辛芍提取物中5种成分在Caco-2细胞中的吸收特性  

Absorption characteristics of 5 components of Xinshao extract in Caco-2 cells

作　　者：侯佳[1] 胡建春[1] 李月婷[1,2] 刘亭[1,2] 黄勇[1,2] 王爱民[3,2] 

机构地区：[1]贵州医科大学贵州省药物制剂重点实验室,贵州贵阳550004 [2]贵州医科大学药学院,贵州贵阳550004 [3]贵州医科大学民族药与中药开发应用教育部工程研究中心,贵州贵阳550004

出　　处：《中国中药杂志》2016年第11期2137-2143,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81260636);贵州省科学技术基金项目(黔科合J字[2013]2035号);贵州省中药现代化专项(黔科合中药字[2013]5062号;黔科合重G字[2013]4001);贵州省中医药管理局项目(QZZY-2015-080);贵州省研究生卓越人才项目(黔教研合字[2014-1871]号);民族药与中药开发应用产学研基地建设项目(黔科合KY字[2013]122号)

摘　　要：研究辛芍提取物在Caco-2细胞中的吸收特性。该文建立人源结肠腺癌细胞系Caco-2细胞模型,采用UPLC-MS测定辛芍提取物中芍药内酯苷、没食子酸、咖啡酸、灯盏乙素、灯盏甲素5个活性成分在细胞裂解液中的含量。并用此模型分别研究p H,时间,温度以及药物浓度对辛芍提取物中芍药内酯苷等5种成分的吸收影响,并且考察在P-糖蛋白抑制剂存在与否时5种成分的转运情况,预测这5种成分在Caco-2细胞中的吸收机制。实验结果表明,在37℃下,辛芍组方提取物中5种成分的摄取具有一定的时间依赖性;在0.5~12.5 g·L^(-1),摄取呈浓度依赖性,符合被动扩散过程;在pH 4.0~7.4,咖啡酸、灯盏乙素、灯盏甲素3个成分的细胞吸收量随p H增加而显著降低(P<0.05);在4~37℃,咖啡酸的细胞吸收量随温度升高而降低,而其余4个成分随着温度升高而增加;加入P-糖蛋白抑制剂维拉帕米和环孢菌素A,咖啡酸与灯盏乙素的细胞摄取量显著增加(P<0.05)。说明辛芍提取物中芍药内酯苷等5种成分的吸收机制可能为被动扩散,且灯盏乙素和咖啡酸可能是P-糖蛋的底物。To study the absorption characteristics of Xinshao extracts in Caco-2 cells. In this paper, human colon adenocarcinoma cell line Caco-2 cell model was established, and UPLC-MS method was applied to determinate the contents of five components of Xinshao extracts（ albiflorin, gallic acid, caffeic acid, scutellarin and apigenin-7-O-glucronide） in cell lysates. This model was also used to study the effect of different drug concentrations, pH, time and temperature on the absorption of five components, investigate the transport of the five components of Xinshao extracts under the conditions with or without P-glycoprotein inhibitors, and predict the absorption mechanism of these five components in Caco-2 cells. The experimental results showed that the absorption of five components of Xinshao extracts in Caco-2 cells was time-dependent at 37 ℃, and concentration-dependent in the range of 0. 5-12. 5 g . L^-1 , with a passive diffusion mechanism. At the pH of 4-7.4, the absorption of caffeic acid, scutellarin and apigenin-7-O-glucronide was significantly declined with the increase of pH （P 〈 0. 05）. At the temperature of 4 to 37℃, the absorption of caffeic acid was declined with the increase of temperature, while the absorption of other four components was increased with the increase of temperature. Compared with the control group, caffeic acid and scutellarin cell absorption was significantly higher（P 〈 0. 05 ） after treatment with P-glycoprotein inhibi- tors（verapamil and cyclosporine A）. The results indicated that, the absorption mechanism of five components in Xinshao extracts may be of passive diffusion, and the caffeic acid and scutellarin may be the substrates of P-glycoprotein.

关 键 词：辛芍提取物 CACO-2细胞 吸收 UPLC-MS 被动扩散 

分 类 号：R285[医药卫生—中药学]