Imrecoxib alleviates hepatic damage in type 2 diabetic rats by modulating PI3K/AKT/NF-κB signaling

Objective: To investigate the influence and underlying mechanisms of imrecoxib on liver damage in rats with type 2 diabetes mellitus (T2DM). Methods: A rat model of T2DM was established by a high-fat diet and streptozotocin administration. Rats were then treated with imrecoxib 10, 20, or 40 mg/kg for 5 weeks. Body weight and fasting blood glucose levels were measured. The analysis included serum liver function, blood lipid profiles, and the levels of inflammatory factors in the rats. Liver tissue histology was evaluated using hematoxylin and eosin staining. Western blotting was conducted to measure the liver expression of proteins such as AKT, PI3K, NF-κB, p-AKT, p-PI3K, and p-NF-κB. Results: Rats treated with imrecoxib showed a greater weight gain compared to untreated diabetic rats. Compared to untreated diabetic rats, imrecoxib at all three doses reduced alanine aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, and significantly increased the levels of IL-10 and IL-4. In imrecoxib-treated rats, the expression levels of AKT, PI3K, p-AKT, and p-PI3K were higher in comparison to the diabetes group, whereas the expression of p-NF-κB was lower. Conclusions: Imrecoxib could alleviate hepatic damage in T2DM rats by modulating PI3K/AKT/NF-κB signaling.