Ilex rotunda Thunb Protects Against Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Restoring the Intestinal Mucosal Barrier and Modulating the Oncostatin M/Oncostatin M Receptor Pathway

Abstract

Ilex rotunda Thunb (IR) is a traditional Chinese medicine used for the clinical treatment of gastric ulcers and duodenal ulcers; however, the effect of IR on ulcerative colitis (UC) and its underlying mechanism remains unclear. This study investigated the therapeutic effect of IR on UC mice induced by dextran sulfate sodium (DSS) as well as the potential underlying mechanism. The main components of IR were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Then we established a model of UC mice by administering 2.0% DSS for 7 days followed by 2 weeks of tap water for three cycles and administered IR. On day 56, the disease activity index (DAI), colon length, pathological changes, and inflammatory response of the colon tissue of mice were assessed. The oxidative stress and apoptosis of colon tissue were detected, and the integrity of the intestinal mucosal barrier was evaluated to assess the effect of IR. Furthermore, the relationship between oncostatin M (OSM) and its receptor (OSMR) in addition to the IR treatment of UC were evaluated using a mouse model and Caco2 cell model. The results showed that IR significantly alleviated the symptoms of UC including rescuing the shortened colon length; reducing DAI scores, serum myeloperoxidase and lipopolysaccharide levels, pathological damage, inflammatory cell infiltration and mRNA levels of interleukin one beta, tumor necrosis factor alpha, and interleukin six in colon tissue; alleviating oxidative stress and apoptosis by decreasing kelch-like ECH-associated protein 1 expression and increasing nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase-1 protein expression; and promoting the regeneration of epithelial cells. IR also promoted the restoration of the intestinal mucosal barrier and modulated the OSM/OSMR pathway to alleviate UC. It was found that IR exerted therapeutic effects on UC by restoring the intestinal mucosal barrier and regulating the OSM/OSMR pathway.

Porcine Intestinal Mucosal Peptides Target Macrophage-Modulated Inflammation and Alleviate Intestinal Homeostasis in Dextrose Sodium Sulfate-Induced Colitis in Mice

“…DSS is known to elevate intestinal mucosal permeability, upregulate specific inflammatory factors, and disrupt the balance of intestinal microbiota, triggering inflammation [ 46 ]. Numerous pro- and anti-inflammatory cytokines are important participants in intestinal inflammation [ 47 ]. TNF-α, IL-1β, and IL-6 work together to stimulate the production of adhesion molecules, chemokines, and other cytokines, which in turn promotes inflammation [ 48 ].…”

PVA enema ameliorates DSS-induced acute colitis in mice

“…In instances of UC, augmented apoptotic cell and histiocyte counts within the lamina propria are observed, the latter facilitating phagocytosis of apoptotic cells [ 32 ]. Scholarly discourse highlights the pivotal role of intestinal epithelial cell demise in perpetuating colitis-associated inflammation and compromised barrier integrity [ 33 , 34 ]. The confluence of increased intestinal epithelial cell mortality and heightened inflammatory cell presence precipitates the enduring course of UC.…”

PVA enema ameliorates DSS-induced acute colitis in mice

“…During UC, the lamina propria has more apoptotic cells and histiocytes, the latter of which is used to phagocytose apoptotic cells [31]. Studies have shown that the death of intestinal epithelial cells is responsible for the persistence of in ammation in colitis and impaired barrier function [32,33]. The death of intestinal epithelial cells and the increase of in ammatory cells lead to long-lasting UC.…”