Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model
Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model
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DOI：
10.1016/j.neuint.2012.03.011
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发表时间：
2012-06-01
影响因子：
4.2
通讯作者：
Yu, Deyue
中科院分区：
文献类型：
--
作者：
Qian, Yisong;Guan, Teng;Yu, Deyue
最近，中风的治疗集中在抗氧化疗法，其中涉及氧化应激。植物化合物对缺血性中风的预防和治疗潜力已被深入研究，因为它们中的许多含有抗氧化特性。染料木素是大豆中的活性成分之一，具有多种生物活性。在这项研究中，我们探讨了潜在的神经保护作用的染料木素及其可能的作用机制，在脑缺血小鼠模型。在进行短暂性大脑中动脉闭塞之前，用染料木黄酮（2.5、5和10 mg/kg）或溶媒每日一次口服预处理小鼠，连续14天。2.5-10 mg/kg剂量的Genistein可显著减少脑梗死体积，改善神经功能缺损，并防止缺血后细胞凋亡。此外，染料木黄酮预处理可抑制缺血诱导的活性氧（ROS）的产生，提高抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性，降低丙二醛（MDA）水平。此外，染料木黄酮逆转缺血后线粒体功能障碍，如通过降低线粒体ROS水平，阻止细胞色素C释放到细胞质和抑制caspase-3激活所证明的。Western blotting显示缺血激活了ROS依赖的核因子-κ B（NF-κ B）信号通路，而genistein抑制了NF-κ B p65亚基的磷酸化和激活，以及κ B α抑制蛋白（I κ B α）的磷酸化和降解。我们的研究结果表明，金雀异黄素在短暂局灶性脑缺血中具有神经保护作用，这可能涉及调节神经细胞凋亡途径和抑制ROS诱导的NF-κ B活化。(C)2012爱思唯尔有限公司保留所有权利。
Recently, the treatment of stroke has focused on antioxidant therapies, where oxidative stress is implicated. The preventive and therapeutic potential of plant compounds on ischemic stroke has been intensively studied because many of them contain antioxidant properties. Genistein, one of the active ingredients in soybean, possesses many bioactivities. In this study, we investigated the potential neuroprotective effects of genistein and its possible mechanism of action in a cerebral ischemia mouse model. Mice were pretreated with genistein (2.5, 5, and 10 mg/kg) or vehicle orally once daily for 14 consecutive days before transient middle cerebral artery occlusion was performed. Genistein at doses of 2.5-10 mg/kg significantly reduced the infarct volume, improved the neurological deficit and prevented cell apoptosis after ischemia. In addition, genistein pretreatment was shown to inhibit the ischemia-induced reactive oxygen species (ROS) production, enhance the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and decrease levels of malondialdehyde (MDA) in stroke mice. Moreover, genistein reversed the mitochondria dysfunction after ischemia, as evidenced by decreasing mitochondria ROS levels, preventing cytochrome C release to the cytoplasm and inhibiting caspase-3 activation. Western blotting showed ischemia activated the ROS-dependent nuclear factor-kappa B (NF-kappa B) signaling pathway, and genistein suppressed phosphorylation and activation of the NF-kappa B p65 subunit, as well as the phosphorylation and degradation of the inhibitor protein of kappa B alpha (I kappa B alpha). Our findings suggested that genistein has a neuroprotective effect in transient focal ischemia, which may involve regulation of mitochondria-dependent apoptosis pathways and suppression of ROS-induced NF-kappa B activation. (C) 2012 Elsevier Ltd. All rights reserved.