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

J Neurochem. 2001 Sep;78(5):1073-82. doi: 10.1046/j.1471-4159.2001.00490.x.

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 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.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Catalase / metabolism
  • Catechin / analogs & derivatives
  • Catechin / pharmacology*
  • Dopamine / physiology
  • Dopamine Agents
  • Flavonoids*
  • Free Radical Scavengers / pharmacology*
  • Immunohistochemistry
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monoamine Oxidase / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / metabolism
  • Neurons / drug effects
  • Neurons / enzymology
  • Oxidative Stress / drug effects
  • Phenols / pharmacology
  • Polymers / pharmacology
  • Rats
  • Superoxide Dismutase / metabolism
  • Tea / chemistry*
  • Tyrosine 3-Monooxygenase / analysis

Substances

  • Dopamine Agents
  • Flavonoids
  • Free Radical Scavengers
  • Phenols
  • Polymers
  • Tea
  • Catechin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • epigallocatechin gallate
  • Catalase
  • Tyrosine 3-Monooxygenase
  • Superoxide Dismutase
  • Monoamine Oxidase
  • Dopamine