Kang, Ki Sung Yamabe, Noriko Wen, Yujing Fukui, Masayuki Zhu, Bao Ting 2024-01-20T13:01:36Z 2024-01-20T13:01:36Z 2021-08-31 2013-02-25 0006-8993 https://pubs.kist.re.kr/handle/201004/128349 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-kappa B 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. (C) 2012 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV CATECHOL-O-METHYLTRANSFERASE RESERPINE-TREATED RAT PARKINSONS-DISEASE L-DOPA TEA CATECHINS HIPPOCAMPAL-NEURONS HEALTHY-VOLUNTEERS KAPPA-B PLASMA 3-O-METHYLDOPA Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration Article 10.1016/j.brainres.2012.11.043 1 BRAIN RESEARCH, v.1497, pp.1 - 14 BRAIN RESEARCH 1497 1 14 scie scopus 000315607500001 Neurosciences Neurosciences & Neurology Article CATECHOL-O-METHYLTRANSFERASE RESERPINE-TREATED RAT PARKINSONS-DISEASE L-DOPA TEA CATECHINS HIPPOCAMPAL-NEURONS HEALTHY-VOLUNTEERS KAPPA-B PLASMA 3-O-METHYLDOPA Levodopa Catechol-O-methyltransferase (COMT) (+)-Catechin Oxidative neuronal damage COMT inhibition Neuroprotection