银杏叶提取物及其萜类单体对人孕烷X受体介导CYP3A4转录的调节作用  

Regulative Effects of Ginkgo Biloba Extract and Its Terpenoids on the Orphan Human Pregnane X Receptor Mediated Transcriptional Activation of CYP3A4

作　　者：邓颖[1,2] 赵立子[1] 毕惠嫦[1] 潘莹[1,3] 潘道苇[1] 欧志敏[1] 黄民[1] 

机构地区：[1]中山大学临床药理研究所,广州510080 [2]深圳市宝安人民医院药剂科,广东深圳518101 [3]中山大学肿瘤防治中心药剂科,广州510060

出　　处：《中药新药与临床药理》2009年第3期234-237,共4页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广州市重大项目(2004Z1-E4051)

摘　　要：目的研究银杏叶提取物(GBE)及其萜类单体白果内酯(BB)、银杏内酯A(GA)和银杏内酯B(GB)是否能通过孕烷X受体(PXR)的活化而诱导CYP3A4转录。方法采用脂质体瞬时转染的方法,在人肝肿瘤细胞株HepG2细胞中转入PXR表达质粒、CYP3A4报告基因质粒和内参质粒,与不同浓度的银杏叶提取物及其萜类单体(BB、GA和GB)共同孵育24h后,检测细胞中荧光素酶。结果GBE(100ng/mL、500ng/mL、5μg/mL和25μg/mL)分别通过活化PXR诱导CYP3A41.32、1.57、1.71和1.92倍,BB(10ng/mL、100ng/mL和1μg/mL)分别通过活化PXR诱导CYP3A41.52、1.79和1.89倍,GA和GB则不能通过活化PXR诱导CYP3A4。结论GBE和BB能通过PXR的活化而诱导CYP3A4转录,GA和GB不能活化PXR,对CYP3A4转录无诱导作用,提示在GBE或BB与CYP3A底物合用时要注意药物之间的相互作用。Objective To examine the effects of Ginkgo biloba extract （GBE） and its terpenoids of bilobalide （BB）, ginkgolide A （GA） and ginkgolide B （GB） on the orphan human pregnane X receptor （PXR） mediated transcriptional activation of CYP3A4. Methods Transient cotransfection reporter gene assays were performed on HepGz cells with the PXR expression plasmid and the reporter plasmid of CYP3A4 linked to luciferase. The CYP3A4 activation was confirmed by measuring the activity of luciferase. Results GBE in the concentration range of 100 ng/mL - 25 μg/mL and BB in the concentration range of 10 ng/mL- 1 μg/mL significantly increased CYP3A4 transcription in HepG2 cells. GA and GB cannot induce CYP3A4 transcription in HepG2 cells. Conclusion GBE and BB can induce the CYP3A4 transcription through PXR pathway, but GA and GB have no effect on PXR - mediated transcription of CYP3A4. Therefore, the interaction of GBE or BB with CYP3A4 should be taken into account when they are used together.

关 键 词：银杏叶提取物 白果内酯 银杏内酯A 银杏内酯B 孕烷X受体 CYP3A4 

分 类 号：R285.5[医药卫生—中药学]