Talarosterols A-C: Steroid-Xanthone Conjugates Featuring Octacyclic and Decacyclic Frameworks with Anti-Inflammatory Activity from Mangrove Endophytic Fungus Talaromyces sp.

Three novel steroid-xanthone conjugates, talarosterols A-C (1-3, respectively), were isolated from mangrove endophytic fungus Talaromyces sp. JNQQJ-4 using a molecular networking strategy. Their structures were determined by spectroscopic analyses, X-ray diffraction, DP4+ analysis, and ECD calculations. Compounds 1 and 2 possess unprecedented 6/6/6/5/6/6/6/6 octacyclic ring systems, whereas 3 features a unique 6/6/6/3/5/6/6/6/6/5 decacyclic ring system. Compounds 1 and 3 showed potent anti-inflammatory activity in RAW264.7 cells. Mechanistic studies showed that compound 1 suppressed pro-inflammatory cytokine expression via the UPP1/MAPK signaling pathway.