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

The Danggui-Baishao herb pair improved key colitis parameters in a DSS-induced mouse model.

• A mouse model of colitis was induced by administering 2.5% dextran sulfate sodium.
• Treatment with the herb pair improved body weight, colon length, intestinal inflammation, and barrier function.
• Histopathological analysis was used to evaluate therapeutic effects alongside body weight changes and colon length measurements.

The Danggui-Baishao herb pair upregulated intestinal stem cell markers and proliferation-related proteins.

• The herb pair upregulated expression of the intestinal stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5).
• Proliferation-related proteins were also upregulated following herb pair treatment.
• These findings suggest the herb pair supports intestinal epithelial regeneration.

RNA sequencing analysis revealed that the Danggui-Baishao herb pair activated the Wnt/β-catenin signaling pathway.

• RNA sequencing was utilized to investigate the underlying mechanisms of the herb pair's anti-colitis effects.
• The Wnt/β-catenin signaling pathway was identified as activated by the herb pair treatment.
• Following intraperitoneal injection of the β-catenin antagonist ICG-001, the therapeutic efficacy of the herb pair was diminished, confirming pathway dependency.

Metabolomic analysis revealed that the Danggui-Baishao herb pair altered bile acid composition.

• Metabolomic analysis was conducted to investigate underlying mechanisms.
• The herb pair treatment resulted in changes in bile acid composition in the DSS-induced colitis model.

The Danggui-Baishao herb pair modulated gut microbiota with enrichment of probiotics and depletion of pathogenic bacteria.

• 16S rRNA sequencing and metagenomic sequencing were used to characterize gut microbiota changes.
• The herb pair treatment resulted in enrichment of probiotics.
• Pathogenic bacteria were depleted following herb pair treatment.

Benzoylpaeoniflorin was identified as a key active component that binds to β-catenin and activates the Wnt/β-catenin signaling pathway.

• Molecular docking showed that benzoylpaeoniflorin can bind to β-catenin.
• In vitro experiments using DSS-treated HCT 116 cells demonstrated that benzoylpaeoniflorin activated the Wnt/β-catenin signaling pathway.
• The therapeutic efficacy of benzoylpaeoniflorin was diminished by ICG-001 treatment in vitro, confirming mechanism specificity.
• The chemical composition of the herb pair was characterized by high performance liquid chromatography-quadrupole/time of flight mass spectrometry analysis.