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晚期糖基化终末产物(AGE)及其成分对神经炎症和神经退行性变的保护作用。

Protective Effects of AGE and Its Components on Neuroinflammation and Neurodegeneration.

作者信息

Qu Zhe, Mossine Valeri V, Cui Jiankun, Sun Grace Y, Gu Zezong

机构信息

Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, M263 Medical Science Building, One Hospital Drive, Columbia, MO, 65212, USA.

Center for Translational Neuroscience, University of Missouri School of Medicine, Columbia, MO, 65212, USA.

出版信息

Neuromolecular Med. 2016 Sep;18(3):474-82. doi: 10.1007/s12017-016-8410-1. Epub 2016 Jun 4.

DOI:10.1007/s12017-016-8410-1
PMID:27263111
Abstract

Garlic (Allium sativum) is used for culinary and medicinal purposes in diverse cultures worldwide. When fresh garlic is soaked in aqueous ethanol under ambient environment over 4 months or longer, the majority of irritating taste and odor is eliminated and the antioxidant profile in the resulting aged garlic extract (AGE) changes significantly. Recently, AGE and its components have been demonstrated to exert neuroprotective effects in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. Because of its health supporting potential, there is increasing interest in understanding the antioxidant and anti-inflammatory properties and the underlying mechanisms for its protective effects in heath and disease. There is evidence for AGE to exert its action on distinct signaling pathways associated with oxidative stress and neuroinflammation, although the primary molecular mechanisms remain unclear. By utilizing quantitative proteomic approaches, we demonstrated that AGE and two of its major ingredients, S-allyl-L-cysteine and N (α)-(1-deoxy-D-fructos-1-yl)-L-arginine, can attenuate neuroinflammatory responses in microglial cells through modulation of Nrf2-mediated signaling as well as other oxidative stress-related pathways. These experimental data provide information for the molecular targets of AGE and its components to mitigate neurodegeneration and neuroinflammation and show a promising potential of these compounds as dietary supplements for health maintenance.

摘要

大蒜(Allium sativum)在世界各地的不同文化中用于烹饪和药用。当新鲜大蒜在环境条件下于含水乙醇中浸泡4个月或更长时间时,大部分刺激性味道和气味会被去除,并且所得的陈年大蒜提取物(AGE)中的抗氧化成分会发生显著变化。最近,AGE及其成分已被证明在包括阿尔茨海默病、帕金森病、亨廷顿病和脑缺血在内的神经退行性疾病中发挥神经保护作用。由于其对健康的支持潜力,人们对了解其抗氧化和抗炎特性及其在健康和疾病中发挥保护作用的潜在机制的兴趣日益增加。有证据表明AGE对与氧化应激和神经炎症相关的不同信号通路发挥作用,尽管主要分子机制仍不清楚。通过使用定量蛋白质组学方法,我们证明AGE及其两种主要成分S-烯丙基-L-半胱氨酸和N(α)-(1-脱氧-D-果糖-1-基)-L-精氨酸可以通过调节Nrf2介导的信号通路以及其他氧化应激相关途径来减轻小胶质细胞中的神经炎症反应。这些实验数据为AGE及其成分减轻神经退行性变和神经炎症的分子靶点提供了信息,并显示出这些化合物作为维持健康的膳食补充剂的潜在前景。

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