Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation

Aim This study aims to model ulcerative colitis in rats using acetic acid and monitor colitis development with the "Disease Activity Index (DAI)." Additionally, the clinical, biochemical, and histopathological effects of thymoquinone (TQ) and caffeic acid phenethyl ester (CAPE) on this model are examined. Materials and Methods The study used 40 male Wistar Albino rats, weighing between 190–303 grams. The rats were divided into five groups of 8 each: Group 1 (Control) received intraperitoneal 0.9% saline solution for 5 days; Group 2 (Colitis) received acetic acid to induce colitis and 10% ethanol solution intraperitoneally for 5 days; Group 3 (TQ) received acetic acid to induce colitis and intraperitoneal thymoquinone (10 mg/kg/day) for 5 days; Group 4 (CAPE) received acetic acid to induce colitis and intraperitoneal caffeic acid (10 micromol/kg/day) for 5 days; Group 5 (TQ + CAPE) received acetic acid to induce colitis and intraperitoneal thymoquinone and caffeic acid for 5 days. On the 5th day, rats underwent laparotomy under anesthesia, colectomy was performed, and colon samples were taken for biochemical and histological analysis. Serum samples were also collected for biochemical analysis. Results Significant differences were observed in the Disease Activity Index, TNF-α, catalase, glutathione peroxidase, IL-10, and MDA, indicating a balance between oxidant and antioxidant parameters. CAPE was found to have a higher anti-inflammatory effect than TQ histopathologically. The combined application of CAPE and TQ showed a synergistic effect, reducing oxidative stress markers and enhancing antioxidant levels. Conclusion The hypothesis of this study is that CAPE and TQ will effectively reduce inflammation in an experimental colitis model induced by acetic acid. The results largely support this hypothesis, showing that CAPE has a higher anti-inflammatory efficacy than TQ and that their combined use is more effective in reducing inflammation. These findings suggest that CAPE and TQ could be a potential combination for colitis treatment and should be considered for clinical applications. This study provides new insights into the use of anti-inflammatory agents in experimental colitis models and highlights the potential advantages of combining CAPE and TQ in clinical settings.