Neuroprotective Effects Of Ginsenoside Rg1 On The Dopaminergic Neurons In The Substantia Nigra Of MPTP-Treated C57BL6 Mice

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterizedby selectively dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) andthe depletion of dopamine (DA) content in the striatum. Ginsenoside Rg1(Rg1) is one ofthe main components of ginseng, which has a variety of biological functions including butnot limited to anti-oxidative, estrogen-like activity. In the present study, effects of Rg1 on1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced dopamineregic neurondegeneration in the substantia nigra (SN) of C57BL6 mice were investigated. Byimmunohistochemistry (IHC), Perls' iron staining, semi-quantitive reversetranscriptase-polymerase chain reaction (RT-PCR), we detected the loss of dopamineneurons, the changes of the iron levels and the expressions of Caspase-3, Bcl-2 andBax in the SN, using HPLC, we observed the DA and its metabolites contents in theStriatum.The results were as follows:1. The numbers of TH immunoreactive neurons and the TH mRNA expressiondecreased in the SN of MPTP treated mice (P＜0.01, compared with that of control group).Pre-treatment with ginsenoside Rg1 reversed the above changes (P＜0.01).2. DA and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid(HVA) in the MPTP group decreased compared with the control group (P＜0.01). Theseeffects could partly be restored by Rg1(P＜0.01).3. Compared with the control group, the numbers of iron-staining cells increased in theSN of MPTP treated mice (P＜0.01). Pre-treatment with ginsenoside Rg1 reversed theabove changes (P＜0.01).4. Compared with the control group, the numbers of bcl-2 immunoreactive cells and thebcl-2 mRNA expression decreased in the SN of MPTP treated mice (P＜0.01). Pre-treatment with ginsenoside Rgl reversed the above changes (P＜0.01).5. Compared with the control group, the numbers of bax immunoreactive cells and thebax mRNA expression increased in the SN of MPTP treated mice (P＜0.01). Pre-treatmentwith ginsenoside Rg1 reversed the above changes (P＜0.01).6. Compared with the control group, the numbers of caspase-3 immunoreactive cellsand the caspase-3 mRNA expression increased in the SN of MPTP treated mice (P＜0.01).Pre-treatment with ginsenoside Rg1 reversed the above changes (P＜0.01).These results demonstrated that MPTP causes the dopaminergic neuron degenerationin the SN. Rg1 has neuroprotective effects against MPTP toxicities. The mechanismsunderlying Rg1 mediated neuroprotection maybe due to its anti-apoptotic and iron-chelator-like properties. These results provide experimental evidence for the clinicalapplication of Rg1 to prevent and treat PD.This project is supported by Department of Science & Technology of ShandongProvince (031070125) and the Bureau of Science and Technology of QingdaoMunicipal Government (04-2-JS-136, 05-10-JC-97)...