Geniposidic acid attenuates DSS‐induced colitis through inhibiting inflammation and regulating gut microbiota

Abstract Geniposidic acid (GPA) is a bioactive compound isolated from Gardenia jasminoides Ellis ( Rubiaceae ) that has long been used to treat arthritis, jaundice, and hypertension. However, the therapeutic effects of GPA against colitis remain underexplored. This study aimed to investigate the effect of GPA on the remission of colitis and the underlying mechanisms. A DSS‐induced colitis mouse model was used to evaluate the influence of GPA on the modulation of gut microbiota and intestinal epithelial barrier function. Our results indicated that GPA improved DSS‐induced mouse colitis, including loss of body weight, disease activity index (DAI), colon length, and colonic pathological damage. DSS‐induced destruction of the intestinal barrier was also significantly repaired by GPA treatment. In addition, the relative levels of pro‐inflammatory cytokines, such as IL‐1β and TNF‐α, were markedly alleviated by GPA. Furthermore, western blot analysis revealed that GPA downregulated the protein expression of the nuclear transcription factor NF‐κB. Finally, we first demonstrated that GPA could alleviate gut microbiota dysbiosis in mice with colitis by bacterial 16S rRNA sequencing. In conclusion, our study demonstrates the therapeutic and protective effects of GPA on IBD and provides novel insights into the prevention of colitis by targeting gut microbiota metabolism using natural products.