The Effects And Its Mechanisms Of Quercetin On Memory Impairment In Mice And Vascular Dementia In Rat

Memory impairment is common symptoms of a variety of cerebropathy, for example Alzheimer, Vascular Dementia, and has become a frequent-occurring disease. So the research of memory impairment has contributed to the treatment of multiple cerebropathy.Vascular dementia (VD) is dementia syndrome which is characterized by cognitive dysfunction, is caused by a variety of cerebral vascular diseases and is one of the most common types of senile dementia. With the increase in vascular disease and socio-demographic aging, the incidence of VD continuously ascends. In Asia, the rate of occurrence is fairly high because of the high rate occurrence of stroke. In China, VD accounts for 60-70% dementia and the incidence of VD is the top of senile dementia. So to explore the prevention and treatment of VD will make good sense.Quercetin has a wide range of biological activity, such as anti-oxidation and removal of the oxygen-derived free radicals, anti-fibrosis, anti-tumor and so on. Some reports showed that Quercetin had the protective effect on the learning and memory disorders induced by Colchicine or D-galactose in mice. But the effects of Quercetin on memory dysfunction and vascular dementia reported less.In order to further study the effects of Quercetin on memory dysfunction and vascular dementia, in this experiment, the protective effect and its mechanisms of Quercetin on the learning and memory disturbance in mice induced by chemicals and vascular dementia rats were observed. This will provide a theoretical basis for Quercetin to treat VD patients.Methods:1. Memory impairments of acquisition, retention and retrieval were induced respectively by scopolamine, sodium nitrite and the 40% ethanol. The step-down test and the Morris water maze performance were used to evaluate the effects of Quercetin (200,100,50 mg/kg, ig,10 d) on the ability of learning and memory in mice. The activities of AchE and SOD and the content of MDA in the brain tissues were determined.2. The vascular dementia rat model was established by two-vessel occlusion, combined with intraperitoneal injection of Sodium Nitroprusside (2.5 mg/kg). Behaviors were detected by morris water maze; observed therapeutic effects and mechanisms of Quercetin (140,70,35 mg/kg, ig,15 d) on VD rats by detecting NOS, LDH, ATP activities and NO, LD content in the brain tissue, ET-1, CGRP content in the serum and hemorrheological changes.Result:1. In water maze, mice with memory impairment induced by Scopolamine hydrobromide prolonged the escape latency to find platform, reduced the times to cross the platform (P<0.01) while Quercetin can shorten the escape latency to reach platform, increase the times to cross the platform (P<0.01 or P<0.05). In step-down test, Quercetin extended the escape latency of jumping off the platform firstly, reduced the number errors of jumping off the platform within 5 min of the model groups of mice’s retention and retrieval disorder (P<0.01 or P<0.05).2. Quercetin can increase AchE activity of mice with memory acquisition disturbance, enhance SOD activity and reduce MDA content of mice with memory consolidation disturbance (P<0.01 or P<0.05).3. On VD model in rats, Quercetin can shorten the escape latency to reach platform, increase the times to cross the platform (P<0.01 or P<0.05).4. On VD model in rats, Quercetin can enhance LDH, ATP activity in the brain tissue and elevate CGRP content in the serum (P<0.01 or P<0.05).5. On VD model in rats, Quercetin decreased NO、LD content and inhibited NOS activity in the brain tissue, reduced the release of ET-1 in the serum (P<0.01 or P<0.05).6. On VD model in rats, Quercetin could reduce the values of high, medium and lower shear rates, plasma viscosity, hematocrit and fibrinogen content(P<0.01 or P<0.05).Conclusion:1. Quercetin could ameliorate the learning and memory disturbance of mice induced by chemicals and this improvement effects might have relation with improving cholinergic system and antioxidation.2. Quercetin could improve cognition disorder of vascular dementia rats and might closely connect with decreasing cerebral NOS activity and NO content, promoting brain energy metabolism, balancing ET-1 and CGRP level and improving hemorheology.