Marine Drugs

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa, and there is currently a lack of safe and effective treatment drugs. Resorcylic acid lactones (RALs) are a natural product that have been reported to have anti-inflammatory effects. However, the mechanism of whether RALs can treat UC and their anti-inflammatory effects remains underexplored. In this study, three new RAL derivatives, Penicillactones A–C (1–3), along with seven known analogs (4–10), were isolated from the marine fungus Penicillium sp. HN20. The structures of compounds 1–3 were elucidated by spectroscopic methods, ¹³C NMR theoretical calculations, and ECD analysis. Among these, compound 4 exhibited potent anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages. In a dextran sulfate sodium (DSS)-induced UC model, compound 4 alleviated body weight loss, disease activity, colon shortening, and spleen enlargement, and protected intestinal epithelial integrity. Mechanistic studies revealed that compound 4 primarily exerts its effects by downregulating the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling pathway, inhibiting pro-inflammatory cytokine production. Collectively, these findings provide the first evidence that marine-derived RAL derivatives exert anti-inflammatory effects by inhibiting the MAPK/ERK pathway, highlighting compound 4 as a promising therapeutic candidate for inflammation and UC.

This study explores the taxonomic diversity, metabolic profile, and bioactivity of marine-derived actinomycetes isolated from sediments collected off the coast of Lisbon and Setúbal Peninsula, Portugal. The combined use of two sediment pre-treatments (heat shock and dry overnight) and four growth media with varying nutrient concentrations revealed that formulations 10% A1 and SWA were most effective for recovering diverse actinomycetes, including rare Actinomadura, resulting in a total of 142 cultivable strains closely related to 47 phylogenetic distinct species dominated by Streptomyces and Micromonospora. Antimicrobial screening against methicillin-resistant Staphylococcus aureus (MRSA, COL) and Escherichia coli (K12) identified 22 bioactive strains, with strain PTS-083 exhibiting the strongest activity against MRSA (MIC = 1.95 µg/mL) and a 98.30% 16S rRNA gene identity to S. chumphonensis, highlighting it as a strong candidate for further metabolite and genomic studies. Cytotoxicity assays against HCT-116 human colorectal adenocarcinoma cells revealed eight bioactive strains with potent anticancer activity for extracts from strains related to S. sundarbansensis, S. violaceorubidus, and S. aculeolatus (IC₅₀ < 0.005–5.08 µg/mL). Untargeted LC-MS/MS metabolomic analysis uncovered a wide array of secondary metabolites, including macrolides, siderophores, fatty acids, and cyclic peptides. Comparative analyses with other Portuguese coastal studies revealed both shared and distinctive metabolomic profiles, emphasizing the importance of exhaustive sampling, even at nearby locations, as their localized environmental conditions can influence metabolic diversity. These findings highlight Portugal’s coastal sediments as a rich and underexplored source of novel actinomycetes and bioactive compounds with promising pharmaceutical applications. Exhaustive sampling of marine sediment actinomycete communities, even at nearby locations, is crucial for discovering unique metabolites with potential biotechnological value.

In France, as part of the monitoring program for the emergence of marine toxins in shellfish (EMERGTOX), brevetoxins (BTX-2, BTX-3) were first detected in shellfish from Corsica (Mediterranean Sea) in 2018. The complex metabolic transformation of brevetoxins in shellfish, coupled with the limited availability of analytical standards for most metabolites, complicates the accurate evaluation of contamination levels. To address this challenge, two complementary analytical approaches were implemented to quantify brevetoxin metabolites in shellfish samples collected from 2018 to 2023: (i) a targeted LC-MS/MS method specially developed for brevetoxins; and (ii) an ELISA capable of detecting metabolites for which no reference standards are available. Of the 11 brevetoxin metabolites targeted, 4 were quantified by LC-MS/MS: BTX-2, BTX-3, BTX-B5, and S-deoxy-BTX-B2 (including its isomers). The ELISA consistently detected brevetoxins in all Corsican samples previously confirmed positive by LC-MS/MS, with concentrations systematically exceeding those measured by LC-MS/MS. This overestimation may result from antibody cross-reactivity and from the presence of unidentified brevetoxin metabolites not detected by LC-MS/MS. Regardless of the analytical method used, the highest concentration detected exceeded the current French guideline value for brevetoxins in shellfish. To ensure consumer protection, a two-step monitoring strategy is proposed: initial screening via ELISA to estimate brevetoxin contamination, followed by confirmatory LC-MS/MS analysis to identify and quantify the specific metabolites.