白芷香豆素类化合物与P-糖蛋白体外亲和作用研究  

In vitro study on affinity of coumarins in Angelicae Dahuricae Radix and P-gp

作　　者：董伟[1] 管雪静 廖正根[1] 卢雪萍[1] 梁新丽[1] 朱卫丰[1] 

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中草药》2016年第16期2893-2896,共4页Chinese Traditional and Herbal Drugs

基　　金：江西省青年科学基金资助项目(20161ACB21020);江西省青年科学家培养对象资助项目(20153BCB23019);国家青年自然科学基金资助项目(81303237);中国博士后基金(2016M590606)

摘　　要：目的研究白芷香豆素类化合物(欧前胡素、异欧前胡素、佛手柑内酯、氧化前胡素)在体外对P-糖蛋白(P-gp)三磷酸腺苷(ATP)酶活性的影响,进而探讨白芷香豆素类成分影响P-gp介导药物转运的机制。方法采用ATP酶活性测试法判断白芷香豆素类化合物是否为P-gp的底物。结果欧前胡素和氧化前胡素各质量浓度组平均荧光强度值(ΔRLUTC)均大于基础平均荧光强度值(ΔRLUbasal);异欧前胡素中、低质量浓度组及佛手柑内酯高、低质量浓度组ΔRLUTC小于ΔRLUbasal。结论欧前胡素和氧化前胡素为非浓度依赖的P-gp ATP酶抑制剂,异欧前胡素、佛手柑内酯在低质量浓度时可抑制ATP酶活性,对P-gp具有抑制作用;在高质量浓度时可诱导ATP酶活性,对P-gp具有诱导作用。Objective To study the effects of coumarins in Angelicae Dahuricae Radix （imperatorin, isoimperatorin, bergapten, and oxypeucedanin） on the activities of adenosine triphosphate （ATPase） in P-glycoprotein （P-gp） in vitro and to investigate the P-gp mediated meschanism in transport of drug. Methods The ATPase activity assay was used to identify whether the coumarins in Angelicae Dahuricae Radix were P-gp substrates or not. Results The average fluorescent values （ARLUTc） of imperation and oxypeucedanin at each concentration were greater than average basic fluorescence value （ARLUbasal）. The average fluorescent values （ARLUTc） in medium and low concentration of isoimperatorin and bergapten groups were lower than average basic fluorescence value （ARLUbasal）. Conclusion Imperation and oxypeucedanun are non-concentration dependent P-gp ATP inhibitors. Isoimperatorin and bergamot lactones could inhibit the ATPase activity at low concentration and have the inhibitory effect on P-gp. At high concentration, the activity of ATPase can be induced so as to induce P-gp.

关 键 词：白芷 香豆素类 P-糖蛋白 亲和力 欧前胡素 异欧前胡素 佛手柑内酯 氧化前胡素 

分 类 号：R285.5[医药卫生—中药学]