Effect Of Icaritin On Improving Learning And Memory Ability Of APP/PS1 Transgenic Mice Through AMPK Signal Pathway

Objective:To confirm that icaritin（ICT）has an anti-Alzheimer disease（AD）effect in APP/PS1transgenic mouse and to analyze whether its mechanism is related to the regulation of AMP-activated protein kinase（AMPK）signal pathway,to lay a foundation for further development of ICT as a therapeutic drug for AD.Methods:APP/PS1 transgenic mice and wild type C57BL/6 control mice were divided into 4 groups:WT+Vehicle,WT+ICT,APP/PS1+Vehicle,APP/PS1+ICT,APP/PS1+ICT and WT+ICT were given ICT 40 mg/kg,APP/PS1+Vehicle and WT+Vehicle by intragastric administration of the same volume of solvent,once a day.After 3 months of continuous administration,the learning and memory abilities of mice were tested by Y maze and Morris water maze.After that,brain tissues were collected and Thioflavin S staining was used to detect amyloid plaques.Enzyme-linked immunosorbent assay（Elisa）was used to detect Aβ_1-42 and Aβ_1-40.Immunofluorescence was used to detect the expression ofβ-site APP cleaving enzyme 1（BACE1）.amyloid precursor protein（APP）,AMP-activated protein kinase phosphorylation（p-AMPK）,and peroxisome proliferator-activated receptorγcoactivator 1α（PGC1-α）were detected by Western blot,virtual molecular docking was used to explore the binding ability of ICT to protein,and proteome quantitative technique was used to detect the proteome effect of ICT on APP/PS1transgenic mice.Results:In the Morris water maze test,compared with the APP/PS1 mouse model group,ICT reduced the escape latency and increased the percentage of stay time in the target quadrant of APP/PS1 mice;in the Y maze test,ICT increased the spontaneous alternation rate of APP/PS1mice;compared with the APP/PS1 mouse model group,ICT did not reduce the area of amyloid plaques in the cortex and hippocampus of APP/PS1 mice.ICT did not affect the expression of APP in the brain of APP/PS1 mice.After the administration of ICT,the contents of p-AMPK and PGC1-αincreased,the expression of BACE1 decreased and the content of Aβdecreased in the brain of APP/PS1 mice,and the binding energy of ICT to AMPK virtual molecule was-4.5 kcal/mol,after the administration of ICT,cab39 showed an upward trend,and the binding energy of ICT and cab39 virtual molecules was-7.1kcal/mol.Conclusion:ICT improves the cognitive function of APP/PS1 transgenic mice,and its mechanism may be related to the regulation of the AMPK signal pathway and inhibition of A β production.