OBJECTIVE:To investigate the neuroprotective mechanism of combination extract of Renshen(Panax Ginseng),Yinyanghuo(Herba Epimedii Brevicornus),Yuanzhi(Radix Palygalae) and Jianghuang(Rhizoma Curcumae Longae)(GEPT) in treating Alzheimer's disease on the target of glycogen synthase kinase 3β(GSK-3β).METHODS:Three-month-old APPV717I transgenic mice were randomly divided into ten groups(n=12 per group) and intragastrically administrated vehicle or medicines:APP group was given 0.5% CMC,donepezil group was given donepezil(APP + D group)(0.92 mg/kg-1·day-1),and GEPT groups were given small dose of GEPT(APP+Gs group)(0.075 g/kg-1·day-1),medium dose(APP+Gm group)(0.15 g/kg-1·day-1),and large dose(APP+Gl group)(0.30 g/kg-1·day-1) for 4 or 8 months,respectively.Three-month-old C57BL/6J mice as vehicle controls(n=12) were given 0.5% CMC for 4 or 8 months as well.The GSK-3β expression in the cortex of 7-and 11-month-old APPV717I transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry.RESULTS:Immunohistochemistry analysis showed significant increase of GSK-3β in the cerebral cortex of 7-month-old APP group(compare to control group P=0.003),while the GSK-3β expression of donepezil or GEPT group were all significantly decreased(Donepezil vs APP:P=0.041;Gl vs APP:P= 0.049;Gm vs APP:P=0.029;Gh vs APP:P=0.036).Western blot analysis showed similar results.The densitometric measures of GSK-3β in APP mice increased significantly as compared with the control group(P=0.008).And the GSK-3β expression in donepezil and GEPT groups were all decreased.There was significant difference between Gh group or donepezil group and the control group(P=0.05).Similar findings were shown in the 11-month-old mice in each group,except for greater decrease of GSK-3β in the GEPT group.CONCLUSION:GEPT can effectively decrease the level of GSK-3β expression in the brain cortex of APPV717I transgenic mice,and such effect is more significant in 11-month-old mice.This partially explains the neuroprotecting mechanism of GEPT in preventing and treating of AD.