Abstract：
Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer\'s disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-β oligomer (AβO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AβO-induced inflammation in BV2 cells through regulating IL-1β, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AβO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AβO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AβO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.
摘要：
神经炎症是认知功能障碍和神经退行性疾病如阿尔茨海默病(AD)的关键因素,因此抑制神经炎症被认为是AD的潜在治疗方法。表没食子儿茶素-3-没食子酸酯（EGCG），绿茶的多羟基酚，已经发现表现出抗氧化，抗炎和神经保护作用。本研究旨在探讨EGCG对炎症的抑制作用及其机制。在这项研究中,将BV2细胞同时暴露于脂多糖（LPS）和淀粉样蛋白-β寡聚体（AβO）以诱导炎症微环境。通过RT-PCR和WesternBlot检测炎性细胞因子和NLRP3炎性小体相关分子。结果表明,EGCG通过调节IL-1β抑制LPS/AβO诱导的BV2细胞炎症,IL-6和TNF-α。同时,EGCG减少了NOD的激活，LRR-,和含pyrin结构域蛋白3（NLRP3）炎症小体和BV2细胞内ROS的水平用LPS/AβO处理通过影响线粒体膜电位（MMP）。进一步研究发现EGCG通过调节LPS/AβO诱导的神经炎症中的硫氧还蛋白相互作用蛋白(TXNIP)抑制MMP。总之,EGCG可能通过抑制ROS/TXNIP/NLRP3通路减轻LPS/AβO诱导的小胶质神经炎症。它可能为EGCG减轻AD的抗炎特性提供潜在机制。
