title: Biochanin A and prunetin improve epithelial barrier function in intestinal CaCo-2 cells via downregulation of ERK, NF-κB, and tyrosine phosphorylation.
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.
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, D-24118 Kiel, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Piegholdt
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, D-24118 Kiel, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Pallauf
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, D-24118 Kiel, Germany.
authors.forename: Tuba
authors.initials: T
authors.lastname: Esatbeyoglu
authors.affiliation: Department of Dermatology and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Speck
authors.affiliation: Department of Dermatology and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Reiss
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Ruddigkeit
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Stocker
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, D-24118 Kiel, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Huebbe
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, D-24118 Kiel, Germany. Electronic address: rimbach@foodsci.uni-kiel.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007529:Isoflavones / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D007529:Isoflavones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C083295:prunetin; D014443:Tyrosine; D019833:Genistein; C004541:biochanin A
keywords: Biochanin A; ERK; Intestinal epithelial barrier; Isoflavones; NF-κB; Prunetin; Tyrosine phosphorylation