Effect of Icariside Ⅱ on Learning and Memory Abilities of Mice with Alzheimer's Disease via regulating PI3K/Akt Signaling Pathway
Objective:To investigate the effect of icariside Ⅱ(ICS Ⅱ)on the learning and memory abilities of mice with Alzheimer's disease(AD)and its molecular mechanism.Methods:7-month-old APP/PS1 double-transgenic mice were randomly divided into the model group,ICS Ⅱ group,and positive control group,which were administered by gavage once a day for 30 days.Morris water maze and nesting experiment were used to test the learning,memory,and living abilities of mice;Aβ sedimentation and cell apoptosis in the brain of mice were detected using immunofluorescence histochemistry method.The correlation between the anti-apoptotic effect of ICS Ⅱ and the PI3K/Akt signaling pathway was studied using Western Blot.Results:Compared with the model group,the learning,memory,and living abilities of mice in the ICS Ⅱgroup were significantly improved(P<0.01);the fluorescence intensity of Aβ and number of positive cleaved caspase-3 cells in the hippocampus and cortex of mice in the ICS Ⅱ group were significantly reduced(P<0.05,P<0.01),indicating that ICS Ⅱ could inhibit Aβ sedimentation,reduce neuronal cell apoptosis,and thereby protect the brain tissue.At the same time,the protein expression of PI3K and ratio of p-Akt/Akt in the hippocampus of mice in the ICS Ⅱ group was significantly increased(P<0.05,P<0.01),while the ratio of Bax/Bcl-2 was significantly decreased(P<0.01),indicating that ICS Ⅱactivated the PI3K/Akt signaling pathway,inhibited expression of pro-apoptotic proteins,and increased the expression of anti-apoptotic proteins,thus exerting an anti-apoptotic effect.Conclusion:ICS Ⅱ has a significant neuroprotective effect on the brain of mice with AD;it improves the cognitive ability of the mice obviously,and the mechanism may be related to the activation of the PI3K/Akt signaling pathway.