TY - JOUR

T1 - Biochanin A and prunetin improve epithelial barrier function in intestinal CaCo-2 cells via downregulation of ERK, NF-κB, and tyrosine phosphorylation

AU - Piegholdt, S.

AU - Pallauf, K.

AU - Esatbeyoglu, T.

AU - Speck, N.

AU - Reiss, K.

AU - Ruddigkeit, L.

AU - Stocker, A.

AU - Huebbe, P.

AU - Rimbach, G.

N1 - Funding information: Karina Reiss and Gerald Rimbach are supported by the DFG Cluster of Excellence “Inflammation at Interfaces.” Patricia Huebbe, Karina Reiss and Gerald Rimbach are supported by the DFG Research Training Group 1743 “Genes, Environment and Inflammation.”

PY - 2014/5

Y1 - 2014/5

N2 - 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.

AB - 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.

KW - Biochanin A

KW - ERK

KW - Intestinal epithelial barrier

KW - Isoflavones

KW - NF-κB

KW - Prunetin

KW - Tyrosine phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=84898402102&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2014.02.025

DO - 10.1016/j.freeradbiomed.2014.02.025

M3 - Article

VL - 70

SP - 255

EP - 264

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -