LAUSR

Pectic polysaccharides (PP) could exert functions on ulcerative colitis (UC), which is classified as a non-specific inflammatory disorder. This study investigated the molecular mechanism of PP derived from Rauwolfia in UC. Firstly, the dextran sodium sulfate (DSS)-induced mouse colitis models and lipopolysaccharide (LPS)-treated colonic epithelial cell (YAMC) models were established and treated with PP. Subsequently, the effects of PP on mucosal damages in DSS mice were detected, and the levels of inflammatory cytokines, pyroptosis-related factors, oxidative stress-related markers, and the tight junction-related proteins in the tissues or cells were examined, and the results suggested that PP ameliorated colonic mucosal damages and cell pyroptosis in DSS mice, and limited colonic epithelial cell pyroptosis in vitro UC models. Subsequently, the binding relations of retinol-binding protein 4 (RBP4) to miR-124-3p and NLR pyrin domain containing 3 (NLRP3) were analyzed. miR-124-3p targeted RBP4 and reduced the binding of RBP4 to NLRP3, thus inhibiting NLRP3-mediated pyroptosis. Finally, functional rescue experiments revealed that miR-124-3p suppression or RBP4 overexpression promoted colonic epithelial cell pyroptosis. Collectively, Rauwolfia-derived PP limited miR-124-3p and targeted RBP4, and reduced the binding potency of RBP4 to NLRP3 to inhibit NLRP3-mediated pyroptosis, resulting in the alleviation of colonic epithelial cell pyroptosis and mucosal damages in UC.