Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp
Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp
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DOI：
10.1016/j.ijpharm.2009.05.022
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发表时间：
2009-08-13
影响因子：
5.8
通讯作者：
Zeng, Su
中科院分区：
文献类型：
--
作者：
Wang, Xiao-dan;Meng, Min-xin;Zeng, Su
本研究旨在了解落新妇苷和花旗松素在Caco-2细胞模型中的转运特性及其对P-糖蛋白功能和表达的影响。使用在Transwell插入物上培养的Caco-2细胞检查转运研究。用Western Blot和RT-PCR检测它们对P-糖蛋白功能和表达的影响。转运具有浓度和温度依赖性。在10-1000 μ M的浓度范围内，这两种化合物在分泌方向的表观渗透性（P-app）大于吸收方向。这些化合物对P-糖蛋白介导的罗丹明123转运没有影响。落新妇苷或紫杉叶素作用Caco-2细胞36 h，通过上调P-gp蛋白和mRNA表达，表现出较高的P-gp活性。这些结果表明，P-糖蛋白和多药耐药蛋白2可能在限制这些化合物的生物利用度方面起重要作用。作为P-糖蛋白或多药耐药蛋白2抑制剂的药物可能会增加落新妇苷或紫杉叶素的口服生物利用度，并可能产生不必要的药物-食物相互作用。Caco-2细胞中P-糖蛋白表达的增加可能是限制外源性物质进入体内的一种适应和防御机制。(C)2009爱思唯尔有限公司版权所有。
This study was designed to understand the transport profiles of astilbin and taxifolin in Caco-2 cell model and their effects on the function and expression of P-glycoprotein. The transport studies were examined using Caco-2 cells cultured on Transwell (R) inserts. Their effects on the function and expression of P-glycoprotein were detected using Western Blot and RT-PCR. The transport was concentration and temperature dependent. The apparent permeability (P-app) of these two compounds in the secretory direction was larger than that in the absorptive direction in the concentration range of 10-1000 mu M. Those compounds had no effects on the P-glycoprotein-mediated transport of Rhodamine 123. Caco-2 cells exposed to astilbin or taxifolin for 36 h exhibited higher P-glycoprotein activity through up-regulating P-glycoprotein expression at protein and mRNA levels. These results indicated that P-glycoprotein and Multidrug Resistance Protein 2 might play important roles in limiting the bioavailability of those compounds. Drugs which are the inhibitors of P-glycoprotein or Multidrug Resistance Protein 2 may increase the oral bioavailability of astilbin or taxifolin and the possibility of unwanted drug-food interactions. The increased expression of P-glycoprotein in Caco-2 cells may serve as an adaptation and defense mechanism in limiting the entry of xenobiotics into the body. (C) 2009 Elsevier B.V. All rights reserved.