((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Aβ1-42-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis.

Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3β (GSK-3β) inhibitor, on the learning and memory function of rats with amyloid-β1-42 (Aβ1-42)-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Aβ, donepezil, and low-dose and high-dose 9b groups. The rats in the Aβ, donepezil, and two 9b intervention groups received a single microinjection of 10 μg of Aβ1-42 into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Aβ1-42, phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Aβ group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Aβ1-42. The novel GSK-3β inhibitor 9b could improve learning and memory dysfunction caused by Aβ1-42 through its antioxidant and antiapoptotic effects.