Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes

Abstract

Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.

Keywords::

• Triptolide
• cytochrome P450
• mono-hydroxylated metabolite

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 30772608 and 30630075), 973 Program (Grant Number 2009CB522808), National Science & Technology Pillar Program (Grant Number 2008BAI51BO2), and the Eleventh Five-Year Plan (Grant Number 2006BAI11B08).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.