Danggui-Baishao herb pair protects against dextran sulfate sodium-induced colitis by modulating the Wnt/β-catenin pathway.

BACKGROUND: The Danggui-Baishao herb pair is the foundation of a traditional Chinese medicine formula known as Shaoyao decoction, which is widely used in the treatment of colitis. AIM: To uncover the mechanisms underlying the anti-colitis effects of the Danggui-Baishao herb pair. METHODS: The chemical composition of the herb pair was characterized by high performance liquid chromatography-quadrupole/time of flight mass spectrometry analysis. A mouse model of colitis was induced by administering 2.5% dextran sulfate sodium. The therapeutic effects of the herb pair were evaluated based on body weight changes, colon length, histopathological, intestinal inflammation, and barrier function. To investigate the underlying mechanisms, RNA sequencing, metabolomics, 16S rRNA sequencing, metagenomics, and the β-catenin inhibitor ICG-001 were utilized. Furthermore, molecular docking and dextran sulfate sodium-treated HCT 116 cells were conducted to explore the protective mechanisms of benzoylpaeoniflorin. RESULTS: The herb pair improved body weight, colon length, intestinal inflammation, and barrier function. Additionally, the herb pair upregulated the expression of intestinal stem cells marker leucine-rich repeat-containing G-protein coupled receptor 5 and proliferation-related proteins. RNA sequencing analysis showed that the herb pair activated the Wnt/β-catenin signaling pathway. Metabolomic analysis revealed changes in bile acids composition. Through 16S rRNA and metagenomic sequencing, it was observed that the herb pair modulated the gut microbiota, with an enrichment of probiotics and a depletion of pathogenic bacteria. Following intraperitoneal injection of antagonist ICG-001, the therapeutic efficacy was diminished. Molecular docking showed that benzoylpaeoniflorin can bind to β-catenin. Furthermore, benzoylpaeoniflorin can activated the Wnt/β-catenin signaling pathway and the therapeutic efficacy was also diminished by the ICG-001 in vitro. CONCLUSION: The herb pair effectively reduces colonic inflammation and maintains the integrity of the intestinal barrier. Moreover, the anti-colitis efficacy of the herb pair is closely associated with activation of the Wnt/β-catenin pathway.