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

Purpose This study aimed to assess the efficacy of Ononin combined with Lactobacillus paracasei in treating dextran-sulfate sodium (DSS)-induced UC, and to investigate some of its underlying mechanisms. Methods BALB/c male mice were given 3% (w/v) DSS to induce ulcerative colitis. Assessments included changes in body weight, disease activity index (DAI), and colon length. The effects of Ononin combined with Lactobacillus paracasei on UC were evaluated by Hematoxylin and eosin (H&E) staining, ELISA, and Western blot. Results The UC models were established successfully by drinking DSS water. Ononin combined with Lactobacillus paracasei showed a significant effect against UC by the increased body weight and colon length, decreased DAI and alleviated histopathological changes. Meanwhile, compared with the DSS group, the inflammation indexes TNF-α, IL-1β and MPO, MDA levels were reduced, while the SOD and GSH levels were increased dramatically . The protein level of ACSL4 and JAK2/STAT3 were obviously downregulated, but the GPX4, Occludin and Claudin-1 expression were upregulated. Conclusion Ononin combined with Lactobacillus paracasei inhibits DSS-induced inflammation, enhances intestinal barrier function, and effectively ameliorates inflammatory injury in UC. These data revealed that suppressing ferroptosis and oxidative stress could effectively ameliorate DSS-induced UC involved in blocking JAK2/STAT3 signaling pathway.