Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.

BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism. METHODS: CD animal models were created using Il-10-/- mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed. RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10-/- mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10-/- mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10-/- mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10-/- mice, and transplantation of feces from AA-treated mice improved CD-like colitis. CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.

[Protective role of green tea polyphenols in intestinal mucosal barrier function of mice with colitis induced by TNBS through inhibiting JAK2/STAT3 pathway].

Objective To analyze the therapeutic effect of green tea polyphenols (GTP) in mice with colitis induced by TNBS and its possible mechanism. Methods Colitis was induced by TNBS in BALB/C mice. The mice were randomly divided into GTP group (n=10) and TNBS model group (n=10). Mice in the GTP group were given GTP [0.2 mL at a dose level of 100 mg/(kg.d)] by oral gavage, and mice in the model group were given normal saline [0.2 ml/d] by gavage. Four weeks later, the mice were sacrificed. Disease activity index (DAI) and inflammatory score were evaluated by HE staining. The levels of interleukin 10 (IL-10), IL-6 and tumor necrosis factor α (TNF-α) were detected by ELISA. The expressions and localization of ZO-1 and claudin-1 were identified with immunofluorescence technique. Western blot analysis was performed to detect the expressions of ZO-1, claudin-1, p-JAK2 and p-STAT3 proteins. Results GTP decreased the DAI and inflammatory score, and reduced the levels of TNF-α and IL-6 in TNBS-induced colitis mice at three and four weeks after the administration. Meanwhile, the levels of ZO-1 and claudin-1 increased in the mice of GTP group when compared with those in model group. Western blot analysis showed that GTP down-regulated the JAK2/STAT3 signaling pathway in the intestinal mucosa. Conclusion GTP has a significant therapeutic effect on TNBS-induced colitis through down-regulating the JAK2/STAT3 signaling pathway.