Cheng-Chung Wei James, Huang Hsiu-Chen, Chen Wei-Jen, Huang Chien-Ning, Peng Chiung-Huei, Lin Chih-Li
Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Integrative Medicine, China Medical University, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
Eur J Pharmacol. 2016 Jan 5;770:16-24. doi: 10.1016/j.ejphar.2015.11.048. Epub 2015 Nov 28.
Microglia are the primary immune cells that contribute to neuroinflammation by releasing various proinflammatory cytokines and neurotoxins in the brain. Microglia-mediated neuroinflammation is one of the key characteristics of Alzheimer's disease (AD). Therefore, inhibitory reagents that prevent microglial activation may be used as potential therapeutic agents for treating AD. Recently, many studies have been performed to determine the bioactivities of green tea polyphenol epigallocatechin-3-gallate (EGCG), an efficient antioxidant that prevents neuroinflammation. However, limited information is available on the effects of EGCG on microglia-mediated neuroinflammation. In this study, we investigated the inhibitory effects of EGCG on amyloid β (Aβ)-induced microglial activation and neurotoxicity. Our results indicated that EGCG significantly suppressed the expression of tumor necrosis factor α (TNFα), interleukin-1β, interleukin-6, and inducible nitric oxide synthase (iNOS) in Aβ-stimulated EOC 13.31 microglia. EGCG also restored the levels of intracellular antioxidants nuclear erythroid-2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thus inhibiting reactive oxygen species-induced nuclear factor-κB (NF-κB) activation after Aβ treatment. Furthermore, EGCG effectively protected neuro-2a neuronal cells from Aβ-mediated, microglia-induced cytotoxicity by inhibiting mitogen-activated protein kinase-dependent, Aβ-induced release of TNFα. Taken together, our findings suggested that EGCG suppressed Aβ-induced neuroinflammatory response of microglia and protected against indirect neurotoxicity. These results suggest that EGCG is a possible therapeutic agent for preventing Aβ-induced inflammatory neurodegeneration.
小胶质细胞是主要的免疫细胞，通过在大脑中释放各种促炎细胞因子和神经毒素来引发神经炎症。小胶质细胞介导的神经炎症是阿尔茨海默病（AD）的关键特征之一。因此，阻止小胶质细胞激活的抑制性试剂可能用作治疗AD的潜在治疗药物。最近，已经进行了许多研究来确定绿茶多酚表没食子儿没食子酸酯（EGCG）的生物活性，EGCG是一种有效的抗氧化剂，可预防神经炎症。然而，关于EGCG对小胶质细胞介导的神经炎症的影响的信息有限。在本研究中，我们研究了EGCG对淀粉样β（Aβ）诱导的小胶质细胞激活和神经毒性的抑制作用。我们的结果表明，EGCG显著抑制了Aβ刺激的EOC 13.31小胶质细胞中肿瘤坏死因子α（TNFα）、白细胞介素-1β、白细胞介素-6和诱导型一氧化氮合酶（iNOS）的表达。EGCG还恢复了细胞内抗氧化剂核红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的水平，从而抑制了Aβ处理后活性氧诱导的核因子-κB（NF-κB）激活。此外，EGCG通过抑制丝裂原活化蛋白激酶依赖性的、Aβ诱导的TNFα释放，有效地保护神经2a神经元细胞免受Aβ介导的、小胶质细胞诱导的细胞毒性。综上所述，我们的研究结果表明，EGCG抑制了Aβ诱导的小胶质细胞神经炎症反应，并预防了间接神经毒性。这些结果表明，EGCG是预防Aβ诱导的炎症性神经退行性变的一种可能的治疗药物。
