Effect of Donepezil on Vascular Dementia in Rats via PI3K/AKT Pathway

Abstract

Background: Previous studies have shown that Donepezil has therapeutic effects on vascular dementia (VD). PI3K/AKT involves in oxidative stress injury and cell apoptosis. This study investigated whether Donepezil affects the neurological function and apoptosis of VD mice via PI3K/AKT signaling. Methods: Mice were assigned into Sham group, VD group, VD+Donepezil groupfollowed by analysis of mice learning and memory ability by Water maze test, p-AKT expression by Western blot, Caspase-3 activity, MDA content, SOD activity and GSH-Px in hippocampus. HT22 cells were cultured and separated into control group, I-R group and I-R+Donepezil group followed by measuring p-AKT level, ROS content and apoptosis. Results: Learning and memory abilities of VD group mice were significantly decreased, Caspase-3 activity and MDA in brain tissue were significantly increased, along with decreased SOD activity, GSH-Px and p-AKT level. Donepezil treatment can significantly improve VD mice learning and memory ability, reduce Caspase-3 activity and MDA in brain tissue, increase SOD activity, GSH-Px and p-AKT level. In vitro, I-R treatment significantly induced apoptosis of HT22 cells, increased ROS production and decreased p-AKT level. Donepezil treatment could up-regulate p-AKT in HT22 cells and reduce apoptosis and ROS production in HT22 cells. Conclusion: Donepezil improves the function of brain nerve in VD mice through regulating PI3K/AKT pathway, thus reducing oxidative stress injury and apoptosis of brain nerve cells.