Effects of some commonly used Saudi folk herbal medications on the metabolic activity of CYP2C9 in human liver microsomes

Objective: To investigate the potential effects of eleven of the most commonly used Saudi folk herbal medications on the metabolic activity of CYP2C9 in human liver microsomes. Method: CYP2C9-mediated 40-hydroxylation of tolbutamide (TB) to 40-hydroxytolbutamide (4- OH-TB) was utilized to assess the metabolic activity of CYP2C9. In the present study, an initial screening of the eleven herbs was carried out by incubating TB with microsomes and NADPH in absence or presence of a fixed concentration (25 μg/ml) of alcoholic extracts of different herbs and the metabolite formed was measured by HPLC. Herbs that showed significant effects were further investigated at a lower range of concentration. Results: Among the investigated herbal extracts, only aniseed and curcuma showed statistically significant effects on the formation of 4-OH-TB in human liver microsomes. Curcuma produced a potent inhibition on the metabolite formation and its maximum (about 45% inhibition) was observed at the highest extract concentrations (10 and 25 μg/ml). On the other hand, aniseed signif- icantly activates the formation of 4-OH-TB and the maximum activation (about 55%) was observed at 2.5 μg/ml of aniseed extract. Conclusion: The results of this study have shown that alcoholic extracts of curcuma and aniseed were capable of inhibiting and activating; respectively, the CYP2C9-mediated 4-OH-TB formation in human liver microsomes, suggesting that these herbs have the potential to interact with CYP2C9 drug substrates. None of the other nine investigated herbs was able to produce any statistically significant effect.