Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration.
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 microg/mL and 660 microM, 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.
Levites
Y
Y
Eve Topf, Technion-Faculty of Medicine, Haifa, Israel.
Weinreb
O
O
Maor
G
G
Youdim
M B
MB
Mandel
S
S
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents; D005419:Flavonoids; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015259:Dopamine Agents; D005419:Flavonoids; D016166:Free Radical Scavengers; D010636:Phenols; D011108:Polymers; D013662:Tea; D002392:Catechin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C045651:epigallocatechin gallate; D002374:Catalase; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase; D004298:Dopamine