Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Xin WangJohn H K Yeung

Abstract

This study investigated the effects of tanshinones on human CYP1A2 (phenacetin O-deethylase), CYP2C9 (tolbutamide 4-hydroxylase), CYP2E1 (chlorzoxazone 6-hydroxylase) and CYP3A4 (testosterone 6beta-hydroxylase) activities in vitro using pooled human liver microsomes and specific human CYP isoforms. Tanshinone I, tanshinone IIA, and cryptotanshinone were potent competitive CYP1A2 inhibitors (K(i)=1.5-2.5 microM); medium competitive inhibitors of CYP2C9 (K(i)=22-62 microM); medium competitive inhibitors of CYP2E1 (K(i)=3.67 microM) for tanshinone I and 10.8 microM for crytotanshinone; but weak competitive inhibitors of CYP3A4 (K(i)=86-220 microM). Dihydrotanshinone was a competitive inhibitor of human CYP1A2 (K(i)=0.53 microM) and CYP2C9 (K(i)=1.92 microM), a noncompetitive inhibitor of CYP3A4 (K(i)=2.11 microM) but an uncompetitive CYP2E1 inhibitor. In conclusion, these results showed that tanshinones inhibited the metabolism of various CYP probe substrates in human liver microsomes and specific human CYP isoforms in vitro. Given that CYP1A2, 2C9, 2E1 and 3A4 are responsible for the metabolism and disposition of a large number of drugs currently used, the potential herb-drug interactions of Danshen preparations containing the ma...Continue Reading

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Citations

Nov 14, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Furong QiuPing Miao
Dec 3, 2014·Chemico-biological Interactions·Ang ChenXin Wang
May 1, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xuelin ZhouJohn H K Yeung
Feb 7, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·John H K Yeung, Penelope M Y Or
Sep 9, 2011·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Wayne Y W LeeJohn H K Yeung
Jul 16, 2011·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·John H K Yeung, Penelope M Y Or
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Jul 22, 2011·Atherosclerosis·Si GaoSuowen Xu
Jul 18, 2014·Drug Metabolism and Pharmacokinetics·Shuoye YangXijing Chen
Nov 8, 2011·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xin Wang, John Hok-Keung Yeung
Feb 1, 2015·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Min SunXin Wang
Oct 30, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xuelin ZhouJohn H K Yeung
Oct 21, 2015·Chinese Journal of Natural Medicines·Shao-Jun Chen
Aug 10, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jin-Wen ZhaoXiao-Qi Ji
Mar 23, 2011·Phytotherapy Research : PTR·Xin Wang, John H K Yeung
May 6, 2017·BioMed Research International·Feng ChenDan-Dan Tian
Mar 27, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Zhaojian ZhangXiumei Gao
Sep 4, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jian LuXin Wang
Jun 3, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dongyi SunXin Wang

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