title: In vitro inhibitory effects of pristimerin on human liver cytochrome P450 enzymes.
abstract: 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 IC50values 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 Kivalues of 7.33, 11.60 and 8.09 μM, respectively. In addition, PTM is a time-dependent inhibitor for CYP3A4 with Kinact/KIvalue of 0.049/11.62 μM-1min-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.
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Hao
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Jianlei
authors.initials: J
authors.lastname: Yuan
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Yansen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Hou
authors.affiliation: a Cangzhou People's Hospital , Cangzhou , China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
mesh_terms: D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology*; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C050414:celastrol
keywords: CYP1A2; CYP2C9; CYP3A4; Herb–drug interaction; pristimerin