Abstract

Ampelopsis Radix, the root of Ampelopsis japonica (Thunb.) Makino (Vitaceae), is a herbal medicine which has been widely used in East Asia. The present study was done to explore whether the standardized extract of Ampelopsis Radix (AJW) protects dopaminergic neurons via antioxidant mechanisms in Parkinson's disease (PD) models. The effects of AJW on primary mesencephalic cultures stressed with 1-methyl-4-phenylpyridinium were investigated using tyrosine hydroxylase (TH) immunohistochemistry and reactive oxygen species measurement. The eliminative effects of AJW on the 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radicals were explored using colorimetric methods. The effects of AJW on the mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined by pole test as well as TH and 8-hydroxydeoxyguanosine immunohistochemistry. AJW protected dopaminergic neurons by inhibiting reactive oxygen species generation in vitro. Moreover, AJW showed potent radical scavenging activities in vitro. In the mouse PD model, AJW protected the dopaminergic neurons in the brain, leading to motor improvements. AJW inhibited the MPTP-evoked accumulation of 8-hydroxydeoxyguanosine in the brain. These data suggest that AJW has neuroprotective effects with antioxidant mechanisms in PD models.

Highlights

  • Oxidative stress occurs as a result of imbalance of the free radical generation and antioxidant defense system [1]

  • We demonstrated that AJW protects dopaminergic neurons against MPP+ toxicities in a primary culture system and against MPTP toxicities in mice through antioxidant mechanisms

  • To investigate whether AJW protects dopaminergic neurons from MPP+ toxicity, we performed an immunohistochemistry of tyrosine hydroxylase (TH), the crucial enzyme in dopamine biosynthesis [17], in primary cultured mesencephalic cells

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Summary

Introduction

Oxidative stress occurs as a result of imbalance of the free radical generation and antioxidant defense system [1]. Oxidative stress might contribute to the pathogenesis of Parkinson’s disease (PD), a common degenerative brain disease, which is featured by selective dopaminergic neurodegeneration from the SNc to the striatum and by clinical symptoms of bradykinesia, resting tremor, and rigidity [5]. Supporting this oxidative stress hypothesis, considerable levels of oxidative damaged macromolecules such as proteins, lipids, and DNA have been reported in PD brains [6]

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