Caffeic acid attenuates stress-induced colon inflammation and barrier disruption in Sprague-Dawley rats

Chronic stress promotes colonic inflammation by sustaining activation of the hypothalamic-pituitary-adrenal (HPA) axis, inducing oxidative stress, and disrupting barrier integrity, thereby exacerbating inflammatory bowel disease and irritable bowel syndrome. Therefore, there is a need for therapeutic compounds that can ameliorate stress-induced colonic inflammation. Caffeic acid (CA), a naturally occurring polyphenol found in coffee and tea, has shown potential anti-inflammatory and antioxidant properties. This study evaluated the effect of CA in a chronic unpredictable stress (CUS)-induced colon inflammation in rats. Animals were exposed to CUS for 14 weeks, with CA (50 mg/kg, p.o.) administered during the final 4 weeks as an intervention. CUS exposure induced depression-like behaviors, elevated stress hormone levels, and redox imbalance, as evidenced by increased malondialdehyde (MDA), nitrite, and reactive oxygen species (ROS), along with decreased reduced glutathione (GSH) and superoxide dismutase (SOD). Histological analysis revealed significant colonic damage, including crypt shortening, mucosal thickening, goblet cell loss, and mast cell infiltration. These changes were accompanied by reduced expression of tight junction proteins (ZO-1, claudin-1, and occludin) and increased expression of inflammatory mediators (PAR-2, IL-6, IL-1β, and NF-κB). CA treatment ameliorated behavioural alterations, restored redox balance and antioxidant defenses, and preserved mucosal architecture and goblet cell integrity. Mechanistically, CA suppressed PAR-2-mediated NF-κB signalling, thereby restoring intestinal barrier integrity. Collectively, these findings indicate that CA has therapeutic potential to attenuate stress-induced colonic inflammation by modulating stress-associated gastrointestinal disorders.