NF-κB Inhibitors Attenuate MCAO Induced Neurodegeneration and Oxidative Stress-A Reprofiling Approach (Retracted article. See vol. 16, 2023)
NF-κB Inhibitors Attenuate MCAO Induced Neurodegeneration and Oxidative Stress-A Reprofiling Approach (Retracted article. See vol. 16, 2023)
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核因子-κB抑制剂减轻大脑中动脉阻塞引起的神经变性和氧化应激--一种重塑方法(撤回文章。见2023年第16卷)
DOI：
10.3389/fnmol.2020.00033
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发表时间：
2020-03-24
影响因子：
4.8
通讯作者：
Li, Shupeng
中科院分区：
文献类型：
--
作者：
Ali, Awais;Shah, Fawad Ali;Li, Shupeng
中风是全球发病率和死亡率的主要原因。大约87%的中风病例是缺血性的，缺血性脑卒中扰乱了大脑的生理活动，从而导致一系列复杂的病理生理事件。尽管数十年来对神经保护剂的研究以探索针对缺血性中风的合适疗法，但尚未获得成功的结果，并且迫切需要新的替代方法来对抗这种病理折磨。为了解决这些问题，药物重新定位/重新配置被广泛探索。药物再利用旨在为已经建立的药物确定新的用途，这使其成为一种有吸引力的商业策略。核因子-κ β（NF-κ B B）参与了神经退行性变、神经炎症和缺血/再灌注损伤等多种生理和病理过程。在这项研究中，我们研究了阿托伐他汀、头孢氨苄和霉酚酸酯对缺血性卒中中NF-κ B的神经保护作用，并与标准NF-κ B抑制剂头孢酸苯乙酯（CAPE）进行了比较。进行计算机对接分析，并在体内短暂大脑中动脉闭塞（t-MCAO）大鼠模型中检查其潜在的神经保护活性。检查梗死面积百分比（%）和28分复合神经评分，并进一步进行免疫组织化学分析（IHC）和酶联免疫吸附测定（ELISA），以验证这些化合物在中风中的神经保护作用以及它们作为抗氧化剂的潜力。我们的研究结果表明，这些新的NF-κ B抑制剂可以通过靶向NF-κ B来减轻缺血性卒中诱导的神经元毒性，这是一种潜在的治疗缺血性卒中的方法。
Stroke is the leading cause of morbidity and mortality worldwide. About 87% of stroke cases are ischemic, which disrupt the physiological activity of the brain, thus leading to a series of complex pathophysiological events. Despite decades of research on neuroprotectants to probe for suitable therapies against ischemic stroke, no successful results have been obtained, and new alternative approaches are urgently required in order to combat this pathological torment. To address these problems, drug repositioning/reprofiling is explored extensively. Drug repurposing aims to identify new uses for already established drugs, and this makes it an attractive commercial strategy. Nuclear factor-kappa beta (NF-kappa B) is reported to be involved in many physiological and pathological conditions, such as neurodegeneration, neuroinflammation, and ischemia/reperfusion (I/R) injury. In this study, we examined the neuroprotective effects of atorvastatin, cephalexin, and mycophenolate against the NF-kappa B in ischemic stroke, as compared to the standard NF-kappa B inhibitor caeffic acid phenethyl ester (CAPE). An in-silico docking analysis was performed and their potential neuroprotective activities in the in vivo transient middle cerebral artery occlusion (t-MCAO) rat model was examined. The percent (%) infarct area and 28-point composite neuro score were examined, and an immunohistochemical analysis (IHC) and enzyme-linked immunosorbent assay (ELISA) were further performed to validate the neuroprotective role of these compounds in stroke as well as their potential as antioxidants. Our results demonstrated that these novels NF-kappa B inhibitors could attenuate ischemic stroke-induced neuronal toxicity by targeting NF-kappa B, a potential therapeutic approach in ischemic stroke.