Effect and mechanism of Donepezil hydrochloride on Alzheimer’s disease

Abstract

Objective: To explore the effect and mechanism of donepezil hydrochloride on Alzheimer’s disease (AD).Methods: Thirty-six 3-month-old SD rats were selected as the research subjects and randomly divided into a normal control (NC) group and a model group. The model group was given continuous intraperitoneal injection of D-galactose solution (120 mg/kg/d) combined with aluminum trichloride (10 mg/kg/d) by gavage for 60 days. Morris water maze test was conducted to test the learning and memory abilities of the rats, and AD rats were selected. After modeling, AD rats were divided into a normal saline (NS) group and a drug treatment (DT) group. The DT group was given donepezil hydrochloride (1.0 mg/kg) by gavage intervention, and the NC group and the NS group were given equal volumes of physiological saline by gavage. After 4 weeks of intervention, Morris water maze test was conducted to detect the escape latency, the number of platform crossings and residence time in the target quadrant, the rats were euthanized, with serum and hippocampal tissues collected, and hippocampal tissue homogenate (10%) was prepared by using NS. Enzyme linked immunosorbent assay (ELISA) was used to detect the inflammatory and oxidative stress indicators in rat hippocampal tissues and serum, and hematoxylin eosin (HE) staining was used to observe pathological damage in rat hippocampal tissues.Results: Compared with the NC group, the NS group showed a significant increase in escape latency (p < .05), a significant decrease in the number of platform crossings and residence time in the target quadrant (p < .05), and a significant decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum and hippocampal tissues (p < .05). The content of malondialdehyde (MDA) was significantly increased (p < .05), and the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased (p < .05). Compared with the NS group, the DT group can significantly reduce the escape latency (p < .05), increase the number of platform crossings and residence time in the target quadrant (p < .05), significantly increase the activities of SOD and GSH-Px in serum and hippocampal tissues and reduce the content of MDA (p < .05) and the levels of IL-6 and TNF-α (p < .05). After intervention with donepezil hydrochloride, the number of neurons in the hippocampus were significantly increased.Conclusions: Donepezil hydrochloride can improve the learning and memory abilities of rats, reduce the levels of oxidative stress and inflammation in the brain and serum, and improve pathological damage in the hippocampus.