In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melengueta and Dennettia tripetala extracts

Objective: To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs. Aframomum melengueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes. Methods: In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in viva effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non -compartmental anaysis as implemented in WinNonlin pharmacokinetic program. Results: EMND assay with intestinal microsomes indicated that aqueous extracts of D. trim:tutu and A. meleugueut significantly (P < 0.05) inhibited intestinal CYP 3A activity at both 50 mu g and 100 mu g concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3A activity at 100 mu g but not at 50 mu g concentrations. All the extracts showed an in vitro, dose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pretreatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin (P < 0.05). Conclusions: Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.