Curcumin, Thymoquinone, and Metformin: Impact on Serum Levels of AGEs, SDF-1, miR-192 and miR-497, and Hepatic Oxidative Stress and G6PD Expression in Diabetic Rats

Background: In a rat model of diabetes, this study investigated the impacts of curcumin (CUR), thymoquinone (TQ), and metformin (Met) on glycemic control, lipid profile, liver and kidney functions, serum advanced glycation end products (AGEs), stromal cell-derived factor-1 (SDF-1), miR-192 and miR-497 levels. Also, it evaluated their effects on hepatic oxidative stress markers [glutathione peroxidase-1 (GPx-1), superoxide dismutase (SOD), and malondialdehyde (MDA)] and hepatic G6PD expression. Methods: Fifty adult male Wistar rats (200-250g) were used. Diabetes was induced in 40 rats with a single dose of intraperitoneal streptozotocin (65 mg/kg), while 10 received citrate buffer (G1; control). The diabetic rats were divided into: G2 (untreated; positive control), G3 (CUR 100mg/kg/day), G4 (TQ 50mg/kg/day), and G5 (Met 50mg/kg/day). After 28 days, rats fasted for 12h before being euthanized. Glycemic indices, lipid profile, and liver and kidney function tests were performed. Serum AGEs, SDF-1, and miRNAs levels were measured using fluorescence assay, ELISA, and qPCR, respectively. Hepatic GPx-1 and SOD activity, MDA levels, and G6PD expression were assessed by ELISA, TBARS assay, and Western blotting, respectively) Results: All treatments improved glycemic control, lipid profile, and liver and kidney functions. They significantly reduced serum AGEs, SDF-1, and miR-192 levels, while restoring miR-497 levels. Additionally, they significantly increased hepatic GPX-1 and SOD activity, while decreased MDA levels, and G6PD expression. Notably, CUR demonstrated the most pronounced effect. Conclusion: CUR, TQ, and Met all demonstrated potential as adjunctive diabetes therapies by modulating metabolic and oxidative stress parameters, alongside gene expression.