16α-Hydroxytrametenolic Acid from Poria cocos Improves Intestinal Barrier Function through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway

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

Research output: Contribution to journalArticle

Abstract

This study evaluated the effect of triterpenoids from edible mushroom Poria cocos on 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 expression levels. In conclusion, HTA from P. cocos improves 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.

Original languageEnglish (US)
Pages (from-to)10871-10879
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume67
Issue number39
DOIs
StatePublished - Oct 2 2019

Fingerprint

Wolfiporia cocos
Phosphatidylinositol 3-Kinase
NF-kappa B
Glucocorticoid Receptors
phosphatidylinositol 3-kinase
Acids
Chemical activation
acids
digestive system
Proto-Oncogene Proteins c-akt
Phosphorylation
Agaricales
transcriptional activation
Intestinal Mucosa
intestinal mucosa
triterpenoids
protein kinases
mushrooms
cultured cells
lipopolysaccharides

Keywords

  • 16α-hydroxytrametenolic acid
  • glucocorticoid receptor
  • intestinal barrier
  • PI3K/Akt/NF-κB pathway
  • Poria cocos
  • triterpenoids

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

16α-Hydroxytrametenolic Acid from Poria cocos Improves Intestinal Barrier Function through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway. / Xu, Hui; Wang, Yuchen; Jurutka, Peter W.; Wu, Shen; Chen, Yadong; Cao, Chongjiang; Chen, Guitang; Tian, Bei; Wang, Suilou; Cheng, Shujie.

In: Journal of Agricultural and Food Chemistry, Vol. 67, No. 39, 02.10.2019, p. 10871-10879.

Research output: Contribution to journalArticle

Xu, Hui ; Wang, Yuchen ; Jurutka, Peter W. ; Wu, Shen ; Chen, Yadong ; Cao, Chongjiang ; Chen, Guitang ; Tian, Bei ; Wang, Suilou ; Cheng, Shujie. / 16α-Hydroxytrametenolic Acid from Poria cocos Improves Intestinal Barrier Function through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway. In: Journal of Agricultural and Food Chemistry. 2019 ; Vol. 67, No. 39. pp. 10871-10879.
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