Dual Beneficial Effects of (-)-Epigallocatechin-3-Gallate on Levodopa Methylation and Hippocampal Neurodegeneration: In Vitro and In Vivo Studies

摘要: 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 a COMT inhibitor highly beneficial controlling wearing-off phenomenon by improving L-DOPA bioavailability as well brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), common tea polyphenol, can serve naturally-occurring also possesses neuroprotective actions. Methodology/Principal Findings Using both vitro vivo models, we investigated modulating effects EGCG on methylation chemically induced oxidative neuronal damage degeneration. strongly inhibited human liver COMT-mediated O-methylation concentration-dependent manner vitro, with an average IC50 0.36 µM. Oral administration moderately lowered accumulation 3-O-methyldopa plasma striatum rats treated + carbidopa. In addition, reduced glutamate-induced cytotoxicity cultured HT22 mouse hippocampal cells through inactivation nuclear factor κB-signaling pathway. Under conditions, exerted strong protective effect against kainic acid-induced death hippocampus rats. Conclusions/Significance These observations suggest oral may significant patients exerting modest inhibition plus neuroprotection