Neuroprotective effects of ginsenoside Rg1 through the Wnt/β-catenin signaling pathway in both in vivo and in vitro models of Parkinson's disease

Neuropharmacology. 2016 Feb:101:480-9. doi: 10.1016/j.neuropharm.2015.10.024. Epub 2015 Oct 23.

Abstract

Ginsenoside Rg1 (Rg1) is a major bioactive ingredient in Panax ginseng that has low toxicity and has been shown to have neuroprotective effects. The objectives of the present study were to explore the potential of the application of Rg1 for the treatment of Parkinson's disease (PD) and to determine whether its neuroprotective effects are exerted through the Wnt/β-catenin signaling pathway by using in vivo and in vitro models of PD. In the in vivo study, Rg1 treatment ameliorated the behavioral deficits of "Pole test", and reduced dopaminergic cell loss that were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) in a dose-dependent manner in an in vivo model of PD. In the in vitro study, cell viability was increased and cell apoptosis induced by 1-methyl-4-phenylpyridinium(MPP+) was decreased by Rg1 pretreatment. Rg1 induced protective effects on the protein and mRNA expression levels of markers of the Wnt/β-catenin signaling pathway in both the in vivo and the in vitro studies, and these neuroprotective effects were blocked by DKK1 in the in vitro study. Our results provide evidence that Rg1 has neuroprotective effects in both in vivo and in vitro PD models, and these effects act through the Wnt/β-catenin signaling pathway. Taken together, these results indicate that Rg1 may exert therapeutic effects on PD via the Wnt/β-catenin signaling pathway and may therefore provide a novel approach for the treatment of PD.

Keywords: Ginsenoside Rg1; Neurodegeneration; Neuroprotection; Parkinson's disease; Wnt/β-catenin signaling pathway.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Ginsenosides / pharmacology*
  • Ginsenosides / therapeutic use*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • In Situ Nick-End Labeling
  • MPTP Poisoning / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • PC12 Cells
  • RNA, Messenger / metabolism
  • Rats
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • Wnt Signaling Pathway / drug effects*
  • Wnt Signaling Pathway / genetics
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Ginsenosides
  • Neuroprotective Agents
  • RNA, Messenger
  • Wnt1 Protein
  • beta Catenin
  • Tyrosine 3-Monooxygenase
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • ginsenoside Rg1