Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration.
Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration.
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DOI：
10.1016/j.brainres.2012.11.043
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发表时间：
2013-02-25
期刊：
影响因子：
2.9
通讯作者：
Zhu BT
中科院分区：
文献类型：
--
作者：
Kang KS;Yamabe N;Wen Y;Fukui M;Zhu BT
左旋多巴（L-DOPA）广泛用于帕金森病的对症治疗。我们最近发现，（−）-表没食子儿茶素-3-没食子酸酯，一种茶多酚，不仅能抑制左旋多巴甲基化，还能防止海马神经元的氧化性变性。在本研究中，我们试图确定其他几种常见的膳食酚类物质，即茶儿茶素[（+）-儿茶素和（-）-表儿茶素]和一种代表性的类黄酮（槲皮素），它们调节L-DOPA甲基化和保护海马免受氧化损伤的能力。使用体外生物化学测定、基于细胞培养的机制分析和体内动物模型的组合。虽然茶儿茶素和槲皮素在体外强烈抑制人肝儿茶酚-O-甲基转移酶（COMT）介导的L-DOPA的O-甲基化，但只有（+）-儿茶素在大鼠外周隔室和纹状体中对L-DOPA甲基化发挥显著抑制作用。与其他膳食化合物相比，（+）-儿茶素对L-DOPA甲基化的更强的体内作用是由于其更好的体内生物利用度。此外，（+）-儿茶素通过灭活核因子-κB信号通路，强烈降低谷氨酸诱导的体外HT 22小鼠海马神经元的氧化细胞毒性。在红藻氨酸诱导的大鼠海马神经元氧化变性模型中，（+）-儿茶素的给药也发挥了很强的神经保护作用。总之，（+）-儿茶素是一种膳食多酚，通过抑制左旋多巴甲基化和减少氧化性神经变性，可能对基于左旋多巴的帕金森病患者治疗产生有益影响。
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.
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DOI：
10.3233/jad-2009-1135
发表时间：
2009
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Ferruzzi MG;Lobo JK;Janle EM;Cooper B;Simon JE;Wu QL;Welch C;Ho L;Weaver C;Pasinetti GM
通讯作者：
Pasinetti GM
DOI：
10.1097/01.jnen.0000225906.82428.69
发表时间：
2006-07-01
影响因子：
3.2
作者：
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通讯作者：
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
14.5
作者：
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影响因子：
7.4
作者：
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