Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway

Li Xu, Wen Fang Chen, Man Sau Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

76 Citations (Scopus)

Abstract

Background and purpose: We have shown that ginsenoside Rg1 is a novel class of potent phytoestrogen and activates insulin-like growth factor-I receptor (IGF-IR) signalling pathway in human breast cancer MCF-7 cells. The present study tested the hypothesis that the neuroprotective actions of Rg1 involved activation of the IGF-IR signalling pathway in a rat model of Parkinson's disease, induced by 6-hydroxydopamine (6-OHDA). Experimental approach: Ovariectomized rats were infused unilaterally with 6-OHDA into the medial forebrain bundle to lesion the nigrostriatal dopamine pathway and treated with Rg1 (1.5 h after 6-OHDA injections) in the absence or presence of the IGF-IR antagonist JB-1 (1 h before Rg1 injections). The rotational behaviour induced by apomorphine and the dopamine content in the striatum were studied. Protein and gene expression of tyrosine hydroxylase, dopamine transporter and Bcl-2 in the substantia nigra were also determined. Key results: Rg1 treatment ameliorated the rotational behaviour induced by apomorphine in our model of nigrostriatal injury. This effect was partly blocked by JB-1. 6-OHDA significantly decreased the dopamine content of the striatum and treatment with Rg1 reversed this decrease. Treatment with Rg1 of 6-OHDA-lesioned rats reduced neurotoxicity, as measured by tyrosine hydroxylase, dopamine transporter and Bcl-2 protein and gene level in the substantia nigra. These effects were abolished by JB-1. Conclusions and implications: These data provide the first evidence that Rg1 has neuroprotective effects on dopaminergic neurons in the 6-OHDA model of nigrostriatal injury and its actions might involve activation of the IGF-IR signalling pathway.
Original languageEnglish
Pages (from-to)738-748
Number of pages11
JournalBritish Journal of Pharmacology
Volume158
Issue number3
DOIs
Publication statusPublished - 1 Oct 2009

Keywords

  • 6-hydroxydopamine
  • Dopaminergic system
  • Ginsenoside Rg1
  • Insulin-like growth factor-I receptor
  • Parkinson's disease

ASJC Scopus subject areas

  • Pharmacology

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