A bile acid derivative with PPARγ-mediated anti-inflammatory activity.

Area of Science:

• Natural Product Chemistry
• Pharmacology
• Immunology

Background:

• Jellyfish-derived fungi are a source of novel bioactive compounds.
• Inflammation is implicated in numerous diseases and targeted by various therapies.
• Peroxisome proliferator-activated receptor gamma (PPARγ) is a therapeutic target for inflammatory conditions.

Purpose of the Study:

• To isolate and characterize bioactive secondary metabolites from Penicillium chrysogenum.
• To investigate the anti-inflammatory potential of isolated compounds.
• To elucidate the molecular mechanism of action of the novel steroidal artifact.

Main Methods:

• Isolation and structure elucidation of secondary metabolites using chromatographic and spectroscopic techniques.
• In vitro anti-inflammatory assays using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.
• Molecular docking analysis to predict ligand-receptor interactions.
• Cell-based assays to assess PPARγ activation and NF-κB signaling pathway modulation.

Main Results:

• A new steroidal artifact (1) and several bile acid derivatives were isolated from Penicillium chrysogenum.
• Compound 1 demonstrated significant anti-inflammatory effects by suppressing nitric oxide (NO) production and pro-inflammatory gene expression (iNOS, TNF-α).
• Docking analysis and cell-based assays revealed that compound 1 acts as a steroidal PPARγ activator, inhibiting the NF-κB signaling pathway.

Conclusions:

• Compound 1, a novel steroidal artifact from jellyfish-derived fungus, possesses potent anti-inflammatory properties.
• The anti-inflammatory mechanism involves the activation of PPARγ and subsequent suppression of the NF-κB signaling pathway.
• This study highlights the potential of marine-derived fungi as a source of novel anti-inflammatory agents.