STAT3 and colitis: Critically, the mechanism was confirmed to be JAK2-dependent in vitro; experiments demonstrated that JAK2 overexpression alone was sufficient to induce pathology and that it completely reversed the therapeutic effects of matrine.<h4>Conclusion</h4>This study is the first to comprehensively demonstrate that matrine directly targets the JAK2/STAT3 signaling axis to restore bile acid homeostasis and suppress inflammation in experimental colitis with validation in human UC patients, providing novel mechanistic and translational insight into how matrine may benefit colitis.