Inhibition of Cytochrome P450 Activities by Extract and Its Prenylated Flavonoids in Human Liver Microsomes.

possesses several pharmacological properties and has been widely used for the treatment of diarrhea, inflammation, abscess, dysentery, and fever in East Asian countries. is a major source of prenylated flavonoids, such as sophoraflavone and kushenol. In this study, we examined the effects of extract and its prenylated flavonoids on cytochrome P450 (CYP) isoform activity in human liver microsomes. The extract inhibited CYP2C8, CYP2C9, CYP2C19, and CYP3A activities, with IC values of 1.42, 13.6, 19.1, and 50 g/mL, respectively. CYP2B6 was only inhibited in human liver microsomes preincubated with the extract. CYP3A4 was more strongly inhibited by the extract in the presence of NADPH, suggesting that the extract may inhibit CYP2B6 and CYP3A4 via mechanism-based inactivation. Prenylated flavonoids also inhibited CYP isoforms with different selectivity and modes of action. Kushenol I, leachianone A, and sophoraflavone G inhibited CYP2B6, whereas kushenol C, kushenol I, kushenol M, leachianone A, and sophoraflavone G inhibited CYP3A4 via mechanism-based inhibition. Our results suggest that may contribute to herb-drug interactions when coadministered with drugs metabolized by CYP2B6, CYP2C8, CYP2C9, and CYP3A4.