Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies
- Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies
- 강기성; Wen Yujing; Yamabe Noriko; Fukui Masayuki; Bishop Stephanie; Zhu Bao Ting
- (-)-Epigallocatechin-3-gallate; Levodopa methylation; Neurodegeneration
- Issue Date
- PLOS ONE
- VOL 5, NO 8, e11951-1-e11951-14
- 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 naturallyoccurring
COMT inhibitor that also possesses neuroprotective actions.
Methodology/Principal Findings: 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 mM. 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 kB-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/Significance: 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.
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