Furocoumarins from Cnidium monnieri Act as Peroxisome Proliferatoractivated Receptor γ and Farnesoid X Receptor Agonists

The fruit of Cnidium monnieri (L) Cusson is an important traditional medicine employed in Taiwan and China as the treatments of impotence, sterilization, renal disease, dermatosis, colpitis, inflammation and gynecological disease. Peroxisome Proliferator-activated Receptor γ (PPARγ) and Farnesoid X receptor (FXR) are the members of nuclear receptor superfamily that have been targeted for developing treatments for chronic liver diseases. In this study, the furocoumarins isolated from the fruit of Cnidium monnieri (L) Cusson were evaluated for their PPARγ and FXR agonism. Indeed, in transient transfection reporter assays, these furocoumarins transactivated PPARγ and FXR to respectively modulate promoter action including ABCA1 and SHP promoters in dose-dependent manner. Through the molecular modeling docking studies these furocoumarins were shown to bind to PPARγ or FXR ligand binding pocket fairly well. All these results indicate that Cnidium monnieri (L) Cusson might possess therapeutic effects through the activation of PPARγ and FXR pathways.