title: The effect of phytic acid on tight junctions in the human intestinal Caco-2 cell line and its mechanism.
abstract: 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.
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qingxue
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Xia
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Deng
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Shen
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China. Electronic address: lgwshutcm@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Li
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: rosexie_1996@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
mesh_terms: D018938:Caco-2 Cells / Q000187:drug effects*; D062445:Claudin-1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007408:Intestinal Absorption / Q000187:drug effects; D018613:Microscopy, Confocal; D062793:Occludin / Q000378:metabolism; D010833:Phytic Acid / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D062793:Occludin; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D010833:Phytic Acid
keywords: Arginine (PubChem CID: 6322); Dimethyl sulfoxide (PubChem CID: 679); Divalent cations; Fluorescein sodium (PubChem CID: 9885981); MTT (PubChem CID: 64966); Methanol (PubChem CID: 887); Paracellular permeability; Paraformaldehyde (PubChem CID: 24754); Phytic acid; Phytic acid (PubChem CID: 890); Protein distribution; Protein expression level; Quercetin (PubChem CID: 5280343); Tight junction; Triton X-100 (PubChem CID: 5590); Tween-20 (PubChem CID: 443314)