Protective Effect of Flavonoids in Ulcerative Colitis: A Systematic Review and Meta‐Analysis of Preclinical Studies

The clinical management of ulcerative colitis (UC) remains a significant challenge in modern gastroenterology. Flavonoids have emerged as promising therapeutic candidates due to their broad spectrum of pharmacological activities; however, their precise efficacy in the treatment of UC has yet to be substantiated by systematic clinical evidence. This study conducted a systematic review and meta-analysis to comprehensively evaluate the therapeutic effects of flavonoids in animal models of UC and their potential mechanisms of action. A comprehensive literature search and screening process was conducted across the PubMed, Web of Science, and Embase databases, covering the period from database inception to August 1, 2024. The SYRCLE risk of bias assessment tool was utilized to evaluate the methodological quality of the included studies. Data analysis was performed using STATA 15.1 software, and a time-dose response model was applied to explore the potential dose-response relationship between flavonoid administration and UC outcomes. Ultimately, 33 studies involving a total of 600 experimental animals were included in the analysis. The overall results demonstrated that flavonoids significantly reduced DAI, HS, MPO, MDA, TNF-α, IL-1β, IL-6, iNOS, COX-2, and Spleen Index, while markedly increasing body weight, CL, SOD, GSH, CAT, IL-10, ZO-1, and occludin levels. Time-dose effect analysis revealed that within the dose range of 3.2-400 mg/kg, a significantly enhanced therapeutic outcome can be achieved when combined with an intervention period of 3 to 49 days. Therefore, flavonoids may exert protective effects against UC through anti-inflammatory and antioxidant mechanisms, as well as by modulating intestinal barrier function and gut microbiota. However, the efficacy and safety of flavonoids in treating UC require further validation through extensive clinical trials.