摘要
OBJECTIVE： To investigate the neuroprotective mechanism of combination extract of Renshen （Ponax Ginseng）, Yinyanghuo （Herba Epimedii Brevi-comus）, Yuanzhi （Radix Palygalae） and Jianghuang （Rhizoma Curcumae Longae） （GEPT） in treating AI- zheimer＇s disease on the target of glycogen syn- thase kinase 3β（GSK-3β）. METHODS： Three-month-old APPV7171 transgenic mice were randomly divided into ten groups （n=12 per group） and intragastrically administrated vehi- cle 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＋GI 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 APPV7171 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-313 expression of donepezil or OEPT group were all significantly de-creased （Donepezil vs APP： P=0.041; GI 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 in- creased significantly as compared with the control group （P=0.008）. And the GSK-3β expression indonepezil 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. CONCLUS
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 m
基金
Supported by Grant from the Innovative Research Team for Alzheimer's Disease's Prevention and Treatment of Ministry of Education of China (No. IRT-08-010)
the Project on Absorption of Intellects by Institutions of Higher Education for Academic Disciplinary Innovations (the "111 Project") (No.B08006)
the National Natural Science Foundation of China(No. 30973738)
the National Key Technology R & D Program(No. 2009BA177B09)
the Technological Platform of Clinical Evaluation and Research for New Herbal Medicinal Products(No. 2011ZX09302-006-01)
the Innovative Research Team in Beijing University of Chinese Medicine (No. 2011-CXTD-21)
Research Fund of Capital Medical Development (No.SF-2009-Ⅲ-11)
the Study of Secondary Prevention with Chinese Herbal Medicine for Chronic Diseases (No.Z111107056811043)
