Abstract: The objective of the present study was to evaluate the modulating effects of gastrodin on cognitive deficits.Rats were administered bilaterally in hippocampal CA1 area by injecting Aβ1-42 to produce an animal model of Alzheimer’s Disease (AD).The rats were randomly subdivided into 5 groups:Control group,Model group,Gastrodin-L (1 mg/kg),Gastrodin-M (5 mg/kg) and Gastrodin-H (25 mg/kg).The Morris water maze and passive avoidance tests were used to determine the neuroprotective effects of gastrodin on Aβ1-42-induced learning and memory impairments.The levels of superoxide dismutase (SOD),malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were analyzed to determine the oxidative stress status by ELISA.Brain ultrastructure was observed via optical microscopy (HE staining).The apoptosis of neurons was detected by TUNEL staining,The proteins levels of total glycogen synthase kinase-3β (GSK-3β) and phospho-GSK-3β (p-GSK-3β) were measured by Western blot.The results showed that the memory function was significantly reduced in model group of rats,and severe brain injury and neuronal apoptosis were also observed in the model group.Compare with control group,the activities of total SOD and GSH-Px were markedly decreased,but the levels of MDA were significantly increased in the model group.Gastrodin (5 mg/kg and 25 mg/kg) improved previous learning and memory impairments than the model groups.Compared with the model group,the activities of total SOD and GSH-Px were markedly enhanced,but the levels of MDA was significantly reduced in Gastrodin-M and Gastrodin-H groups.Meanwhile,Gastrodin (5 mg/kg and 25 mg/kg) also significantly attenuated Aβ1-42-induced brain injury and neuronal apoptosis.In addition,the expression levels of p-GSK-3β expression was upregulated in the Gastrodin-H group.Taken together,our findings suggest that Gastrodin have beneficial effects on the cognitive impairments seen in an Aβ1-42-induced model of Alzheimer's disease via inhibiting oxidative stress and anti-apoptotic responses.

Key words: Gastrodin;Alzheimer disease, Aβ1-42, antioxidant, anti-apoptotic, GSK-3β