Tetramethylpyrazine, a natural alkaloid, attenuates pro-inflammatory mediators induced by amyloid β and interferon-γ in rat brain microglia
Tetramethylpyrazine, a natural alkaloid, attenuates pro-inflammatory mediators induced by amyloid β and interferon-γ in rat brain microglia
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DOI：
10.1016/j.ejphar.2014.06.037
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发表时间：
2014-10-05
影响因子：
5
通讯作者：
Lee, Eunjoo H.
中科院分区：
文献类型：
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作者：
Kim, Mia;Kim, Sung-Ok;Lee, Eunjoo H.
神经炎一直被报道为阿尔茨海默病和其他神经退行性疾病的病理特征。小胶质细胞在多种病理刺激下被激活，在神经炎症的发生发展中起关键作用。淀粉样β蛋白(Aβ)是阿尔茨海默病大脑中淀粉样斑块的主要成分，已知可激活培养的小胶质细胞，产生更多的促炎和神经毒性因子。川芎中的主要生物活性生物碱为川芎(TMP)。IMP具有多种药理活性，包括抗氧化、抗炎、抗癌等作用。TMP的神经保护作用已在神经病理学的动物模型中得到证实。然而，该化合物对控制Aβ相关神经病理的疗效尚未被探索。我们检测了在干扰素-γ存在的情况下，IMP抑制Aβ(25-35)刺激培养的小胶质细胞的炎症反应的效果。TMP显著抑制Aβ(25-35)和干扰素-γ刺激的小胶质细胞产生一氧化氮、肿瘤坏死因子-α、白介素1-β、单核细胞趋化蛋白-1和细胞内活性氧。TMP还能有效降低Aβ(25-35)和干扰素-γ诱导的核因子-kappaB的活化。在器官型海马片培养(OHSCs)中，TMP显著阻断Aβ(25-35)诱导的活性氧生成和Akt的磷酸化。此外，TMP还可抑制Aβ(1-42)诱导的原代小胶质细胞产生的肿瘤坏死因子-α和1L-1β，以及OHSCs的神经元死亡。这些结果表明，TMP为缓解阿尔茨海默病的炎症进展提供了一种可能的治疗方法。(C)2014年爱思唯尔。版权所有。
Neuroinflammation has been consistently reported as a pathological hallmark of Alzheimer's disease and other neurodegenerative diseases. Microglial cells are activated by diverse pathological stimuli and play key roles in development of neuroinflammation. Amyloid beta peptide (A beta), the major constituent of amyloid plaques in Alzheimer's brain, is known to activate cultured microglial cells to produce increased amounts of proinflammatory and neurotoxic factors. Tetramethylpyrazine (TMP) is the main bioactive alkaloid isolated from Ligusticum chuanxiong. IMP has multiple pharmacological activities, including anti-oxidant, anti-inflammatory, and anti-cancer effects. Neuroprotective potential of TMP has been demonstrated in animal models of neuropathologies. However, the efficacy of this compound for controlling A beta-related neuropathology has not been explored yet. We examined the efficacy of IMP in the repression of inflammatory response in cultured microglial cells stimulated with A beta(25-35) in the presence of interferon (IFN)-gamma. TMP significantly inhibited the A beta(25-35) and IFN-gamma-stimulated productions of nitric oxide, tumor necrosis factor (TNF)-alpha, interleukin (lL)-1 beta, monocyte chemoattractant protein-1, and intracellular reactive oxygen species from primary microglial cells. TMP also effectively reduced A beta(25-35) and IFN-gamma-elicited NF-kappa B activation. In organotypic hippocampal slice cultures (OHSCs), TMP significantly blocked A beta(25-35)-induced reactive oxygen species generation and phosphorylation of Akt. Furthermore, TMP also inhibited A beta(1-42)-induced TNF-alpha and 1L-1 beta production in primary microglial cells and neuronal death in OHSCs. These results suggest that TMP provide a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer's disease. (C) 2014 Elsevier By. All rights reserved.