The neuroprotective effects of tanshinone IIA on β-amyloid-induced toxicity in rat cortical neurons
The neuroprotective effects of tanshinone IIA on β-amyloid-induced toxicity in rat cortical neurons
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DOI：
10.1016/j.neuropharm.2010.08.013
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发表时间：
2010-12-01
影响因子：
4.7
通讯作者：
Hu, Hai-Tao
中科院分区：
文献类型：
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作者：
Liu, Tao;Jin, Hui;Hu, Hai-Tao
淀粉样β肽（A β）引起的氧化应激可能在阿尔茨海默病（AD）的发病机制中起重要作用。已知所有这些都直接负责活性氧（ROS）的产生和细胞凋亡的诱导。丹参酮IIA（Tan IIA）是从传统草药丹参BUNGE中提取的，已被证明可以防止氧化应激和细胞死亡。在这项研究中，我们研究了Tan IIA对A β（25-35）诱导的培养皮层神经元细胞死亡的神经保护作用。皮层神经元暴露于30 μ M A β（25-35）可引起明显的活力丧失、细胞凋亡、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性降低以及丙二醛（MDA）产生水平升高。同时，A β（25-35）显著增加细胞内ROS升高，降低线粒体膜电位（MMP）。然而，在A β（25-35）暴露前用Tan IIA预处理细胞明显抑制了这些A β（25-35）诱导的细胞事件。此外，Tan IIA降低A β（25-35）诱导的caspase-3活性增加，并减少细胞色素c从线粒体易位到胞质溶胶中。此外，Tan IIA还改善了A β（25-35）诱导的皮质神经元中Bcl-2/Bax比率的降低。总之，这些数据表明，Tan IIA通过其抗氧化潜力保护培养的皮层神经元免受A β（25-35）诱导的神经毒性。我们的研究结果强烈表明，谭IIA可能是有效的治疗与氧化应激相关的AD。(C)2010爱思唯尔有限公司版权所有。
Oxidative stress caused by amyloid beta-peptide (A beta) may play an important role in the pathogenesis of Alzheimer disease (AD). All is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. Tanshinone IIA (Tan IIA) is extracted from a traditional herbal medicine Salvia miltiorrhiza BUNGE, which has been shown to protect against oxidative stress and cell death. In this study, we investigated the neuroprotective effect of Tan IIA against A beta(25-35)-induced cell death in cultured cortical neurons. Exposure of cortical neurons to 30 mu M A beta(25-35) caused a significant viability loss, cell apoptosis and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA) production. In parallel, A beta(25-35) significant increased the intracellular ROS elevation and decreased mitochondrial membrane potential (MMP). However, pretreatment of the cells with Tan IIA prior to A beta(25-35) exposure suppressed these A beta(25-35)-induced cellular events noticeably. In addition, Tan IIA reduced the A beta(25-35)-induced increase of caspase-3 activity, and reduced cytochrome c translocation into the cytosol from mitochondria. Furthermore, Tan IIA also ameliorated the A beta(25-35)-induced Bcl-2/Bax ratio reduction in cortical neurons. Taken together, these data indicate that Tan IIA protected cultured cortical neurons against A beta(25-35)-induced neurotoxicity through its antioxidative potential. Our results strongly suggest that Tan IIA may be effective in treating AD associated with oxidative stress. (C) 2010 Elsevier Ltd. All rights reserved.