Long-term ginsenoside administration prevents memory impairment in aged C57BL/6J mice by up-regulating the synaptic plasticity-related proteins in hippocampus

Behav Brain Res. 2009 Aug 12;201(2):311-7. doi: 10.1016/j.bbr.2009.03.002. Epub 2009 Mar 17.


Memory impairment is considered to be one of the most prominent consequences of aging. Deterioration of memory begins in advance of old age in animals, including humans. Thus, it is extremely important to prevent memory decline for increasing healthy aging. Ginsenoside, the effective ingredient of ginseng, has been reported to have a neuron beneficial effect, but the preventive role on memory impairment and the underlying mechanisms have not been well determined. In the present study, C57BL/6J mice aged 12 months were chronically treated with ginsenoside 100mg/kg per day for 8 months. Placebo-treated aged mice, young and adult ones (4- and 8-month-old, respectively) were used as controls. The efficacious effect of ginsenoside was manifested in the amelioration of memory impairment in aged mice by Morris water maze and step-down tests. Compared with aged control group, the plasticity-related proteins including phospho-N-methyl-d-aspartate receptor1 (NMDAR1), phospho-calcium-calmodulin dependent kinase II (CaMK II), phospho-PKA catalytic beta subunit (PKA Cbeta), phospho-cAMP-response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) in hippocampus significantly increased in ginsenoside treated group. These findings suggest that ginsenoside is effective on the prevention of age-related memory impairment, and the up-regulation of plasticity-related proteins in hippocampus may be one of the mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Brain-Derived Neurotrophic Factor / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / drug effects
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / drug effects
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / metabolism
  • Female
  • Ginsenosides / administration & dosage*
  • Hippocampus / drug effects
  • Hippocampus / enzymology*
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Nootropic Agents / administration & dosage*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Time Factors


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Ginsenosides
  • NMDA receptor A1
  • Nerve Tissue Proteins
  • Nootropic Agents
  • Receptors, N-Methyl-D-Aspartate
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2