Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.
Keywords: Akt signaling; Diabetic encephalopathy; Morin; brain; neuronal apoptosis; oxidative stress.