Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Bairro Santa Cecília, Porto Alegre, RS, 90035-003, Brazil.
Mol Neurobiol. 2018 Apr;55(4):2967-2978. doi: 10.1007/s12035-017-0510-x. Epub 2017 Apr 29.
Resveratrol is a natural polyphenol compound highly found in red wine that displays several beneficial effects on the central nervous system (CNS), preventing or slowing the progression of a wide variety of neurological diseases. Its neuroprotective role is particularly associated to modulation of antioxidant and anti-inflammatory responses in glial cells in a mechanism dependent of heme oxygenase 1 (HO-1) signaling pathway. Oligodendrocyte progenitor cells (OPC), primarily known for giving rise to mature oligodendrocytes, have emerged as dynamic cells that are also important to maintain the CNS homeostasis. In this sense, we have demonstrated that resveratrol has a protective effect on oligodendroglial functionality against lipopolysaccharide (LPS)-mediated cytotoxicity and that its glioprotective mechanism involves the nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 pathways. LPS, through toll-like receptor 4 (TLR4), affected the release of trophic factors by OPC, including transforming growth factor beta (TGF-β), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and resveratrol reestablished the trophic factor release to control levels. Additionally, resveratrol prevented the LPS-induced increase in the intracellular reactive oxygen species (ROS) as well as the decrease in glutathione (GSH) levels and in glutamate cysteine ligase (GCL) activity, through Nrf2/HO-1 signaling pathways. Resveratrol also prevented the increase of the transcriptional activities of nuclear factor κB (NFκB) and hypoxia-inducible factor 1 alpha (HIF-1α) after LPS challenge. In summary, this is the first study showing the glioprotective effect of resveratrol on oligodendroglial cells.
白藜芦醇是一种天然多酚化合物，在红酒中含量很高，对中枢神经系统（CNS）有多种有益作用，可预防或减缓多种神经退行性疾病的进展。其神经保护作用主要与胶质细胞抗氧化和抗炎反应的调节有关，这种调节依赖血红素加氧酶 1（HO-1）信号通路。少突胶质前体细胞（OPC）主要负责产生成熟的少突胶质细胞，但它们也是维持中枢神经系统内环境稳定的重要细胞。在这方面，我们已经证明白藜芦醇对脂多糖（LPS）介导的少突胶质细胞毒性具有保护作用，其神经保护机制涉及核因子红细胞 2 相关因子 2（Nrf2）和 HO-1 途径。LPS 通过 Toll 样受体 4（TLR4）影响 OPC 释放神经营养因子，包括转化生长因子-β（TGF-β）、脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF），而白藜芦醇将神经营养因子的释放恢复到控制水平。此外，白藜芦醇通过 Nrf2/HO-1 信号通路，防止 LPS 诱导的细胞内活性氧（ROS）增加以及谷胱甘肽（GSH）水平和谷氨酸半胱氨酸连接酶（GCL）活性降低。白藜芦醇还可防止 LPS 刺激后核因子 κB（NFκB）和缺氧诱导因子 1α（HIF-1α）转录活性的增加。总之，这是第一项表明白藜芦醇对少突胶质细胞具有神经保护作用的研究。
