CYP1A2 is the major isoform responsible for paeonol O-demethylation in human liver microsomes

Abstract

1. Paeonol, the primary active component of a traditional Chinese medicine Moutan Cortex, has a wide range of pharmacological activities. In the present study, the metabolism of paeonol by cytochrome P450s (CYPs) was investigated in human liver microsomes.

2. One O-demethylated metabolite was detected in reaction catalysed by human liver microsomes, and was identified as resacetophenone by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound.

3. The study with a chemical selective inhibitor, cDNA-expressed human CYPs, a correlation assay, and a kinetics study demonstrated that CYP1A2 was the major isoform responsible for the paeonol O-demethylation in human liver microsomes.

Keywords::

• Paeonol
• cytochrome P450
• O-demethylated metabolite.

Acknowledgements

This work was supported by the National Key Technology R&D Program in the 11th Five Year Plan of China (Grant Number 2008ZX10208), National Basic Research Program of China (Grant Number 2009CB522808), and the National Science & Technology Pillar Program in the 11th Five Year Plan of China (Grant Numbers 2006BAI11B08 and 2008BAI51B02).

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