Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba

Objective: We evaluated the potential of 15 herbal medicines (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms and microsomal NADPH-CYP reductase. Methods: The abilities of 1-1000 μg/mL of freeze-dried aqueous extracts of 15 HMs to inhibit phenacetin O-deethylation (CYP1A2), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4′-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), midazolam 1-hydroxylation (CYP3A4) and NADPH-CYP reductase were tested using human liver microsomes. Results: The HMs Epimedii herba, Glycyrrhizae radix and Leonuri herba inhibited one or more of the CYP isoforms or NADPH-CYP reductase. Of the three HMs, Epimedii herba extracts were the most potent inhibitors of several CYP isoforms (IC₅₀ 67·5 μg/mL for CYP2C19, 104·8 μg/mL for CYP2E1, 110·9 μg/mL for CYP2C9, 121·9 μg/mL for CYP3A4, 157·8 μg/mL for CYP2D6 and 168·7 μg/mL for CYP1A2) and NADPH-CYP reductase (IC₅₀ 185·9 μg/mL). Conclusion: These results suggest that some of the HMs used in Korea have the potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts. Controlled trials to test the significance of these results are necessary.