Matrine protects against DSS-induced murine colitis by improving gut barrier integrity, inhibiting the PPAR-α signaling pathway, and modulating gut microbiota

Matrine is a naturally occurring quinolizidine alkaloid with various bioactivities. However, little is known of its function on ulcerative colitis (UC). Here, we investigated the effect and underlying mechanisms of matrine on dextran sulfate sodium (DSS)-induced UC mice. In this study, different concentrations of matrine were given to mice with DSS-induced colitis for a week. The symptoms of colitis, colonic pathology, inflammation-related indicators, and intestinal mucosal barrier function were detected and analyzed. Moreover, RNA-seq analysis in colon tissues was conducted, and 16S rDNA sequencing was carried out to evaluate the gut microbiota of colon contents. The results showed that matrine significantly alleviated clinical activity and histological changes of UC mice, inhibited the production of the pro-inflammatory cytokines, and improved gut barrier integrity. Moreover, RNA-seq analysis and experimental verification showed that matrine significantly inhibited the peroxisome proliferator-activated receptor-α (PPAR-α) signaling pathway. 16S rDNA sequencing revealed that matrine altered the composition and functions of gut microbiota, increased the abundance of Barnesiella intestinihominis and decreased the abundance of Helicobacter ganmani at the species level. In conclusion, matrine ameliorated DSS-induced colitis by improving gut barrier integrity, inhibiting the PPAR-α signaling pathway, and modulating gut microbiota. These suggested that matrine may be a therapeutic agent for UC treatment.