Green tea polyphenol (–)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 78, Issue 5, pages 1073–1082, September 2001
How to Cite
Levites, Y., Weinreb, O., Maor, G., Youdim, M. B. H. and Mandel, S. (2001), Green tea polyphenol (–)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. Journal of Neurochemistry, 78: 1073–1082. doi: 10.1046/j.1471-4159.2001.00490.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received April 3, 2001; revised manuscript received May 24, 2001; accepted June 12, 2001.
- neurodegenerative diseases;
- oxidative stress;
- Parkinson's disease;
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.