Abstract

Introduction Ulcerative colitis (UC) is one of the predominant forms of inflammatory bowel disease (IBD), and it is a chronic and recurring inflammation of the gastrointestinal trac. However, the therapies are associated with drug resistance and low responsiveness. Ferulic acid (FA) alleviates clinical signs and inflammatory mediators in UC, while the molecular mechanisms of FA regulation on UC remain elusive. The aim of this experiment is to ascertain the preventive mechanism of FA on the non-infectious UC. Methods Sixty male Kunming mice (6–8 weeks) were randomly allocated into six groups: Control (CON), Dextran sulfate sodium (DSS), FA+DSS, FA, Prednisone (Pdn), and Pdn+DSS group. Colonic histopathology, Interleukin-1β (IL-1β), interleukin-6 (IL-6), IL-10, IL-2 concentrations, fecal calprotectin (FC), fecal lactoferrin (FL), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, MDA content and total antioxidant capacity (T-AOC) were quantified by HE staining, transmission electron microscopy, and ELISA Kit. Gut microbiota composition was analyzed by sequencing of the 16S rRNA V4 gene region. Results Compared with the DSS group, FA administration significantly reduced IL-1β and IL-6 levels, FC and FL, promoted the increase of IL-2 and IL-10, markedly elevated activities of SOD, GSH-Px, CAT and total antioxidant capacity (T-AOC) activity, and decreased MDA levels. Moreover, preventive FA supplementation improved extensive inflammation infiltration and crypt destruction in colon of UC mice, mitochondrial damage in the colonic epithelial cells. Preventive FA supplementation exhibited a return to original levels of Muribaculaceae and Clostridia. Conclusion Collectively, FA and Pdn effectively attenuated DSS-induced UC by restoring colonic morphology, suppressing inflammatory mediators, enhancing antioxidant capacity, and regulating