Journal of Neurochemistry, Vol. 78, No. 5, 2001 1073-1082
© 2001


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

Yona Levites*, Orly Weinreb*, Gila Maor, Moussa B. H. Youdim* and Silvia Mandel*

* 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

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.

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.

Key Words: (–)-epigallocatechin-3-gallate – N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine – neurodegenerative diseases – oxidative stress – Parkinson's disease – polyphenols


Abbreviations used: BT, black tea; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; EGCG, (–)-epigalochatechin-3-gallate; GT, green tea; HVA, homovanillic acid; IL, interleukin; MPTP, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; OS, oxidative stress; PD, Parkinson's disease; ROS, reactive oxygen species; SNPC, substantia nigra pars compacta; TH, tyrosine hydroxylase; TNF- , tumor necrosis factor- ; SOD, superoxide dismutase; TO, turnover; XTT, 3'-{1-[(phenylamino)-carbonyl]-3,4-tetrazolium}-bis(4-methoxy-6-nitro)benzenesulfonic acid hydrate.