Steiner Nicole, Balez Rachelle, Karunaweera Niloo, Lind Joanne M, Münch Gerald, Ooi Lezanne
Dept of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, Australia.
Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
Neurochem Int. 2016 May;95:46-54. doi: 10.1016/j.neuint.2015.10.013. Epub 2015 Oct 29.
Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8-B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation.
慢性炎症是神经退行性疾病的一个标志，一氧化氮（NO）的细胞毒性水平和促炎细胞因子可引发神经元死亡途径。使用一系列细胞实验，利用小鼠小胶质细胞（C8 - B4）、巨噬细胞（RAW264.7）和神经元样细胞系（Neuro2a）来评估白藜芦醇的抗炎和神经保护作用。我们通过格里斯试剂法检测NO的释放，并使用生物芯片阵列来测量一组促炎和抗炎细胞因子及趋化因子，以应对炎性刺激脂多糖（LPS）和干扰素 -γ（IFN -γ）。白藜芦醇是活化巨噬细胞和小胶质细胞中NO和细胞因子释放的有效抑制剂。在细胞培养中，随着预孵育时间延长，白藜芦醇的活性略有增强，这并非由于细胞毒性。使用NO供体，我们表明白藜芦醇可以保护Neuro2a细胞免受细胞毒性浓度NO的影响。在共培养实验中证实了白藜芦醇对RAW264.7细胞促炎信号的保护作用，从而提高了Neuro2a细胞的存活率。我们的数据共同表明白藜芦醇在亚硝化应激和神经炎症期间具有潜在的神经保护作用。
