Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract

被引：111

作者：

Gaudineau, C ^{[1
]}

Beckerman, R ^{[1
]}

Welbourn, S ^{[1
]}

Auclair, K ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 318卷 / 04期

关键词：

Ginkgo biloba; CYP; P450; inhibition; flavonoids; terpenoids; ginkgolides; bilobalide;

D O I：

10.1016/j.bbrc.2004.04.139

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Ginkgo biloba extract EGb761 was tested for its ability to inhibit the major human cytochrome P450 enzymes (CYPs). The full extract was found to strongly inhibit CYP2C9 (K-i = 14 +/- 4 mug/mL), and to a lesser extent, CYP1A2 (K-i = 106 +/- 24 mug/mL), CYP2E1 (K-i = 127 +/- 42 mug/mL), and CYP3A4 (K-i = 155 +/- 43 mug/mL). The terpenoidic and flavonoidic fractions of the extract were tested separately against the same P450s to identify the source of inhibition by EGb761. The terpenoidic fraction inhibited only CYP2C9 (K-i = 15 +/- 6 mug/mL) whereas the flavonoidic fraction of EGb761 showed high inhibition of CYP2C9, CYP1A2, CYP2E1, and CYP3A4 (K-i's between 4.9 and 55 mug/mL). The flavonoidic fraction was further fractionated using extraction and chromatography. Inhibition studies indicated that the majority of these fractions inhibited P450s at a significant level (IC50<40 mug/mL). (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：1072 / 1078

页数：7

共 47 条

[1] In vivo regulation of peripheral-type benzodiazepine receptor and glucocorticoid synthesis by Ginkgo biloba extract EGb 761 and isolated ginkgolides [J].