Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro
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摘要This study investigated the effects of tanshinones on human CYP1A2 (phenacetin O-deethylase), CYP2C9 (tolbutamide 4-hydroxylase), CYP2E1 (chlorzoxazone 6-hydroxylase) and CYP3A4 (testosterone 6 beta-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 mu M); medium competitive inhibitors of CYP2C9 (K(i) = 22-62 mu M); medium competitive inhibitors of CYP2E1 (K(i) = 3.67 mu M) for tanshinone land 10.8 mu M for crytotanshinone; but weak competitive inhibitors of CYP3A4 (K(i) = 86-220 mu M) Dihydrotanshinone was a competitive inhibitor of human CYP1A2 (K(i) = 0.53 mu M) and CYP2C9 (K(i) = 1.92 mu M), a noncompetitive inhibitor of CYP3A4 (K(i) = 2.11 mu M) 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 major tanshinones with drugs which are substrates of these CYPs may be important. (C) 2010 Elsevier GmbH. All rights reserved.
著者Wang X, Cheung CM, Lee WYW, Or PMY, Yeung JHK
期刊名稱Phytomedicine
出版年份2010
月份9
日期1
卷號17
期次11
出版社ELSEVIER GMBH, URBAN & FISCHER VERLAG
頁次868 - 875
國際標準期刊號0944-7113
電子國際標準期刊號1618-095X
語言英式英語
關鍵詞CYP1A2; CYP2C9; CYP2E1; CYP3A4; Danshen (Salvia miltiorrhiza); Human liver microsomes; In vitro; Tanshinones
Web of Science 學科類別Chemistry, Medicinal; CHEMISTRY, MEDICINAL; Integrative & Complementary Medicine; INTEGRATIVE & COMPLEMENTARY MEDICINE; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Plant Sciences; PLANT SCIENCES

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