Ulcerative colitis (UC) is a chronic inflammatory bowel disease related to intestinal dysbiosis. Sanguinarine chloride hydrate (SGCH), the hydrochloride form of sanguinarine (SG), which constitutes the principal constituents of Macleaya cordata, exhibits diverse biological and pharmacological activities. Previous studies have demonstrated that SG can ameliorate UC in murine models by modulating the inflammatory pathways. However, the precise molecular mechanistic underlying the therapeutic efficacy of SGCH, as well as its impact on gut microbiota and short-chain fatty acids (SCFAs), remain elusive. Therefore, this study investigated the effects of SGCH on the pathological symptoms, the mRNA expression levels of inflammatory cytokines, colonic mucosal barrier damage, microbiota composition, and SCFAs metabolism in dextran sulfate sodium (DSS)-induced UC mice. The administration of SGCH can ameliorate clinical symptoms in UC mice, partially restore colon length and colonic epithelial cell morphology, regulate mRNA expression levels of inflammatory cytokines and tight junction proteins associated with UC. Further studies revealed that SGCH effectively reversed the decrease in intestinal microbiota diversity induced by UC, thereby promoting the growth of beneficial bacteria such as Colidextribacter, Akkermansia, Alistipes, and norank_o__Clostridia_UCG-014. Correlation analysis demonstrated a positive association between butanoic acid, propanoic acid, isobutyric acid, isovaleric acid, valeric acid, hexanoic acid with Colidextribacter, while Coriobacteriaceae_UCG-002 exhibited a negative correlation with butanoic acid, acetic acid and propanoic acid. SGCH alleviates DSS-induced colitis by modulating intestinal microbiota metabolism and SCFAs production.
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