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Abstract Title:

16α-Hydroxytrametenolic Acid fromImproves Intestinal Barrier Function Through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway.

Abstract Source:

J Agric Food Chem. 2019 Oct 2 ;67(39):10871-10879. Epub 2019 Sep 23. PMID: 31517482

Abstract Author(s):

Hui Xu, Yuchen Wang, Peter W Jurutka, Shen Wu, Yadong Chen, Chongjiang Cao, Guitang Chen, Bei Tian, Suilou Wang, Shujie Cheng

Article Affiliation:

Hui Xu

Abstract:

This study evaluated the effect of triterpenoids from edible mushroomon intestinal epithelium integrity and revealed the transcriptional regulatory pathways that underpin restorative mechanisms in the gut. Based on computational docking studies, transcriptional activation experiments and glucocorticoid receptor (GR) protein immunofluorescence localization assays in cultured cells, 16α-hydroxytrametenolic acid (HTA) was discovered as a novel GR agonist in this study. HTA ameliorates TNF-α-induced Caco-2 monolayer intestinal epithelial barrier damage and suppressed activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), which attenuated downstream IκB and nuclear factor kappa-B (NF-κB) phosphorylation through GR activation. Moreover, HTA prevented NF-κB translocation into the nucleus and binding to its cis-element and suppressed lipopolysaccharide-induced downstream NO production and pro-inflammatory cytokines at both protein and mRNA expressionlevels. In conclusion, HTA fromimproves intestinal barrier function through a GR-mediated PI3K/Akt/NF-κB signaling pathway and may be potentially exploited as a supportive dietary therapeutic strategy for restoring gut health.

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