Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 80, Issue -, Pages 1-8Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2015.09.009
Keywords
Phytic acid; Tight junction; Paracellular permeability; Divalent cations; Protein distribution; Protein expression level
Categories
Funding
- National Science Foundation of China [81303304]
- Shanghai Municipal Education Commission [14YZ057]
- Specialized Research Fund for Doctoral Program of Higher Education [20133107120006]
- China Postdoctoral Science Foundation [2015 M571596]
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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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