Inflammatory bowel disease is an inflammatory disorder associated with systemic immune activation, contributing to neuroinflammation, behavioral impairments and disruption of the gut-brain axis. The present study investigated the effects of p-Coumaric acid derivatives: Artepillin C (ART-C), Baccharin (BAC), and Drupanin (DRU) on colonic damage, behavioral alterations, and oxidative stress in a dextran sulfate sodium (DSS)-induced colitis by administration of 3% DSS. Mice were treated with p-Coumaric acid derivatives (0.3, 1, or 3 mg/kg, p.o.), and disease activity index and colon length were evaluated as clinical parameters. Behavioral assessments included the open field test, novel object recognition test, elevated plus maze, and tail suspension test. Oxidative stress and inflammatory markers were quantified in colon, serum, cortex, and hippocampus, alongside histological analysis of colonic tissue. DSS administration induced clinical and histopathological alterations, increased oxidative stress, and impaired recognition memory, as well as anxiety- and depressive-like behaviors. p-Coumaric acid derivatives attenuated colonic damage, preserved tissue architecture, improved recognition memory, and reduced anxiety- and depressive-like behaviors, particularly at higher doses. These effects were associated with modulation of antioxidant defenses and reduction of lipid peroxidation and inflammatory markers. p-Coumaric acid derivatives exert protective effects in DSS-induced colitis, highlighting their potential as therapeutic agents for intestinal and neurobehavioral alterations associated with IBD.
