Trifolirhizin regulates the balance of Th17/Treg cells and inflammation in the ulcerative colitis mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome.

Ulcerative colitis (UC) is a chronic and recurrent autoimmune disease, characterized by recurrence and remission of mucosal inflammation. Although the understanding of the pathogenesis of UC has been improved, effective therapeutic drugs are required for treating patients with UC. In current work, the mouse model of colitis was established. Trifolirhizin was demonstrated to improve symptom in dextran sulfate sodium (DSS)-induced colitis mice. The body weight of mice was elevated, whereas the disease activity index (DAI) was reduced. Moreover, trifolirhizin was involved in inhibition of inflammation and regulation of the balance of T helper 17 (Th 17) cells and regulatory T (Treg) cells in DSS-induced colitis mice. Further, the activation NLRP3 inflammasome was suppressed by trifolirhizin in DSS-induced colitis mice. Trifolirhizin was also identified to regulate AMP-activated protein kinase (AMPK)-thioredoxin-interacting protein (TXNIP) pathway. The trifolirhizin-mediated anti-inflammatory effect was inhibited by suppressing AMPK in DSS-induced UC mice. In summary, the research suggested that administration of trifolirhizin significantly improved the symptoms and the pathological damage in DSS-induced UC mice. Trifolirhizin regulated the balance of Th17/Treg cells and inflammation in the UC mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome.

Momordica charantia polysaccharides alleviate diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and barrier via NF-κB pathway.

BACKGROUND: Momordica charantia exerts anti-inflammatory effect against ulcerative colitis. Momordica charantia polysaccharides (MCPs) attenuate gastritis through inhibition of ethanol-induced inflammatory response. OBJECTIVE: The role of MCPs in diarrhea-predominant irritable bowel syndrome (IBS-D) is investigated. MATERIALS AND METHODS: Chemical stimulation followed by acute and chronic pressure stimulation was used to establish rats model with IBS-D. The model rats were then administrated with MCPs. Defecation frequency, fecal water content and abdominal withdrawal reflex (AWR) score were then recorded. Pathologic changes in the colonic tissues were evaluated by hematoxylin and eosin staining. Inflammation was detected by ELISA and qRT-PCR, and immunohistochemistry was used to assess intestinal mucosal permeability. RESULTS: First, IBS-D of mice wasIBS-D ratsmice exhibited many abnormal clinical manifestations, including increased frequency of defecation, fecal water content, and abdominal withdrawal reflex (AWR) score. Second, the mice were administrated with MCPs, which reduced frequency of defecation, fecal water content, and AWR score, and 100-mg/kg MCPs indicated therapeutic effect on IBS-D mice equivalent to rifaximin. Moreover, MCPs also ameliorated pathologic changes in the colonic tissues of IBS-D mice. Third, inflammatory response in IBS-D mice was also suppressed by MCPs through up-regulation of Interleukin (IL)-10, and down-regulation of tumor necrosis factor-α (TNF-α), Interleukin(IL)-1ß, and IL-6. MCPs enhanced levels of occludin (OCLN) and zona occludens protein-1 (ZO-1) in IBS-D mice to improve intestinal mucosal permeability. Finally, phosphorylation of p65 in IBS-D mice was reduced by MCP treatment. CONCLUSION: MCPs ameliorated intestinal permeability and repressed intestinal inflammation to attenuate IBS-D by inactivating nuclear factor kappa B (NF-κB) signaling.