The effect of phytic acid on tight junctions in the human intestinal Caco-2 cell line and its mechanism

被引：41
|
作者：
Fu, Qingxue [1 ,2 ]
Wang, Huizhen [2 ]
Xia, Mengxin [2 ]
Deng, Bing [2 ]
Shen, Hongyi [2 ]
Ji, Guang [4 ]
Li, Guowen [3 ]
Xie, Yan [2 ,4 ]
机构：
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Res Ctr Hlth & Nutr, Shanghai 201203, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Hosp, Dept Pharm, Shanghai 200082, Peoples R China
[4] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Digest Dis, Shanghai 200032, Peoples R China
来源：
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2015年 / 80卷
基金：
中国博士后科学基金; 美国国家科学基金会;
关键词：
Phytic acid; Tight junction; Paracellular permeability; Divalent cations; Protein distribution; Protein expression level; EPITHELIAL PERMEABILITY; ABSORPTION; MONOLAYERS; MODULATION; EXPRESSION; OCCLUDIN; CALCIUM; PHOSPHORYLATION; ISORHAMNETIN; ENHANCEMENT;
D O I：
10.1016/j.ejps.2015.09.009
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
This study investigated the effect of phytic acid (IP6), a potential absorption enhancer of flavonoid components, on tight junction (TJ) integrity in Caco-2 cell monolayers and its possible mechanisms. Transepithelial electrical resistance (TEER) across the monolayers decreased rapidly, and the flux of fluorescein sodium (a paracellular marker) increased after treating with IP6 in a concentration-dependent manner. Confocal microscopy results showed that IP6 produced a concentration-dependent attenuation in the distribution of occludin, ZO-1, and claudin-1. Immunoblot analysis revealed that IP6 could down-regulate the expression level of these TJ proteins, which resulted in the opening of TJ. Additionally, the divalent cations Ca2+ and Mg2+ influenced the IP6-induced distribution of occludin, ZO-1, and claudin-1 in different directions, which enhanced barrier function. In conclusion, IP6 can decrease the integrity of Caco-2 cell monolayers by modulating the TJ proteins' localization and down-regulating the expression levels of TJ proteins including claudin-1, occludin, and ZO-1; the reduction effects of divalent cations such as Ca2+ and Mg2+ on the regulation of TJ induced by IP6 should be addressed. The present work will offer some useful guidance for the application of IP6 in drug delivery area. (C) 2015 Elsevier B.V. All rights reserved.
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页码：1 / 8
页数：8
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