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In vitro Inhibition and Induction of Human Liver Cytochrome P450 Enzymes by Gentiopicroside: potent effect on CYP2A6.

Drug Metab Pharmacokinet. 2013 Feb 19;

Authors: Deng Y, Wang L, Yang Y, Sun W, Xie R, Liu X, Wang Q


Gentiopicroside (GE), a naturally occurring iridoid glycoside, has been developed into a Novel Traditional Chinese Drug named Gentiopicroside injection, and it was approved for the treatment of acute jaundice and chronic active hepatitis by SFDA. However, the inhibitory and inducible effects of GE on the activity of cytochrome P450 (CYP450) is unclear. The purpose of this study was to evaluate the ability of GE to inhibit and induce human cytochrome P450 enzymes in vitro. In human liver microsomes, GE inhibited CYP2A6 and CYP2E1 in a concentration-dependent manner, with IC(50) values of 21.8 µg/ml and 594 µg/ml, respectively, and the IC(50) of CYP2A6 was close to the C(max) value observed clinically. GE was a non-competitive inhibitor of CYP2A6 at lower concentration and a competitive inhibitor at higher concentration. GE did not produce inhibition of CYP2C9, CYP2D6, CYP1A2 and CYP3A4 activities. However, significant increase of CYP1A2 and CYP3A4 activity was observed at high concentrations. In cultured human hepatocytes no significant induction of CYP1A2, CYP3A4 and CYP2B6 was observed. Given these results, the in vivo potential inhibition of GE on CYP2A6 deserves further investigation, and it seems that the hepatoprotective effect of GE is irrelevant with its effect on P450s.

PMID: 23419353 [PubMed - as supplied by publisher]