Neuroprotective Effects of Jitai Tablet, a Traditional Chinese Medicine, on the MPTP-Induced Acute Model of Parkinson's Disease: Involvement of the Dopamine System.

Jia Liu,Yiyun Huang,Shaoang Tu,Shasha Xu,Jinlong Gao,Chenxin Gu,Mei Han,Ying Liu,Weihu Shang

doi:10.1155/2014/542383

Abstract

Jitai tablet (JTT) is a traditional Chinese medicine used to treat neuropsychiatric disorders. We previously demonstrated that JTT treatment led to increased level of dopamine transporter (DAT) in the striatum, thus indicating that JTT might have therapeutic potential for Parkinson's disease (PD), which is characterized by dysregulated dopamine (DA) transmission and decreased striatal DAT expression. The aim of this study was to investigate the neuroprotective effect of JTT on MPTP-induced PD mice. Using locomotor activity test and rotarod test, we evaluated the effects of JTT (0.50, 0.15, or 0.05 g/kg) on MPTP-induced behavioral impairments. Tyrosine hydroxylase TH-positive neurons in the substantia nigra and DAT and dopamine D2 receptor (D2R) levels in the striatum were detected by immunohistochemical staining and/or autoradiography. Levels of DA and its metabolites were determined by HPLC. In MPTP-treated mice, behavioral impairments were alleviated by JTT treatment. Moreover, JTT protected against impairment of TH-positive neurons and attenuated the MPTP-induced decreases in DAT and D2R. Finally, high dose of JTT (0.50 g/kg) inhibited the MPTP-induced increase in DA metabolism rate. Taken together, results from our present study provide evidence that JTT offers neuroprotective effects against the neurotoxicity of MPTP and thus might be a potential treatment for PD.

Highlights

Parkinson’s disease (PD) is a debilitating chronic and progressive neurodegenerative disease
We examined the effects of Jitai tablet (JTT) on behavioral changes and characteristics of the DA system in an MPTP-induced PD mouse model
MPTP treatment led to a significant reduction in dopamine transporter (DAT) binding in the striatum compared with control mice. This reduction was attenuated in mice treated with JTT, while treatment with Madopar showed no significant effect when compared to vehicle mice. These results indicate that JTT could significantly protect against MPTP-induced reductions in DAT levels in the mouse striatum and that JTT-H is more effective than Madopar

Summary

Introduction

Parkinson’s disease (PD) is a debilitating chronic and progressive neurodegenerative disease. A major treatment strategy for PD focuses on DA supplementation, through the use of DA precursors such as levodopa (L-DOPA) [4], DA receptor agonists, and monoamine oxidase B (MAO-B) inhibitors [1, 5]. Madopar, which is composed of the DA precursor L-DOPA and the decarboxylase inhibitor benserazide, is commonly used to treat PD by increasing DA concentrations. It is used for the relief of PD motor symptoms, it does not prevent or slow the progressive degeneration of neuronal cells and its long-term use may induce various side-effects including fluctuations and abnormalities in involuntary movements [6]. There is still an urgent need for efficacious therapies that act on the motor symptoms

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