Green tea polyphenol (–)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration

Authors

  • Yona Levites,

    1. *Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, and †Department of Cell Biology, Technion-Faculty of Medicine, Haifa, Israel
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  • Orly Weinreb,

    1. *Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, and †Department of Cell Biology, Technion-Faculty of Medicine, Haifa, Israel
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  • Gila Maor,

    1. *Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, and †Department of Cell Biology, Technion-Faculty of Medicine, Haifa, Israel
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  • Moussa B. H. Youdim,

    1. *Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, and †Department of Cell Biology, Technion-Faculty of Medicine, Haifa, Israel
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  • Silvia Mandel

    1. *Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research, and †Department of Cell Biology, Technion-Faculty of Medicine, Haifa, Israel
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Address correspondence and reprint requests to Professor M. B. H. Youdim, Department of Pharmacology, Technion- Faculty of Medicine, P.O.B. 9697, 31096 Haifa, Israel. E-mail: youdim@tx.technion.ac.il

Abstract

In the present study we demonstrate neuroprotective property of green tea extract and (–)-epigallocatechin-3-gallate in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin caused dopamine neuron loss in substantia nigra concomitant with a depletion in striatal dopamine and tyrosine hydroxylase protein levels. Pretreatment of mice with either green tea extract (0.5 and 1 mg/kg) or (–)-epigallocatechin-3-gallate (2 and 10 mg/kg) prevented these effects. In addition, the neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase (165%) activities, both effects being prevented by (–)-epigallocatechin-3-gallate. (–)-Epigallocatechin-3-gallate itself also increased the activities of both enzymes in the brain. The neuroprotective effects are not likely to be caused by inhibition of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine conversion to its active metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase-B, as both green tea and (–)-epigallocatechin-3-gallate are very poor inhibitors of this enzyme in vitro (770 µg/mL and 660 µM, respectively). Brain penetrating property of polyphenols, as well as their antioxidant and iron-chelating properties may make such compounds an important class of drugs to be developed for treatment of neurodegenerative diseases where oxidative stress has been implicated.

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