Abstract
During our search for bioactive secondary metabolites in the jellyfish-derived fungus Penicillium chrysogenum J08NF-4, several bile acid derivatives (2–6) were isolated along with a new steroidal artifact (1). An in vitro anti-inflammatory assay showed that pretreatment with 1 suppressed NO production and the gene expressions of the pro-inflammatory mediators iNOS and TNF-α in LPS-induced RAW 264.7 macrophages. Docking analysis of 1 revealed that it might bind to the ligand binding domain (LBD) of PPARγ in a manner similar to that of the synthetic steroid mifepristone (7), which is used clinically to treat hypercortisolism and was recently reported to be a PPARγ agonist. Compound 1 activated PPARγ in murine Ac2F liver cells and suppressed the LPS-induced phosphorylation of the NF-κB p65 subunit leading to downregulation of pro-inflammatory mediators.Our findings suggest that 1 acts as a steroidal PPARγ activator that downregulates the expressions of pro-inflammatory mediators by suppressing the NF-κB signaling pathway.
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