Aim To assess the potential effect of quercetin （QU）, an natural plant estrogen, on CYP1A2, CYP2E1, and CYP3A2 activities in rat liver microsomes; and to identify the magnitude of inhibitory effect and the probable inhibitory mechanism of QU. Methods QU and specific substrate were concurrently incubated, with HPLC detection of the substrate metabolites for data analysis. The magnitude of inhibitory effect of QU on CYP3A2 was compared with those of ketoconazole （Ket） and erythromycin （Ery）. The mechanism of its inhibitory effect on CYP3A2 and CYP2E1 was derived from Lineweaver-Burk plots. Results HPLC methods were in good linear relationship with r〉0.999 1. Relative standard deviations for intra-day and inter-day were〈8.4%. Recovery of each analyte in the concentrations studied was between 91.1% and 107.6 %. QU （up to 8 μmol·L^-1） showed potent induction to CYP1A2 （338.1% of the negative control）while inhibited CYP2E1 （49.2% of the negative control） and CYP3A2 （60.3% of the negative control） activity. The magnitude of inhibitory effect for QU on CYP3A2 was between those for Ket and Ery （Ket〉QU〉Ery）. QU exhibited competitive inhibition of CYP3A2 dextromethorphan N-demethylation reaction and expressed noncompetitive inhibition of CYP2E1 chlorzoxazone-6-hydroxylation reaction. Conclusion HPLC assay has been validated with precision and accuracy. QU is an effective inhibitor of several CYP isoforms. It may cause relevant drug-drug interactions with CYP3A substrates. As a plant flavonoid, QU has potential not only in molecular advantage but also in CYP450 module capability for further application in cancer chemotherapy.
