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

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.

Pachymic acid inhibits inflammation and cell apoptosis in lipopolysaccharide (LPS)-induced rat model with pneumonia by regulating NF-κB and MAPK pathways

“…11 It could also protect against cerebral ischemia injury by targeting PI3K/Akt pathway. 10 Also, PA enhanced melatonin by inhibition of AKI-to-CKD transition through mediating growth arrest-specific 6 and nuclear factor-erythroid-2-related factor 2 (Gas6/Nrf2) axis. 10 Another study showed that PA impaired glucose metabolism and stimulated mitochondrial apoptosis.…”

“…10 Also, PA enhanced melatonin by inhibition of AKI-to-CKD transition through mediating growth arrest-specific 6 and nuclear factor-erythroid-2-related factor 2 (Gas6/Nrf2) axis. 10 Another study showed that PA impaired glucose metabolism and stimulated mitochondrial apoptosis. 8 In the present study, the alterations of Bax and Bcl-2 were reversed by PA treatment, suggesting that PA suppressed cell apoptosis in rats with lung injury.…”

“…9 Besides, PA protects cardiomyocytes from LPS-induced inflammation and apoptosis by regulating the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways. 10 PA also competitively inhibits the biological activity of phospholipase A2 (PLA2) and reduces PLA2-mediated cell damage. 6 In addition, PA inhibits the invasion of breast cancer by regulating nuclear factor kappa B (NF-κB) pathway.…”

ShenLing BaiZhu San alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota

“…Furthermore, Ginsenoside Rg1, also one of the main constituents of Panax ginseng, and its metabolites could inhibit colitis [15]. 16α-hydroxytrametenolic acid from Poria cocos improved intestinal barrier function [16]. Yam polysaccharide from Dioscorea opposita reduced in ammation in the rat model of colitis induced by TNBS [17].…”

Phytochemistry and Biological Activities of Poria

“…Effects on the Gut.Studies showed that Poria had a protective effect on the intestinal tract. 16α-hydroxytrametenolic acid (6) could improve intestinal barrier function through glucocorticoid receptor-mediated PI3K/ Akt/NF-κB pathway, suggesting that 16α-hydroxytrametenolic acid could strengthen the intestinal barrier[96]. Xiao et al study showed that the alcohol extract of Poria could inhibit intestinal contraction in vitro by blocking the M receptor and regulate intestinal peristalsis function, which provided a new theoretical basis for the treatment of diarrhea type IBS…”