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Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF‐I receptor signalling pathway
Author(s) -
Xu Li,
Chen WenFang,
Wong ManSau
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00361.x
Subject(s) - substantia nigra , tyrosine hydroxylase , dopamine transporter , dopaminergic , dopamine , apomorphine , medicine , nigrostriatal pathway , endocrinology , striatum , oxidopamine , neuroprotection , parkinson's disease , pars compacta , medial forebrain bundle , chemistry , pharmacology , disease
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.