Guxiaspergiltones A-J: Furanone-type polyketides with anti-inflammatory activities from the mangrove endophytic fungus Aspergillus sp. GXNUW29.

Eleven undescribed metabolites, including ten benzofuranone derivatives named guxiaspergiltones A-J (1-10) and one natural phenolic compound (11), were separated from the mangrove endophytic fungus Aspergillus sp. GXNUW29. The data of NMR, ECD, and HRESIMS analysis were used to determine these structures. Guxiaspergiltones A-D (1-4) are characterized by a unique structural feature: a distinctive benzofuranone scaffold embedded within the polyketide backbone. Bioactivity evaluation results demonstrated that compounds 1, 4, 5, and 10 significantly inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages, thereby exhibiting prominent anti-inflammatory activity. Specifically, compound 4 showed potent inhibitory effects on the expression of cyclooxygenase-2 (COX-2) at both the transcriptional and protein levels, the 50% maximum inhibitory value (IC50) is 10.1 ± 2.2 μM, whereas the IC50 value of the positive control was 24.6 ± 2.4 μM. Meanwhile, this compound also exerted a regulatory effect on the mitogen-activated protein kinase (MAPK) signaling pathway.