title: Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies.
abstract: BACKGROUND
  A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.
  
  
  RESULTS
  Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.
  
  
  CONCLUSIONS
  These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wen
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukui
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Bishop
authors.forename: Bao Ting
authors.initials: BT
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008745:Methylation / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001688:Biological Products; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D007980:Levodopa; D002392:Catechin; C045651:epigallocatechin gallate; D007608:Kainic Acid