摘要
目的 研究蒙药塔布森-2(Tabson-2 decoction,TBD)中苯丙素类成分在Caco-2细胞中的吸收特性,初步阐明TBD的口服吸收机制。方法 采用Caco-2细胞单层细胞模型,通过UPLC-MS/MS分析TBD在Caco-2细胞中的摄取成分,并建立UPLC-MS/MS分析方法测定TBD中吸收最好的9种苯丙素类成分原儿茶酸、新绿原酸、绿原酸、隐绿原酸、1,5-二咖啡酰奎宁酸、异绿原酸C、咖啡酸、二氢咖啡酸、3-羟基肉桂酸在Caco-2细胞中的含量,分别考察时间、浓度和P糖蛋白抑制剂对各成分的吸收影响。结果 研究发现咖啡酸、二氢咖啡酸的总摄取量在0~180 min为上升趋势,未呈现饱和;3-羟基肉桂酸在90 min左右吸收恒定趋于饱和;隐绿原酸、1,5-二咖啡酰奎宁酸、异绿原酸C、新绿原酸、绿原酸、原儿茶酸的摄取量约从90 min开始,随时间的增加先下降后上升。与苯丙素类成分相比,加入P-糖蛋白抑制剂维拉帕米及环孢菌素A后对二氢咖啡酸的吸收产生了影响,说明二氢咖啡酸是P-糖蛋白底物。结论 TBD主要苯丙素类成分进入Caco-2细胞以被动扩散为主,主动转运为辅,且除二氢咖啡酸外其他8个成分的吸收过程不受P-糖蛋白的外排作用影响。
OBJECTIVE To study the absorption characteristics of phenylpropanoids of Mongolian medicine Tabson-2decoction(TBD) in Caco-2 cells and to preliminarily clarify the oral absorption mechanism of TBD.METHODS Caco-2 cell monolayer model was used to analyze the uptake components of TBD in Caco-2 cells by UPLC-MS/MS,and UPLC-MS/MS analysis method was established to determine the nine best absorbed components of TBD,protocatechuic acid,neochlorogenic acid,chlorogenic acid,cryptogenic acid,1,5-dicaffeinate quinic acid,isochlorogenic acid C,caffeic acid,dihydrocaffeic acid,chlorogenic acid.The effects of time,concentration and P-glycoprotein inhibitor on the absorption of each component were investigated.RESULTS The overall intake of caffeic acid and dihydrocaffeic acid showed an upward trend in 0-180 min,and did not show saturation.The absorption of 3-hydroxycinnamic acid was constant at about 90 min and tended to saturation.The intakes of cryptochlorogenic acid,1,5-dicaffeinate,quinic acid,isochlorogenic acid C,neochlorogenic acid,chlorogenic acid and protocatechuic acid first decreased and then increased with time from about 90 min.The addition of P-glycoprotein inhibitor verapamil and cyclosporin A had an effect on the absorption of dihydrocaffeic acid compared with the phenylpropanoid components,indicated that dihydrocaffeic acid was the substrate of P-glycoprotein.CONCLUSION The main phenylpropanoids of TBD enter Caco-2 mainly by passive diffusion,supplemented by active transport,and the absorption process of the other eight components is not affected by the efflux of P-glycoprotein except dihydrocaffeic acid.
作者
李春燕
王曦悦
陆景坤
董馨
赵鹏伟
马飞祥
薛培凤
LI Chunyan;WANG Xiyue;LU Jingkun;DONG Xin;ZHAO Pengwei;MA Feixiang;XUE Peifeng(Inner Mongolia Medical University,Hohhot 010110,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2023年第15期2048-2055,共8页
Chinese Journal of Modern Applied Pharmacy
基金
国家自然科学基金项目(81860756,81960758)
内蒙古自治区科技创新引导项目(02039001)
内蒙古自治区自然科学基金项目(2019MS08111)。
