Maqian (Zanthoxylum myriacanthum var. pubescens) bark extract alleviates DSS-induced colitis via dual TLR4/NF-κB inhibition and intestinal barrier restoration

Ulcerative colitis (UC) prevalence is increasing in Asia, with limited treatment options. Increasing treatment needs for UC warrant exploration of ethnopharmacological resources. This study validated the ethnopharmacological application of the bark of Zanthoxylum myriacanthum var. pubescens (Maqian) (MQEB) for gastrointestinal inflammation by evaluating its dual mechanisms against UC pathogenesis. In vitro analyses employed lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and Caco-2 intestinal epithelial cells treated with MQEB (10–40 μg/mL), quantifying cytokine profiles via enzyme-linked immunosorbent assay (ELISA). In vivo studies utilized dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice administered oral MQEB (125, 250, or 500 mg/kg) or salicylazosulfapyridine (SAL, 300 mg/kg), with assessments of disease activity index (DAI), histopathology, tight junction protein expression, and toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway modulation. MQEB significantly attenuated colitis severity through dose-dependent suppression of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-17), inhibition of TLR4/NF-κB signaling, and restoration of intestinal barrier integrity via upregulation of tight junction proteins (zona occludens-1 (ZO-1), Claudin5). Safety assessments confirmed absence of hepatorenal toxicity, supporting MQEB as a multi-target botanical therapeutic for UC. • This study Provides systematic evidence for Maqian bark extract treating ulcerative colitis, linking traditional use with modern mechanisms. • Exerts dual effects: suppresses inflammation via TLR4/NF-κB inhibition and enhances intestinal barrier via tight junction proteins. • Identifies 54 bioactive constituents (e.g., lignans, alkaloids), suggesting synergistic therapeutic actions of multiple compounds. • High-dose extract (500 mg/kg) alleviates colitis comparably to sulfasalazine, reducing disease activity and colon shortening. • Safety assessments confirm no hepatorenal toxicity within tested dosages, supporting its potential for clinical development.