KuiAnNingFang alleviates ulcerative colitis by modulating gut microbiota and NF-κB/NLRP3 pathway.

Abstract

BACKGROUND: Ulcerative colitis (UC), a major form of inflammatory bowel disease, is a chronic and relapsing inflammatory condition of the colonic mucosa. Despite the efficacy of the Traditional Chinese Medicine formula KuiAnNingFang (KANF) in alleviating UC, its therapeutic mechanisms remain incompletely understood. PURPOSE: This study aimed to elucidate the ameliorative effect of Chinese medicine KANF and its potential mechanism against UC. METHODS: The therapeutic efficacy of KANF against UC was initially assessed in clinical cohorts. A murine model of UC was subsequently established by administering DSS in drinking water and oral treatment with KANF extracts. The prototype components of KANF absorbed into the bloodstream were identified using UPLC-MS/MS. RNA-seq was conducted to identify differentially expressed genes and altered signaling pathways in colonic tissue. Furthermore, 16S rDNA sequencing and fecal microbiota transplantation were employed to determine whether KANF ameliorates UC by modulating the gut microbiota. RESULTS: KANF demonstrated significant therapeutic efficacy in alleviating UC in both clinical patients and animal models. Integrated analysis combining network pharmacology and RNA-seq validated that KANF attenuates intestinal inflammation by inhibiting NF-κB/NLRP3 activation. Furthermore, 16S rDNA sequencing revealed that KANF restores gut microbial homeostasis, and fecal microbiota transplantation experiments confirmed that the suppressive effect of KANF on NF-κB/NLRP3 signaling is primarily mediated through gut microbiota remodeling. CONCLUSION: KANF can significantly ameliorate symptoms in both clinical UC patients and DSS-induced colitis mice. KANF exerts its multi-target anti-colitic effects through regulation of the gut microbiota and subsequent suppression of the NF-κB/NLRP3 signaling cascade.