Caco-2细胞单层模型研究黄芩提取物中黄芩苷转运机制及白芷提取物对其转运的影响  

Study on transport mechanism of baicalin in Scutellariae Radix extracts and effect of Angelica Dahurica extracts on transport of baicalin by Caco-2 cell monolayer model

作　　者：梁新丽[1,2] 朱梦良[1] 招丽君[1] 赵国巍[1] 廖正根[1] 曹运朝[1] 杨明[1] 

机构地区：[1]江西中医学院现代中药制剂教育部重点实验室,江西南昌330004 [2]成都中医药大学,四川成都610075

出　　处：《中国中药杂志》2013年第14期2389-2393,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30960516);国家"重大新药创制"科技重大专项(2009ZX09310-005);江西省自然科学基金项目(20114BAB215040)

摘　　要：目的:研究黄芩提取物中黄芩苷的吸收转运机制以及白芷提取物对其吸收影响,分析探讨白芷提取物对黄芩苷转运的影响机制。方法:建立人源结肠腺癌细胞系Caco-2细胞模型,利用此模型研究pH、时间、药物浓度、温度对黄芩提取物中黄芩苷的转运影响;研究黄芩苷在P-gp,MRP蛋白专属抑制剂存在与否时黄芩苷在Caco-2细胞模型的双向转运情况;并考察白芷提取物对黄芩苷吸收转运的影响。结果:37℃环境下黄芩苷转运在pH 7.4条件下吸收较好,且存在浓度依赖性;4℃环境下蛋白失活,转运量降低;黄芩苷双向转运PDR为0.54,P-gp抑制剂维拉帕米、MRP抑制剂丙磺舒加入后,黄芩苷BL→AP转运减少,而PDR无差异。加入白芷活性成分香豆素、挥发油、香豆素与挥发油混合物后黄芩苷转运分别提高了2.34,3.31,3.13倍。结论:黄芩苷主要转运机制为被动转运,兼有外排蛋白参与。白芷活性成分对黄芩苷有促吸收作用,此作用可能与黄芩苷的被动转运机制有关,白芷提取物打开了细胞间的紧密连接,也可能与白芷抑制外排蛋白的表达或功能有关。Objective： To study the transport mechanism of baicalin of Scutellariae Radix extracts and the effect of Angelica dahurica extracts on the intestinal absorption of baicalin by using Caco-2 cell monolayer model,in order to analyze the effect mechanism of Angelica dahurica extracts on the intestinal absorption of baicalin.Method： The Caco-2 cell monolayer model was established with human colonic adenocarcinoma cells,and used to study the effect of pH,time,drug concentration and temperature on the transport of baicalin in Scutellariae Radix extracts,the effect of P-gp and MRP protein-dedicated inhibitors on the bidirectional transport of baicalin in Caco-2 cell model,and the effect of angelica root extracts on baicalin absorption and transport.Result： Baicalin was absorbed well at 37 ℃ and under pH 7.4 condition and concentration dependent.Its proteins became inactive at 4 ℃,with a low transport.The bi-drectional transfer PDR was 0.54.After P-gp inhibitor verapamil and MRP inhibitor probenecid were added,the value of PappBL-AP of baicalin decreased,but without any difference in PDR.The transport of baicalin was improved by 2.34,3.31 and 3.13 times,after A.dahurica extract coumarin,volatile oil,and mixture of coumarin and volatile oil.Conclusion： The transport mechanism of baicalin is mainly passive transfer and supplemented with efflux proteins involved.A.dahurica extracts can enhance the absorption of baicalin,which may be related to the passive transfer merchanism of baicalin.A.dahurica extracts′ effect in opening the close junction among cells may be related to its expression or function in inhibiting efflux proteins.

关 键 词：CACO-2细胞模型 白芷提取物 黄芩苷 转运机制 P-gp MRP 

分 类 号：R285.5[医药卫生—中药学]