Panaxynol Preserves Gut Architecture, Reduces Colitis-Associated Microbes, and Modulates Immune Response to Alleviate Colitis 9222

Abstract Description Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine affecting millions globally. Current treatments often have off-target effects, highlighting the need for safer, more effective alternatives. This study expands on previous findings that panaxynol, a novel, bioavailable compound in American ginseng, reduces murine colitis severity. Here we investigate the mechanisms through which panaxynol alleviates chronic and acute murine colitis.14-week-old C57BL/6 female mice were given 3 rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or 1 round for acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage 3x/week. Panaxynol significantly (p < 0.05) improved disease activity index and endoscopic scores in both models. In the acute model, panaxynol reduced DSS-induced colonic crypt distortion, goblet cell loss, and mucus depletion.16S sequencing revealed that panaxynol altered microbial composition, suppressing colitis-enriched genera (e.g., Enterococcus, Eubacterium, Ruminococcus). Flow cytometry showed panaxynol significantly repressed macrophage polarization and increased regulatory T-cells in the colonic lamina propria. Panaxynol’s effects on mucosal architecture, microbiota, and immune modulation highlight mechanisms underlying its suppression of murine colitis and its potential as a clinical therapy for colitis. Funding Sources This work was funded by NIH R01CA246809, U01CA272977, and F31AT012589. Topic Categories Mucosal and Regional Immunology (MUC)