Anti-inflammatory activity and mechanism of action of Banxia Xiexin Decoction on DSS-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD) is a Traditional Chinese Medicine (TCM) formulation, historically utilized in the treatment of ulcerative colitis (UC). However, its precise active constituents and the underlying mechanisms of action remain insufficiently understood.

AIM OF THE STUDY: We herein aimed to explore the molecular mechanisms by which BXD mitigates dextran sodium sulfate (DSS)-induced UC in mice.

MATERIALS AND

METHODS

Ultra-performance liquid chromatograph-hybrid quadrupole orbitrap high resolution mass spectrometry, network pharmacology and molecular docking were employed to identify active compounds and possible targets of BXD in UC. The protective impact of BXD treatment of DSS-stimulated UC in mice was assessed via analysis of pathological alterations and their mitigation. Pro-inflammatory cytokine levels were determined using an enzyme-linked immunosorbent assay. RNA sequencing (RNA-seq) was employed to explore the mechanism(s) underlying BXD activity in UC. The related pathway protein expression was evaluated by immunohistochemistry.

RESULTS

We first analyzed serum samples and detected 15 prototype chemical components from BXD. Database searches identified 271 genes as being correlated with these 15 prototype chemical components in BXD and 1519 genes associated with UC. We observed that oral BXD treatment ameliorated UC symptoms in mice, reducing weight loss, colon shortening, mucosal epithelium damage, and inflammation, while increasing goblet cell-mediated mucous production. Furthermore, BXD treatment repressed tumor necrosis factor-α, interleukin-6, and interleukin-1-β levels in the serum of mice. RNA-seq and comprehensive network pharmacology analyses revealed a significant enrichment of nuclear factor kappa B (NF-κB) pathways. Mechanistically, BXD treatment potently suppressed activation of the inhibitor of kappa B kinase (IκK)/inhibitor of NF-κB (IκB)/NF-κB pathway.

CONCLUSION

These findings suggest that BXD may attenuate the pro-inflammatory response and alleviate symptoms of UC by modulating the IκK/IκB/NF-κB pathway. Hence, we identify a potential pharmaceutical candidate and an innovative therapeutic approach for UC intervention.