Ononin combined with Lactobacillus paracasei alleviates DSS-induced ulcerative colitis by ferroptosis via inhibiting JAK2/STAT3 signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex pathogenesis and limited treatment options. This study aimed to evaluate the therapeutic effect of Ononin combined with Lactobacillus paracasei in a dextran sulfate sodium (DSS)-induced murine UC model and to elucidate the underlying mechanisms involving ferroptosis and the JAK2/STAT3 signaling pathway. A UC model was established by administering 3% DSS in drinking water to male BALB/c mice. Therapeutic efficacy was assessed based on changes in body weight, disease activity index (DAI), colon length, and histopathological alterations. Serum levels of inflammatory cytokines (TNF-α, IL-1β) and oxidative stress markers (MPO, MDA, SOD, GSH) were quantified. Protein expression related to ferroptosis (ACSL4, GPX4), intestinal barrier integrity (Occludin, Claudin-1), and the JAK2/STAT3 pathway was analyzed in colon tissue. Combined treatment with Ononin and Lactobacillus paracasei significantly alleviated UC symptoms, as shown by improved body weight, colon length, DAI scores, and histopathology. It also reduced pro-inflammatory cytokine levels, suppressed oxidative stress and neutrophil infiltration, and enhanced antioxidant capacity. Mechanistically, the treatment downregulated ACSL4 expression, inhibited JAK2/STAT3 phosphorylation, and upregulated the expression of GPX4, Occludin, and Claudin-1. The combination of Ononin and Lactobacillus paracasei effectively ameliorated DSS-induced colitis in mice. Its protective mechanism involves suppressing inflammation and oxidative stress, inhibiting ferroptosis (potentially through blocking the JAK2/STAT3 pathway), and enhancing intestinal barrier integrity. These findings provide a strong preclinical rationale for developing this combination as a potential therapeutic strategy for UC.