National Institute of Health and Nutrition, Tokyo, Japan.
Phytomedicine. 2012 Jan 15;19(2):177-82. doi: 10.1016/j.phymed.2011.06.020. Epub 2011 Jul 30.
Ginkgo biloba extract (GBE) is a popular herbal ingredient used worldwide, but it is reported to induce bleeding as a serious adverse event. In this study we examined whether GBE induced spontaneous bleeding or accelerated warfarin anticoagulation via herb-drug interaction. Mice were given GBE or various active components of GBE orally for 5 days and blood coagulation parameters and hepatic cytochrome P450 enzymes (CYPs) were measured. Mice also received warfarin (racemate, (S)- or (R)-enantiomer) for the last 3 days of the 5-day regimen to examine GBE-warfarin interactions. Neither GBE (up to 1000 mg/kg) nor ginkgolide B (up to 140 mg/kg), a platelet-activating factor antagonist, influenced blood coagulation parameters. In contrast, GBE attenuated the anticoagulant action of warfarin. Bilobalide, a component of GBE that markedly induced hepatic CYPs including (S)-warfarin hydroxylase, showed similar effects. For (S)-warfarin, the anticoagulation action and the interaction with GBE was clear, while the influence on metabolism was greater for (R)-warfarin than for (S)-warfarin, which corresponded to the CYP types induced by GBE. These results suggest that GBE and ginkgolide B have no influence on blood coagulation in vivo, and that GBE attenuates the anticoagulation action of warfarin via induction of hepatic CYPs by bilobalide.
银杏叶提取物（GBE）是一种在全球范围内广泛使用的流行草药成分，但据报道它会引起出血等严重的不良反应。在这项研究中，我们研究了银杏叶提取物是否通过草药-药物相互作用引起自发性出血或加速华法林抗凝作用。小鼠口服给予银杏叶提取物或其各种活性成分 5 天，测量血液凝血参数和肝细胞色素 P450 酶（CYPs）。小鼠还在 5 天疗程的最后 3 天接受华法林（消旋体、（S）-或（R）-对映体）治疗，以研究银杏叶提取物-华法林相互作用。银杏叶提取物（高达 1000mg/kg）或银杏内酯 B（高达 140mg/kg），一种血小板激活因子拮抗剂，均不影响血液凝血参数。相比之下，银杏叶提取物减弱了华法林的抗凝作用。银杏叶提取物的一种成分，白果内酯，显著诱导包括（S）-华法林羟化酶在内的肝细胞 CYP，表现出类似的作用。对于（S）-华法林，抗凝作用和与银杏叶提取物的相互作用很明显，而对于（R）-华法林，其代谢影响大于（S）-华法林，这与银杏叶提取物诱导的 CYP 类型相对应。这些结果表明，银杏叶提取物和银杏内酯 B 对体内血液凝血没有影响，而白果内酯通过诱导肝细胞 CYP 减弱了华法林的抗凝作用。
