Evaluation of Anti-Inflammatory and Antioxidant Effects of Ferulic Acid and Quinic Acid on Acetic Acid-Induced Ulcerative Colitis in Rats

Abstract

Ulcerative colitis is a chronic inflammatory disease characterized by oxidative stress and the production of pro-inflammatory cytokines. Ferulic acid and quinic acid, two phenolic compounds, are thought to have potent antioxidant and anti-inflammatory properties. This study aimed to investigate the anti-inflammatory and antioxidant effects of ferulic acid and quinic acid in rats with acetic acid (AA)-induced ulcerative colitis. To this end, 64 Wistar rats were randomly divided into eight groups, each consisting of eight rats. AA was administered intrarectally to induce ulcerative colitis. Ferulic acid (20, 40, and 60 mg/kg), quinic acid (10, 30, 60, and 100 mg/kg), and dexamethasone (2 mg/kg) were received daily for five consecutive days. Then, the macroscopic and histopathological changes in the colon tissue were examined. Finally, the tissue levels of heme oxygenase 1 (HO1), nuclear factor erythroid 2-related factor 2 (NRF2), and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA expression and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were measured using the quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) methods, respectively. AA-induced ulcerative colitis in rats was associated with edema and severe damage to the epithelium, infiltration of inflammatory cells, and the presence of ulcers in the colon tissue. The results showed that rats who were administered AA showed a decrease in the expression of HO-1, Nrf2, and NQO1 and increased protein levels of TNF-α and IL-1β than the control group. Rats were administered ferulic acid, quinic acid and, dexamethasone significantly improved histopathological indices. The expression of HO-1, Nrf2, and NQO1 were upregulated by 60 mg/kg of ferulic acid, 60 and100 mg/kg of quinic acid and, 2 mg/kg of dexamethasone treatment compared to the ulcerative colitis group. The protein levels of TNF-α and IL-1β dose-dependently decreased by ferulic acid and quinic acid treatment compared to the ulcerative colitis group. Ferulic acid and quinic acid effectively reduce inflammation and mucosal damage in rats with ulcerative colitis, especially when administered in high doses. The possible mechanism of anti-inflammatory response by ferulic acid and quinic acid may involve the activating of the Nrf2/HO-1 pathway.

Keywords: Nrf2/HO‐1 pathway; ferulic acid; pro‐inflammatory cytokines; quinic acid; ulcerative colitis.