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. 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) 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 a ≧ normal C57BL / 6J mice were measured by 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; similar results. The densitometric measures of GSK-3β in APP mice increased significantly compared to the control group (P = 0.008). And the GSK-3β expression in donepezil and GEPT groups were all decreased, there was a 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 s uch effect ismore significant in 11-month-old mice. This partially explains the neuroprotecting mechanism of GEPT in preventing and treating of AD.