1.Pristimerin (PTM) is a biological component isolated from Chinese herbal plant Celastrus and Maytenus spp. and it possesses numerous pharmacological activities. However, whether PTM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. 2.In this study, the inhibitory effects of PTM 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). 3.The results showed that PTM inhibited the activity of CYP1A2, 3A4 and 2C9, with IC 50 values of 21.74, 15.88 and 16.58 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that PTM was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60 and 8.09 μM, respectively. In addition, PTM is a time-dependent inhibitor for CYP3A4 with Kinact /KI value of 0.049/11.62 μM-1 min-1. 4.The in vitro studies of PTM with CYP isoforms indicate that PTM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, 3A4 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.
Keywords: CYP1A2; CYP2C9; CYP3A4; Herb–drug interaction; pristimerin.