Effects of Hispidulin on the Activity of Human Liver Cytochrome P450 Enzymes

Hispidulin is a flavonoid compound with a variety of pharmacological properties, and however, whether hispidulin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. In this study, the inhibitory effects of hispidulin on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs). The results showed that hispidulin inhibited the activity of CYP3A4 and 2E1, with IC50 values of 13.96 and 20.67 mu M, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that hispidulin was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1, with K-i values of 7.77 and 11.75 mu M, respectively. In addition, hispidulin is a time-dependent inhibitor for CYP2E1 with K-inact/KI value of 0.026/2.22 mu M(-1)min(-1). The in vitro studies of hispidulin with CYP isoforms indicate that hispidulin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4 and 2E1. Further clinical studies are also needed to evaluate the significance of this interaction.