Prim-O-glucosylcimifugin ameliorates DSS-induced ulcerative colitis via suppressing NLRP3 inflammasome activation

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease (IBD), that lacks specific therapeutic drugs. Prim-O-glucosylcimifugin (POG), a furanochromone glycoside derived from Saposhnikovia divaricata, exhibits anti-inflammatory, antioxidant, and anti-inflammasome activities. It has also been shown to inhibit the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Given that ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by intestinal barrier dysfunction and NLRP3 activation, this study aims to investigate the therapeutic effects and underlying mechanisms of POG in a murine model of UC induced by dextran sulfate sodium (DSS), and to evaluate its potential translational significance for UC intervention.

A DSS-induced UC mouse model was employed to evaluate POG's therapeutic efficacy. Disease activity index, colon length, spleen index, and histopathological alterations of the colonic mucosa were assessed by H&E and AB-PAS staining, transmission electron microscopy, and immunofluorescence. Proinflammatory cytokines (TNF-α, IL-6, IL-18, IL-1β) were measured by ELISA, and NLRP3 inflammasome-related proteins were analyzed by Western blot.

POG treatment alleviated weight loss, colon shortening, splenomegaly, and inflammatory infiltration. It also restored goblet cell mucin droplets and tight junction proteins (Occludin, ZO-1, Claudin-1, MUC2), and reduced villi exfoliation. Serum levels of TNF-α, IL-6, IL-1β, and IL-18 were decreased. Western blot and ELISA revealed that POG suppressed NLRP3 inflammasome formation, inhibited GSDMD activation, and reduced cleavage and release of IL-1β and IL-18. Collectively, these findings indicate that POG not only attenuates inflammatory injury but also protects epithelial barrier structure and function, supporting its potential value in mechanism-based UC therapy development.

POG ameliorates experimental UC by inhibiting NLRP3 inflammasome activation, thereby mitigating colonic inflammation, preserving mucosal barrier integrity, and blocking downstream inflammatory responses. POG shows promise as a therapeutic agent for UC and provides a rationale for further preclinical optimization and future clinical translation.