In vitro inhibitory effects of dihydromyricetin on human liver cytochrome P450 enzymes.

Context:Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated fromAmpelopsis grossedentata(Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods:The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigatedin vitrousing human liver microsomes (HLMs). Results:The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC50values of 14.75, 25.74 and 22.69 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, withKivalues of 6.06, 9.24 and 10.52 μM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 withKI/Kinactvalue of 12.17/0.057 min−1 μM−1. Discussion and conclusion:Thein vitrostudies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction. [ABSTRACT FROM PUBLISHER]