Li Rui, Huang Yuan-Gui, Fang Du, Le Wei-Dong
Health Science Center, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai Second Medical University, Shanghai, Peoples Republic of China.
J Neurosci Res. 2004 Dec 1;78(5):723-31. doi: 10.1002/jnr.20315.
Microglial activation is believed to play a pivotal role in the selective neuronal injury associated with several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down-regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG exerted significant protection against microglial activation-induced neuronal injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of microglial activation and thus is a useful candidate for a therapeutic approach to alleviating microglia-mediated dopaminergic neuronal injury in PD.
小胶质细胞激活被认为在与包括帕金森病(PD)和阿尔茨海默病在内的几种神经退行性疾病相关的选择性神经元损伤中起关键作用。我们提供的证据表明,绿茶多酚的主要单体(-)-表没食子儿茶素没食子酸酯(EGCG)通过下调诱导型一氧化氮合酶和肿瘤坏死因子-α(TNF-α)的表达,有效抑制脂多糖(LPS)激活的小胶质细胞分泌一氧化氮(NO)和肿瘤坏死因子-α(TNF-α)。此外,EGCG在人多巴胺能细胞系SH-SY5Y和原代大鼠中脑培养物中均对小胶质细胞激活诱导的神经元损伤发挥了显著的保护作用。我们的研究表明,EGCG是小胶质细胞激活的有效抑制剂,因此是缓解PD中小胶质细胞介导的多巴胺能神经元损伤治疗方法的有用候选物。