of antimicrobials from seaweeds extracted using green technologies.

New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, we report 12 unreported cadinene-like functionalized sesquiterpenes, anthoteibinenes F-Q. The metabolites were isolated using both bioassay- and ¹H NMR-guided approaches. One-/two-dimensional NMR spectroscopy and high-resolution mass spectrometry were used for structure elucidation, while a combination of NOESY NMR experiments, GIAO NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose relative and absolute configurations of the anthoteibinenes. The metabolites were screened against the Respiratory Syncytial Virus (RSV), ESKAPE pathogens, five Candida albicans strains, and one strain of C. auris.

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC₅₀ = 12.47 and 18 µg/mL) and HepG2 (IC₅₀ = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications.

Ciguatera poisoning (CP) is caused by the consumption of marine products contaminated with ciguatoxins (CTXs) produced by dinoflagellates of the genus Gambierdiscus. Analytical methods for CTXs, involving the extraction/purification of trace quantities of CTXs from complex matrices, are numerous in the literature. However, little information on their effectiveness for nonpolar CTXs is available, yet these congeners, contributing to the risk of CP, are required for the establishment of effective food safety monitoring programs. An evaluation of six extraction/purification protocols, performed with CTX3C spiked on fish flesh and a neuroblastoma cell-based assay (CBA-N2a), revealed recoveries from 6 to 45%. This led to the development of an optimized 3-day protocol designed for a large number of samples, with CTX1B and CTX3C eluting in a single fraction and showing recoveries of 73% and 70%, respectively. In addition, a reduction in adverse matrix effects in the CBA-N2a analyses was demonstrated with naturally contaminated specimens, increasing the sensitivity of the method, which now meets the very low guidance level recommended by international agencies. However, efforts are still required to reduce the signal suppression observed in LC-MS/MS analysis. This optimized protocol contributes to the technological advancement of detection methods, promoting food safety and improving CP risk assessment in marine products.

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents.

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase.