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

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• 作者：Qingxue Fu^a ; ^b ; Huizhen Wang^b ; Mengxin Xia^b ; Bing Deng^b ; Hongyi Shen^b ; Guang Ji^d ; Guowen Li^c ; ^{lgwshutcm@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yan Xie^b ; ^d ; ^{rosexie_1996@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Phytic acid (PubChem CID ; 890) ; Fluorescein sodium (PubChem CID ; 9885981) ; MTT (PubChem CID ; 64966) ; Dimethyl sulfoxide (PubChem CID ; 679) ; Triton X-100 (PubChem CID ; 5590) ; Paraformaldehyde (PubChem CID ; 24754) ; Methanol (PubChem CID ; 887) ; Tween-20 (PubChem CID ; 443314) ; Arginine (PubChem CID ; 6322) ; Quercetin (PubChem CID ; 5280343)
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2015
• 出版时间：1 December 2015
• 年：2015
• 卷：80
• 期：Complete
• 页码：1-8
• 全文大小：898 K

文摘

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 Ca^2 + and Mg^2 + 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 Ca^2 + and Mg^2 + 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.