摘要
目的:研究银杏叶提取物及其中2种主要活性物质黄酮和内酯对人体内CYP3A4酶活性的影响。方法:构建了可用于体外高通量检测基于PXR诱导的CYP3A4系统,通过细胞培养实验,化学发光检测仪检测银杏叶不同组分对CYP3A4的激活水平。采用反相高效液相色谱法测定银杏叶不同组分对细胞内尼卡地平代谢的影响。结果:高通量检测系统检测表明,银杏叶提取物对体内的CYP3A4酶表达具有显著的激活作用。进一步研究证实银杏叶提取物的两类主要活性物质黄酮和内酯呈剂量的方式激活CYP3A4的表达。银杏叶内酯明显加速尼卡地平的代谢速率,而银杏叶黄酮则降低细胞内尼卡地平的降解速率。结论:银杏叶提取物及其主要活性成分黄酮和内酯能显著提高CYP3A4的活性,内酯能提高CYP3A4代谢尼卡地平的能力,而黄酮则可能由于药物相互作用的原因,抑制了CYP3A4酶活性,降低其代谢尼卡地平的能力。
Objective：To determine effects of Ginkgo biloba extracts,ginkgolides and flavonoid fractions from the extracts on the activity of CYP3A4.Methods：Constructed a high throughput screening system for detecting induction of CYP3A4 mediated by PXR.In cell culture,chemiluminescence detector was used to detect the activation levels of CYP3A4 by different extracts from Ginkgo biloba,and reversed phase high performance liquid chromatographic method was used to monitor the degradation levels of nicardipine in the cells by different extracts from Ginkgo biloba.Results：Ginkgo biloba extracts activated PXR-mediated transcription of CYP3A4.Ginkgolides and flavonoid fractions from the extracts enhanced PXR-mediated transcription of CYP3A4 in a concentration-dependent manner.Ginkgolides enhanced the metabolic rate of nicardipine;while flavonoid fractions inhibited the metabolism of nicardipine in the cells.Conclusion：Ginkgo biloba extracts,ginkgolides and flavonoid fractions from the extracts can highly enhance the activity of CYP3A4.Ginkgolides enhanced the ability of CYP3A4 to degrade nicardipine in the cells,while flavonoid fractions inhibited it possibly by the drug interaction.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2011年第9期809-812,共4页
Chinese Journal of New Drugs
基金
福建省卫生厅青年基金(2010-01-30)
