Metformin and ascorbic acid combination therapy ameliorates type 2 diabetes mellitus and comorbid depression in rats

Abstract Diabetes mellitus and depression are the common comorbid disorders affecting humans worldwide. There is an unmet need to develop therapeutic strategies to treat both diabetes mellitus and comorbid depression. The present study evaluated the effectiveness of metformin and ascorbic acid against type 2 diabetes mellitus and comorbid depression in rats. Four groups of diabetic rats were orally administered with vehicle (1 mL/kg), metformin (25 mg/kg), ascorbic acid (25 mg/kg), or combination of metformin (25 mg/kg) and ascorbic acid (25 mg/kg) for 11 consecutive days. Diabetes was induced by single-dose administration of streptozotocin (65 mg/kg, i.p.) with nicotinamide (120 mg/kg, i.p.). Comorbid depression was induced by five inescapable foot-shocks (2 mA, 2 ms duration) at 10 s intervals on days 1, 5, 7, and 10. One group of healthy rats received only vehicles to serve as nondiabetic control group. On day 11, animals were sacrificed, and blood and brain samples were collected from each rat following forced swim test. Plasma glucose, insulin, and corticosterone levels were estimated in plasma. The levels of monoamines, proinflammatory cytokines, and oxidative stress were measured in prefrontal cortex. The combination therapy significantly reduced immobility period, glucose, and corticosterone levels relative to diabetes with comorbid depression group. Furthermore, the combination therapy increased the levels of insulin and monoamines, and caused a significant reductions in oxidative stress and proinflammatory cytokines. In conclusion, the present study revealed that metformin and ascorbic acid combination therapy could be a potential strategy to treat type 2 diabetes mellitus and comorbid depression.