Cinobufotalin ameliorates ulcerative colitis by modulating gut microbiota, restoring Th17/Treg balance, and inhibiting MAPK/NF-κB signaling pathways

Ethnopharmacological relevance: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, with symptoms including abdominal pain and bloody stools. The pathogenesis involves immune dysregulation, gut microbiota imbalance, and environmental factors. Current treatments have limitations, prompting the exploration of alternative therapies like traditional Chinese medicine. Cinobufotalin, an indole alkaloid from Bufo gargarizans, shows potential due to its anti-inflammatory and anti-tumor properties.

Materials and methods: A Dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate cinobufotalin's effects. Mice were divided into control, DSS, and cinobufotalin-treated groups. Clinical symptoms, gut microbiota, intestinal permeability, and Th17/Treg balance were assessed. Techniques included H&E staining, RNA extraction, Western blot, flow cytometry, and 16S rRNA Sequencing.

Results: Cinobufotalin alleviated DSS-induced colitis symptoms, restored gut microbiota balance, increased SCFA-producing bacteria, reduced intestinal permeability, and regulated Th17/Treg balance. It also modulated inflammatory cytokine expression by inhibiting the MAPK/NF-κB signaling pathways. Co-housing experiments showed that cinobufotalin's protective effects could be transferred via gut microbiota.

Conclusions: Cinobufotalin demonstrates significant therapeutic potential for UC by modulating gut microbiota, reducing inflammation, and restoring immune balance, likely through the PPARγ pathway. These findings identify cinobufotalin as a promising candidate treatment for UC.

Cinobufotalin; Gut microbiota; Short-chain fatty acids; Th17/Treg balance; Ulcerative colitis.