Isorhamnetin ameliorates active ulcerative colitis potentially involving the Nrf2-PTGS2 axis: an integrative study from clinical evidence mining to in vivo validation

Ulcerative colitis (UC) is a worldwide health issue with limited therapies. Traditional Chinese Medicine (TCM) shows potential, but lacks systematic efficacy evaluation and detailed mechanistic explanations. This study aims to evaluate the efficacy of TCM for active UC and explore its mechanisms. A meta-analysis of RCTs was conducted to assess TCM efficacy in active UC, and treatment efficacy was ranked. Core Chinese herbs were identified via association rule analysis. Network pharmacology and molecular docking predicted active components, targets, and pathways. Efficacy of the key component was validated in active UC mice. 17 studies (1,598 patients) showed TCM significantly improved active UC (SMD -1.73, 95%CI -2.21 to -1.25). Eight core Chinese herbs were identified. Network pharmacology revealed 76 overlapping targets. Isorhamnetin (Iso) showed strong binding to PTGS2 (binding energy: -9.34 kcal/mol) and Nrf2 (binding energy: -9.16 kcal/mol). In vivo, Iso dose-dependently alleviated disease symptoms, pathological damage, and spleen index in UC mice. TCM could ameliorate active UC. The key active component Iso shows therapeutic effects, with mechanisms potentially involving the Nrf2-PTGS2 axis and immune-inflammatory pathways. The findings offer some insight into the scientific basis of TCM in treating UC and predict that Iso may be a candidate for further mechanistic and clinical investigation.