Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress

Abstract

Due to anti-diabetic and antioxidant activity of green tea epigallocatechin gallate (EGCG) and the existence of evidence for its beneficial effect on cognition and memory, this research study was conducted to evaluate, for the first time, the efficacy of chronic EGCG on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and -diabetic groups. EGCG was administered at a dose of 20 and 40 mg/kg/day for 7 weeks. Learning and memory was evaluated using Y maze, passive avoidance, and radial 8-arm maze (RAM) tests. Oxidative stress markers and involvement of nitric oxide system were also evaluated. Alternation score of the diabetic rats in Y maze was lower than that of control and a significant impairment was observed in retention and recall in passive avoidance test ( p < 0.01) and EGCG treatment (40 mg/kg) of diabetic rats significantly improved these parameters ( p < 0.05). Also, diabetic animals exhibited fewer correct choices ( p < 0.01) and more errors ( p < 0.005) in the RAM task and EGCG (40 mg/kg) significantly ameliorated these changes ( p < 0.05). Further, pretreatment with l-arginine as a substrate for nitric oxide synthase (NOS) and/or 7-nitroindazole as a neuronal NOS inhibitor attenuated and potentiated the beneficial effect of EGCG regarding learning and memory respectively. Meanwhile, increased levels of malondialdehyde (MDA) and nitrite in diabetic rats significantly reduced due to EGCG treatment ( p < 0.05). In summary, chronic green tea EGCG dose-dependently could ameliorate learning and memory deficits in STZ-diabetic rats through attenuation of oxidative stress and modulation of NO.