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Xenobiotica
the fate of foreign compounds in biological systems
Volume 39, 2009 - Issue 5
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Research Article

Hydroxylation of tanshinone IIa in human liver microsomes is specifically catalysed by cytochrome P4502A6

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Pages 382-390 | Received 01 Jan 2009, Accepted 12 Feb 2009, Published online: 01 May 2009
 

Abstract

  1. Tanshinone IIa, the primary active component of a traditional Chinese medicine Salvia miltiorrhiza (Danshen), has a wide range of pharmacological activities. In the present study, the metabolism of tanshinone IIa (5 μM) by cytochrome P450s (CYPs) was investigated in human liver microsomes.

  2. One mono-hydroxylated metabolite was detected in a reaction catalysed by human liver microsomes, and was identified as tanshinone IIb 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 cytochrome P450s, correlation assay, and kinetics study demonstrated that CYP2A6 was the specific isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 μM) in human liver microsomes.

Acknowledgements

This work was supported by the National Key Technology R&D Program in the 11th Five Year Plan of China (Grant Number 2008ZX10208), 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.

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