The potential mechanism of co-administration of Scutellaria baicalensis Georgi and Rubia cordifolia L ameliorating ulcerative colitis: Integration of metabolomics, network pharmacology, and molecular docking.

Scutellaria baicalensis Georgi (HQ) and Rubia cordifolia L. (QC) are clinically effective against ulcerative colitis (UC), but their synergistic mechanisms remain unclear. This study evaluated the therapeutic effects of HQ, QC, and their combination (HQ-QC) in dextran sulfate sodium (DSS)-induced colitis and explored underlying mechanisms. Mice were divided into normal, model, HQ, QC, HQ-QC, and 5-ASA groups. Colon tissue metabolomics was performed using UPLC-Q-TOF-MS, while network pharmacology and molecular docking identified potential anti-UC targets. The HQ-QC combination significantly alleviated weight loss, colon shortening, and histopathological damage, and improved intestinal barrier function and inflammation compared to single herbs. Metabolomics revealed xanthine, cytosine, and N-octanoylsphingosine-1-phosphate as key metabolites enriched in vascular smooth muscle contraction and fatty acid metabolism pathways. Network pharmacology identified 62 potential targets, with wogonin and xyloidone as major active compounds. KEGG analysis highlighted platelet activation as a key pathway, and molecular docking confirmed strong binding of wogonin and xyloidone to platelet activation-related targets including PIK3CG, NOS3, PTGS1, and MAPK14. These findings suggest HQ-QC exerts synergistic effects in treating DSS-induced UC by regulating vascular smooth muscle contraction and platelet activation, providing mechanistic insight into its clinical potential.