Curtachalasins Y1-Y13, Anti-Inflammatory Cytochalasans from the Soil Fungus Xylaria sp. Y01

Twenty-seven cytochalasans, including thirteen previously undescribed analogs with a 5/6/6/6 tetracyclic skeleton (curtachalasins Y1-Y13), were isolated from the rice-based culture of a soil-derived fungus, Xylaria sp. Y01. Their structures were determined through comprehensive analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-stimulated RAW264.7 macrophages. Curtachalasin Y1 (12), 5,6-dihydro-7-oxo-18-desoxy-19,20-epoxycytochalasin C (21), and 7-oxo-19,20-epoxycytochalasin C (22) exhibited potent inhibition, with IC₅₀ values of 55.4, 43.8, and 17.8 µM, respectively, compared to 14.9 μM for the positive control dexamethasone. Furthermore, these compounds suppressed lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines IL-6, MCP-1, and TNF-α, confirming their anti-inflammatory activity. Preliminary mechanistic investigation indicated that compound 22 exerts its anti-inflammatory effects in RAW264.7 cells by downregulating CXC motif chemokine ligand 10 (CXCL10) and upregulating suppressor of cytokine signaling 3 (SOCS3) expression. These results expand the structural diversity of cytochalasans from Xylaria species and provide a basis for further exploration of their anti-inflammatory potential.