Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract
Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract
复制标题
DOI：
10.1016/j.bbrc.2004.04.139
复制
发表时间：
2004-06-11
影响因子：
3.1
通讯作者：
Auclair, K
中科院分区：
文献类型：
--
作者：
Gaudineau, C;Beckerman, R;Auclair, K
测试了银杏叶提取物 EGb761 抑制主要人类细胞色素 P450 酶 (CYP) 的能力。完整提取物被发现强烈抑制 CYP2C9 (K-i = 14 +/- 4 mug/mL)，并在较小程度上抑制 CYP1A2 (K-i = 106 +/- 24 mug/mL)、CYP2E1 (K-i = 127 +/- 42 mug/mL) 和 CYP3A4 (K-i = 155 +/- 43)杯/毫升）。提取物的萜类和类黄酮部分分别针对相同的 P450 进行测试，以确定 EGb761 的抑制来源。萜类组分仅抑制 CYP2C9 (K-i = 15 +/- 6 mug/mL)，而 EGb761 的黄酮类组分对 CYP2C9、CYP1A2、CYP2E1 和 CYP3A4 表现出高度抑制作用（K-i 在 4.9 至 55 mug/mL 之间）。使用萃取和色谱法进一步对类黄酮级分进行分级。抑制研究表明，这些组分中的大多数以显着水平抑制 P450（IC50
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