Xuan Zhang

Four new metabolites, including two resorcinol derivatives, (S)-1-(2,4-dihydroxy-3,5-dimethylphenyl)-3-hydroxybutan-1-one (1) and 5-[(8S)-2-hydroxypropyl]-6-methylbenzene-1,3-diol (2), a benzo[c][1,2]dioxine derivative, (S)-3,5,7-trimethyl-3,4-dihydrobenzo[c][1,2]dioxine-6,8-diol (3), and a cytochalasan alkaloid, 7-O-acetylarmochaetoglobin Q (5), along with nine known compounds, were isolated from the marine fungus Chaetomium globosum F0831, obtained from a South China Sea marine sediment. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations (Electronic Circular Dichroism calculations). The anti-inflammatory activity of the isolated compounds was evaluated. Compound 8 was discovered to potentially reduce inflammation through suppression of the AKT/STAT3 pathway, thereby inhibiting the release of inflammatory mediators (iNOS, COX-2) and inflammatory cytokines (IL-6, TNF-α, and IL-1β).

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.