title: Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration.
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.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamabe
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wen
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukui
authors.forename: Bao Ting
authors.initials: BT
authors.lastname: Zhu
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000097:blood; D002230:Carbidopa / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D062385:Hydroxybenzoates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000633:toxicity; D007980:Levodopa / Q000009:adverse effects / Q000097:blood; D008297:Male; D008745:Methylation / Q000187:drug effects; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000978:Antiparkinson Agents; D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D062385:Hydroxybenzoates; C435731:fluoro jade; D014443:Tyrosine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D002392:Catechin; D002394:Catechol O-Methyltransferase; C017616:phenolic acid; D002230:Carbidopa; D007608:Kainic Acid; C008404:3-methoxytyrosine