Extraction Matrix Shapes the Efficacy of Gegen Qinlian Decoction in DSS-Induced Colitis: A Preclinical Systematic Review and Meta-Analysis.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease marked by mucosal injury and immune dysregulation. Gegen Qinlian Decoction (GQD) shows therapeutic potential, but extraction-dependent reproducibility remains unclear. Methods: We systematically searched PubMed, Scopus, and Web of Science for studies evaluating GQD aqueous decoctions or ethanolic extracts in DSS-induced colitis. Main outcome: Disease Activity Index (DAI). Key additional outcomes: colon length and histological injury; cytokines and microbiota were also assessed. Random-effects models with Hartung-Knapp-Sidik-Jonkman adjustment, subgroup analyses, and exploratory dose-response meta-regression were applied. Results: Eight studies were included (aqueous: 5; ethanolic: 3; 209 mice). GQD significantly improved DAI (SMD -2.17; p < 0.00001; I2 = 43%), colon length (MD 1.18 cm; p < 0.00001; I2 = 88%), and histological injury (SMD -3.02; p < 0.0001; I2 = 51%). For DAI, both preparations favored GQD, with absent heterogeneity in aqueous studies (I2 = 0%) vs. substantial variability in ethanolic extracts (I2 = 75%). For histology, subgroup differences suggested a larger effect size with ethanolic extracts, with higher heterogeneity (I2 = 60% vs. 0%). In the aqueous subset, GQD reduced inflammatory markers and increased microbial diversity. Dose-response meta-regression was performed within the aqueous subset as an exploratory analysis. Conclusions: Aqueous decoctions showed the most reproducible profile across key endpoints, whereas ethanolic extracts were more variable despite a larger histology point estimate, indicating that the extraction matrix meaningfully influences translational consistency in preclinical research.