title: A combination extract of Renshen (Panax Ginseng), Yinyanghuo (Herba Epimedii Brevicornus), Yuanzhi (Radix Palygalae) and Jianghuang (Rhizoma Curcumae Longae) decreases glycogen synthase kinase 3beta expression in brain cortex of APPV7171 transgenic mice.
abstract: 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 3beta (GSK-3beta).
  
  
  METHODS
  Three-month-old APPV7171 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) x day(-1)), and GEPT groups were given small dose of GEPT (APP+Gs group) (0.075 g/ kg(-1) x 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) x 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-3beta 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-3beta in the cerebral cortex of 7-month-old APP group (compare to control group P = 0.003), while the GSK-3beta expression of donepezil or GEPT group were all significantly decreased (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-3beta in APP mice increased significantly as compared with the control group (P = 0.008). And the GSK-3beta 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-3beta in the GEPT group.
  
  
  CONCLUSIONS
  GEPT can effectively decrease the level of GSK-3beta expression in the brain cortex of APPV7171 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.
authors.affiliation: Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Tian
authors.forename: Xuekai
authors.initials: X
authors.lastname: Zhang
authors.forename: Chuiyou
authors.initials: C
authors.lastname: Zeng
authors.forename: Mingqing
authors.initials: M
authors.lastname: Wei
authors.forename: Pengwen
authors.initials: P
authors.lastname: Wang
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D030024:Curcuma / Q000737:chemistry*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D005894:Panax / Q000737:chemistry*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3