Icariin and its phosphorylated derivatives alleviate intestinal epithelial barrier disruption caused by enterotoxigenic Escherichia coli through modulate p38 MAPK in vivo and in vitro

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractThe natural product icariin (ICA) and its phosphorylated derivatives (pICA) have been shown to have outstanding anti-inflammatory and antioxidant properties. This study was to explore the protective effects of ICA and pICA on the intestinal epithelium of enterotoxigenic Escherichia coli (ETEC)-induced piglet diarrhea and its underlying mechanisms in vivo and in vitro. ETEC K88 increased pro-inflammatory cytokine expression, activated oxidative stress and inhibited antioxidant enzyme activity, induced phosphorylated p38 MAPK gene and protein expression, disrupted intestinal barrier function, and led to diarrhea in piglets. Pretreatment with ICA and pICA effectively alleviated ETEC-induced intestinal barrier dysfunction in vivo and in vitro. Pretreatment with p38 MAPK inhibitor (SB203580) significantly rescued the IPEC-J2 cells barrier function damaged by ETEC challenge. However, pretreatment with p38 MAPK activator (anisomycin) did not alleviated the IPEC-J2 cells barrier function damaged by ETEC challenge. Our data demonstrated that ICA and pICA regulate the inflammatory response and oxidative stress of intestinal epithelial cells by inhibiting the expression of p38 MAPK, thereby alleviating ETEC K88-induced disruption of intestinal barrier function and intestinal permeability. These findings provide new insights into the prevention and treatment of intestinal barrier dysfunction induced by ETEC K88. K E Y W O R D S enterotoxigenic Escherichia coli K88, icariin, intestinal barrier function, p38 MAPK, phosphorylated icariin 1784 | XIONG et al.

Clostridium butyricum Protects IPEC‐J2 Cells from ETEC K88‐Induced Oxidative Damage by Activating the Nrf2/ARE Signaling Pathway

“…It combines with the microvilli of intestinal epithelial cells and with receptors on the surface of cells through various types of fimbriae adhesins; then, it propagates in large numbers, which releases enterotoxin, a protein that induces diarrhea [3]. Studies con-ducted on piglet intestinal epithelial cells have shown that ETEC K88-activated oxidative stress destroys the intestinal epithelial barrier and increases permeability, which eventually leads to diarrhea [4]. In addition to piglets, ETEC K88 can activate oxidative stress in mice [5,6].…”

Icariin Alleviates Bisphenol A Induced Disruption of Intestinal Epithelial Barrier by Maintaining Redox Homeostasis In Vivo and In Vitro

“…Previous studies have shown that ICA can significantly alleviate intestinal injury induced by LPS, suggesting that ICA may have an outstanding protective effect on intestinal epithelium. 26 , 27 …”

N‐(3‐oxododecanoyl)‐l‐homoserine lactone disrupts intestinal epithelial barrier through triggering apoptosis and collapsing extracellular matrix and tight junction

“…Our data exhibited that 3OC12 and 3OC14 can induce a loss of mitochondrial membrane potential in intestinal epithelial cells and severe apoptosis. There is an evidence that the activation of oxidative stress is strongly associated with the development of intestinal epithelial barrier dysfunction, primarily due to the ability of oxidative stress to disrupt TJs (Xiong et al, 2020). In the present study, we employed NAC, a powerful antioxidant, to investigate the potential mechanism by which QS autoinducer disrupt the intestinal epithelial barrier.…”