Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration

Brain Res. 2013 Feb 25;1497:1-14. doi: 10.1016/j.brainres.2012.11.043. Epub 2012 Dec 1.

Abstract

Levodopa (L-DOPA) is widely used for symptomatic management in Parkinson's disease. We recently showed that (-)-epigallocatechin-3-gallate, a tea polyphenol, not only inhibits L-DOPA methylation, but also protects against oxidative hippocampal neurodegeneration. In the present study, we sought to determine several other common dietary phenolics, namely, tea catechins [(+)-catechin and (-)-epicatechin] and a representative flavonoid (quercetin), for their ability to modulate L-DOPA methylation and to protect against oxidative hippocampal injury. A combination of in vitro biochemical assays, cell culture-based mechanistic analyses, and in vivo animal models was used. While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo. In addition, (+)-catechin strongly reduces glutamate-induced oxidative cytotoxicity in HT22 mouse hippocampal neurons in vitro through inactivation of the nuclear factor-κB signaling pathway. Administration of (+)-catechin also exerts a strong neuroprotective effect in the kainic acid-induced oxidative hippocampal neurodegeneration model in rats. In conclusion, (+)-catechin is a dietary polyphenolic that may have beneficial effects in L-DOPA-based treatment of Parkinson patients by inhibiting L-DOPA methylation plus reducing oxidative neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / blood
  • Carbidopa / pharmacology
  • Catechin / pharmacology*
  • Catechol O-Methyltransferase / metabolism*
  • Chromatography, High Pressure Liquid / methods
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dihydroxyphenylalanine / blood
  • Disease Models, Animal
  • Excitatory Amino Acid Agonists / toxicity
  • Fluoresceins
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / pathology*
  • Hydroxybenzoates / pharmacology*
  • In Vitro Techniques
  • Kainic Acid / toxicity
  • Levodopa / adverse effects
  • Levodopa / blood
  • Male
  • Methylation / drug effects
  • Mice
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / prevention & control*
  • Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reserpine / pharmacology
  • Time Factors
  • Tyrosine / analogs & derivatives

Substances

  • Adrenergic Uptake Inhibitors
  • Antiparkinson Agents
  • Excitatory Amino Acid Agonists
  • Fluoresceins
  • Glial Fibrillary Acidic Protein
  • Hydroxybenzoates
  • fluoro jade
  • Tyrosine
  • Levodopa
  • Dihydroxyphenylalanine
  • Reserpine
  • Catechin
  • Catechol O-Methyltransferase
  • phenolic acid
  • Carbidopa
  • Kainic Acid
  • 3-methoxytyrosine