Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats

Diabetes-related cognitive dysfunction is a consequence of changes within the central nervous system that are secondary to chronic hyperglycemia, oxidative stress, and cholinergic dysfunction, and probably therefore anti-diabetics, anti-oxidants, and acetylcholine esterase (AChE) inhibitors were found to have beneficial effects in animal models. Quercetin, a bioflavonoid widely distributed in the plants is reported to be a potent anti-diabetic, anti-oxidant, AChE inhibitor, and memory enhancer. Therefore, we screened its influence against diabetes-induced cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water and elevated plus maze (EPM) paradigms. Thirty days after diabetes induction rats exhibited marked and persistent hyperglycemia, weight loss, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Treatment with quercetin (5-20 mg/kg, p.o., twice daily, 30 days) in streptozotocin-induced diabetic rats prevented the changes in blood glucose, body weight, and performance in Morris water and elevated plus maze tasks. In another set of experiment, quercetin (40 mg/kg, p.o., twice daily) treatment during training trials (31-35 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. This treatment also decreased blood glucose levels, but had no influence on body weights. These effects were comparable to vitamin C (100 mg/kg, twice daily, 30 days) and donepezil (3 mg/kg day 31-day 35, during training trials), and devoid of any motor deficit and anxiety-like effect when tested in open field test. In conclusion, quercetin may provide a new potential option for prevention of the cognitive dysfunction in diabetes.