Abstract: Objective: To investigate whether quercetin antagonizes oxidative pancreatic damage in diabetic rats through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Methods: Forty-eight specific pathogen-free (SPF) Sprague-Dawley (SD) rats were selected for this study. Ten animals were randomly assigned to the control group and the remaining 38 rats were used to establish a model of type 2 diabetes mellitus (T2DM) by feeding a high-fat diet and simultaneously injecting streptozotocin (STZ) at a dose of 30 mg/kg mb. Random blood glucose no lower than 16.7 mmol/L was used as a criterion to confirm successful model establishment in 30 rats. According to glucose levels, the rats with T2DM were randomly divided into three equal groups (n = 10): model, and low- and high-dose quercetin intervention. After continuous gavage for 12 weeks, the degree of oxidative damage and antioxidant indicators in pancreatic homogenate were evaluated. The protein and mRNA expression levels of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST) and NADP(H):quinone oxido-reductase 1 (NQO1) were measured by Western Blot and real-time fluorescence quantitative polymerase chain reaction. Results: Quercetin at both low and high doses could significantly reduce blood glucose levels and pancreatic malondialdehyde (MDA) content in T2DM rats (P < 0.05), alleviate insulin resistance, increase the activity of antioxidant enzymes such as SOD (P < 0.05), and up-regulate the protein and mRNA expression of Nrf2, HO-1 and NQO1 (P < 0.05). Conclusion: Quercetin may play a role in preventing and treating diabetes by activating the Nrf2 signaling pathway in pancreatic tissue and up-regulating the expression of downstream antioxidant enzymes to reduce oxidative damage, improve insulin resistance and regulate blood glucose levels.

Key words: diabetes; antioxidant capacity; hypoglycemic effect; Nrf2 signaling pathway