Abbas_2026_Arch.Physiol.Biochem__1

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder that requires effective treatment strategies with minimal side effects. METHODS: DM was induced by intraperitoneal injection of nicotinamide (NA) at dose 60 mg/kg 15 minutes before streptozotocin (STZ) intraperitoneal injection (60 mg/kg) to 16 hours-fasted Wistar rats. The diabetic rats were treated with xanthine-based dipeptidyl peptidase-4 inhibitor (linagliptin) (1 mg/kg), and diosmin (10 mg/kg) either singly or in combination every other day for 4 weeks via oral gavage in NA/STZ-induced diabetic rats. RESULTS: Both linagliptin and diosmin potentially lowered the fasting and postprandial blood glucose levels, and fructosamine concentrations, indicating improved glycemic control. The combined treatment effects were the most potent. The treatments also improved serum lipid profile, and cardiac function markers, including AST and CK-MB, suggesting protective effects on the heart. Histopathological analysis demonstrated enhanced adipose tissue integrity and structural improvements. Additionally, inflammatory markers, including TNF-alpha and IL-1beta, were significantly reduced, highlighting the anti-inflammatory properties of linagliptin and diosmin. CONCLUSION: the findings suggest that linagliptin and diosmin exert strong anti-hyperglycemic, anti-hyperlipidemic, cardioprotective, and anti-inflammatory effects in diabetic rats; the combined treatment effect was the most potent.