Selective Inhibition of Bakuchicin Isolated fromPsoralea corylifoliaon CYP1A in Human Liver Microsomes

Abstract

Bakuchicin is a furanocoumarin isolated fromPsoralea corylifoliaand shows several biological activities. Although there have been studies on the biological effects of bakuchicin, its modulation potency of CYP activities has not been previously investigated. Here, we investigated the inhibitory effects of bakuchicin on the activities of CYP isoforms by using a cocktail of probe substrates in pooled human liver microsomes (HLMs) and human recombinantcDNA-expressedCYP. Bakuchicin strongly inhibited CYP1A-mediated phenacetinO-deethylation with an IC50value of 0.43 μM in HLMs. It was confirmed by human recombinantcDNA-expressedCYP1A1 and CYP1A2 with aKivalue of 0.11 μM and 0.32 μM, respectively. A Lineweaver-Burk plot indicated that the inhibition mechanism of bakuchicin was competitive inhibition. Overall, this is the first study to investigate the potential CYP1A1 and CYP1A2 inhibition associated with bakuchicin and to report its competitive inhibitory effects on HLMs.