葛根芩连汤有效成分对黄芩苷在Caco-2细胞模型中吸收转运的影响  

Influence of active ingredients in Gegen Qinlian Decoction on uptake and transport of baicalin in Caco-2 cell model

作　　者：顾青青[1] 邵以诺[1] 安叡[1] 王跃[1] 张艺竹[1] 王新宏[1] 

机构地区：[1]上海中医药大学,上海201203

出　　处：《中成药》2015年第4期694-699,共6页Chinese Traditional Patent Medicine

摘　　要：目的采用LC-MS/MS法研究葛根芩连汤(葛根、黄芩、黄连、甘草)有效成分对黄芩苷在Caco-2细胞模型中吸收转运的影响。方法建立Caco-2细胞模型,采用细胞摄取实验和细胞转运实验评价多药耐药相关蛋白(MRP2)的功能。结果摄取实验中,黄芩苷的摄取量在60 min基本达到饱和[(0.68±0.07)ng/μg],加入MRP2抑制剂MK-571之后,黄芩苷的摄取量显著升高[(1.10±0.02)ng/μg,P<0.01],而P-gp转运蛋白抑制剂维拉帕米无此效果。配伍葛根素能提高黄芩苷的摄取量(P<0.05),而小檗碱、甘草苷的作用有统计学意义。细胞转运实验的结果表明,加入MRP2转运蛋白抑制剂后能增加黄芩苷从肠腔侧(AP)到基底侧(BL)侧的转运。配伍葛根素、甘草苷后能促进黄芩苷从AP到BL侧的转运,小檗碱无明显影响。结论 MRP2转运蛋白调控Caco-2细胞摄取吸收黄芩苷,推测其可能为MRP2转运蛋白的底物。葛根素可使在Caco-2细胞中黄芩苷被外排的量减少,从而增加黄芩苷的吸收量。AIM To study the influence of the active ingredients in Gegen Qinlian Decoction（ Puerariae lobatae Radix,Scutellariae Radix,Coptidis Rhizoma,Glycyrrhizae Radix et Rhizoma） on the transporting properties of baicalin across Caco-2 cell model with LC-MS / MS. METHODS The established Caco-2 cell model was employed to evaluate the functions of multidrug resistance-associated protein 2（ MRP2） by cell uptake and cell transport experiments. RESULTS The results of cell uptake experiments showed that the saturated uptake of baicalin could reach（ 0. 68 ± 0. 07） ng / μg in 60 min. MRP2 inhibitor MK-571 could enhance the uptake of baicalin up to（ 1. 10 ± 0. 02） ng /μg（ P〈 0. 01）,while P-gp inhibitor Verapamil did not have similar effect. After the compatibility experiments,puerarin increased the uptake of baicalin（ P 〈0. 05）,whereas liquiritin was not of statistical significance. The cell transfer experiment indicated the addition of MRP2 inhibitor could increase the transport of baicalin from apical side to basolateral side. The combination of puerarin and liquiritin enhanced the transport of baicalin from apical side to basolateral side,but berberine presented no effect. CONCLUTION We could speculate that baicalin might be MRP2 transporter substrate in Caco-2 cell based on the experiment data and the fact that MRP2 transporter increases the absorption of baicalin. Puerarin can decrease the efflux of baicalin from the Caco-2cells,thus increasing its uptake.

关 键 词：葛根芩连汤 CACO-2 转运 多药耐药相关蛋白(MRP2) 黄芩苷 葛根素 甘草苷 小檗碱 

分 类 号：R965.2[医药卫生—药理学]