Cinnamaldehyde and hesperetin attenuate TNBS-induced ulcerative colitis in rats through modulation of the JAk2/STAT3/SOCS3 pathway.

Ulcerative colitis is an autoimmune inflammatory disorder with a negative impact on the life quality of patients. Cinnamaldehyde and hesperetin were chosen due to their antioxidants and anti-inflammatory effects. This study explored the protective effects of cinnamaldehyde (40 and 90 mg/kg, po) and hesperetin (50 and 100 mg/kg, po) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis in rats. Cinnamaldehyde and hesperetin significantly improved macroscopic and histopathological examinations with a significant reduction in myeloperoxidase and intracellular adhesion molecule-1 expression. They significantly reduced colon oxidative stress by a significant elevation in both reduced glutathione content and superoxide dismutase activity with a significant reduction of NO content. Furthermore, cinnamaldehyde and hesperetin alleviated the inflammatory injury by a significant reduction in interleukin-6 along with suppression of nuclear factor-κB, receptor for advanced glycation end products, and tumor necrosis factor-α expression. Moreover, cinnamaldehyde and hesperetin significantly decreased p-JAK2 and p-STAT3 while significantly increased suppressors of cytokine signaling 3 (SOCS3) protein expression. In conclusion, cinnamaldehyde and hesperetin counteracted TNBS-induced ulcerative colitis through antioxidant, anti-inflammatory properties as well as modulation of the JAk2/STAT3/SOCS3 pathway.