Biochanin A and prunetin improve epithelial barrier function in intestinal CaCo-2 cells via downregulation of ERK, NF-κB, and tyrosine phosphorylation

verfasst von

S. Piegholdt, K. Pallauf, T. Esatbeyoglu, N. Speck, K. Reiss, L. Ruddigkeit, A. Stocker, P. Huebbe, G. Rimbach

Abstract

The single-layered gut epithelium represents the primary line of defense against environmental stressors; thereby monolayer integrity and tightness are essentially required to maintain gut health and function. To date only a few plant-derived phytochemicals have been described as affecting intestinal barrier function. We investigated the impact of 28 secondary plant compounds on the barrier function of intestinal epithelial CaCo-2/TC-7 cells via transepithelial electrical resistance (TEER) measurements. Apart from genistein, the compounds that had the biggest effect in the TEER measurements were biochanin A and prunetin. These isoflavones improved barrier tightness by 36 and 60%, respectively, compared to the untreated control. Furthermore, both isoflavones significantly attenuated TNFα-dependent barrier disruption, thereby maintaining a high barrier resistance comparable to nonstressed cells. In docking analyses exploring the putative interaction with the tyrosine kinase EGFR, these novel modulators of barrier tightness showed very similar values compared to the known tyrosine kinase inhibitor genistein. Both biochanin A and prunetin were also identified as potent reducers of NF-κB and ERK activation, zonula occludens 1 tyrosine phosphorylation, and metalloproteinase-mediated shedding activity, which may account for the barrier-improving ability of these isoflavones.

Organisationseinheit(en)

Institut für Lebensmittelwissenschaft und Humanernährung
Molekulare Lebensmittelchemie und -entwicklung

Typ

Artikel

Journal

Free Radical Biology and Medicine

Band

70

Seiten

255-264

Anzahl der Seiten

10

ISSN

0891-5849

Publikationsdatum

05.2014

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Biochemie, Physiologie (medizinische)

Elektronische Version(en)

https://doi.org/10.1016/j.freeradbiomed.2014.02.025 (Zugang: Geschlossen)