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

  • Eur J Pharm Sci. 2015 Dec 1:80:1-8. doi: 10.1016/j.ejps.2015.09.009.
Qingxue Fu  1 ,  Huizhen Wang  2 ,  Mengxin Xia  2 ,  Bing Deng  2 ,  Hongyi Shen  2 ,  Guang Ji  3 ,  Guowen Li  4 ,  Yan Xie  5
Affiliations
  • 1. 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.
  • 2. Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 3. Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
  • 4. Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China. Electronic address: [email protected].
  • 5. 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: [email protected].
PMID: 26385515 DOI: 10.1016/j.ejps.2015.09.009
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.

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).
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