Colitis is an intestinal disorder characterized by uncontrolled inflammation and epithelial barrier dysfunction, with limited effective pharmacological options available for veterinary clinical application. Our work evaluated the protective effects and mechanisms of Vaccarin (a flavonoid glycoside from Vaccaria segetalis) in a C57BL/6 murine model of dextran sulfate sodium (DSS)-induced colitis. The mice were randomized into 5 groups: Control, DSS, DSS+Vaccarin-L (1mg/kg), DSS+Vaccarin-H (4mg/kg), and DSS+mesalazine (100mg/kg, a reference drug used off-label in veterinary practice). Vaccarin improved clinical presentation, including reduced DAI, weight loss, and colon shortening. Besides, the results indicate that Vaccaria preserved epithelial structure, attenuated apoptosis, restored tight junction proteins, suppressed IL-1β and IL-18 production, and reversed autophagy impairment. Transcriptomics and protein validation identified FSTL3 as a novel target, with DSS-induced FSTL3 upregulation suppressed by Vaccarin in a dose-dependent manner. Autophagy inhibitor 3-MA abrogated Vaccarin’s protective effects, confirming the FSTL3-autophagy axis. In conclusion, Vaccarin ameliorates colitis by maintaining intestinal epithelial integrity, suppressing inflammation, and restoring autophagy flux via FSTL3 regulation, highlighting its potential as a veterinary therapeutic for colitis to alleviate gut-related morbidity and improve animal welfare.

To Cite This Article: Li Y, Kong H, Wang Y, Dong S, Pengfei Z, Li J, Yu H and Liang Y, 2025. Vaccarin ameliorates colitis by enhancing autophagy and suppressing inflammation mediated by FSTL3 in mice. Pak Vet J, 45(4): 1964-1971. http://dx.doi.org/10.29261/pakvetj/2025.xxx