2004 Volume 21 Issue 6 Pages 281-286
A total of 26 herbal medicines were examined for their inhibitory effects on cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6). A methanol extract of each herbal medicine was prepared and then preincubated with human liver microsomes in the presence of an NADPH-generating system. Residual microsomal CYP3A4 and CYP2D6 activity was then determined by measuring the N-demethylation of erythromycin and the O-demethylation of dextromethorphan, respectively. Of the 26 herbal medicines tested, 16 were found to decrease the residual CYP3A4 activity in a preincubation time-dependent manner. The extract of Evodia Fruit caused the most dramatic decrease in residual CYP3A4 activity (i.e. 22.3% residual activity after 30 min preincubation). A substantial decrease in residual CYP3A4 activity was also observed from extracts of Sappan Wood, Incised Notopterygium Rhizome, Schisandra Fruit, Great Burdock Achene, Angelica Dahurica Root and Rhubarb (residual activity of 40.6, 41.2, 53.4, 47.1, 53.4 and 59.2% after 30 min preincubation, respectively). These results are comparable to those using troleandomycin, a known irreversible inhibitor of CYP3A4, which gave a residual activity of 49.4% under identical conditions. We found 5 herbal medicines that showed a preincubation time-dependent inhibition of CYP2D6. The extract of Incised Notopterygium Rhizome caused the most dramatic decrease in residual CYP2D6 activity (i.e. 61.9% residual activity after 30 min preincubation). These results suggest that extracts of herbal medicines contain metabolism-dependent inhibitors of CYP, especially CYP3A4.
