Ginsenoside Rg1 ameliorates the cognitive deficits in D-galactose and AlCl3-induced aging mice by restoring FGF2-Akt and BDNF-TrkB signaling axis to inhibit apoptosis

Int J Med Sci. 2020 Apr 15;17(8):1048-1055. doi: 10.7150/ijms.43979. eCollection 2020.

Abstract

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

Keywords: Morris water maze; estradiol; ginsenoside Rg1; learning and memory; step down avoidance test.

MeSH terms

  • Aging / drug effects
  • Aging / physiology
  • Aluminum Chloride / administration & dosage
  • Aluminum Chloride / toxicity
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Behavior Observation Techniques
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition / drug effects
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / metabolism
  • Galactose / administration & dosage
  • Galactose / toxicity
  • Ginsenosides / pharmacology*
  • Ginsenosides / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Panax / chemistry
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Ginsenosides
  • Membrane Glycoproteins
  • Fibroblast Growth Factor 2
  • Aluminum Chloride
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • ginsenoside Rg1
  • Galactose