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

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.

• Authors: Li Xu, Wen-Fang Chen, Man-Sau Wong
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 158 Issue 3 Pg. 738-48 (Oct 2009) ISSN: 1476-5381 [Electronic] England
• PMID: 19703168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Plasma Membrane Transport Proteins
• Ginsenosides
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• Insulin-Like Growth Factor I
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Receptor, IGF Type 1
• ginsenoside Rg1
• Dopamine

Topics

• Animals
• Dopamine (metabolism)
• Dopamine Plasma Membrane Transport Proteins (biosynthesis)
• Female
• Ginsenosides (pharmacology)
• Insulin-Like Growth Factor I (physiology)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Oxidopamine
• Parkinson Disease, Secondary (chemically induced, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Rats
• Rats, Wistar
• Receptor, IGF Type 1 (antagonists & inhibitors)
• Signal Transduction
• Stereotyped Behavior (drug effects)
• Tyrosine 3-Monooxygenase (biosynthesis)