EGb761 ameliorates cell necroptosis by attenuating RIP1-mediated mitochondrial dysfunction and ROS production in both in vivo and in vitro models of Alzheimer’s disease
EGb761 ameliorates cell necroptosis by attenuating RIP1-mediated mitochondrial dysfunction and ROS production in both in vivo and in vitro models of Alzheimer’s disease
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在阿尔茨海默病的体内和体外模型中，EGb761 通过减轻 RIP1 介导的线粒体功能障碍和 ROS 产生来改善细胞坏死性凋亡
DOI：
10.1016/j.brainres.2020.146730
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发表时间：
2020-02
期刊：
影响因子：
2.9
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Tu JL;Chen WP;Cheng ZJ;Zhang G;Luo QH;Li M;Liu X
目的探讨银杏叶提取物761（Gingko biloba extract 761，EGb 761）对阿尔茨海默病（Alzheimer's disease，AD）模型的神经保护作用及其分子机制。采用Aβ1-42注射法建立大鼠AD模型。用EGb 761预处理细胞，MTT法和流式细胞仪分别检测细胞增殖和凋亡情况。此外，膜电位和氧化应激进行了测量。Morris水迷宫检测认知功能，Western blotting检测JNK信号通路激活情况。结果Aβ1- 42诱导BV 2细胞死亡，EGb 761预处理可减轻Aβ1- 42诱导的BV 2细胞死亡。EGb 761可减轻氧化应激，抑制膜电位和钙超载。EGb 761治疗AD模型大鼠也改善了认知功能缺陷。培养的小胶质细胞和大鼠海马表现出JNK信号通路的激活，EGb 761缓解这种激活cells.ConclusionOur结果表明，EGb 761调节细胞增殖，抑制坏死性凋亡和凋亡，减轻线粒体损伤，改善组织损伤，提高AD模型的认知功能。所有这些作用可能涉及JNK信号通路的抑制。
ObjectivesTo investigate the neuroprotective effect of Gingko biloba extract 761 (EGb761) in Alzheimer’s disease (AD) models bothin vivoandin vitroand the underlying molecular mechanism.MethodsCultured BV2 microglial cells were treated with Aβ1-42to establish anin vitroAD model. Thein vivorat AD model was established by injecting Aβ1-42. Cells were pre-treated with EGb761, and the proliferation and necroptosis were examined by MTT or flow cytometry assays, respectively. In addition, the membrane potential and oxidative stress were measured. Cognitive function was evaluated by the Morris water maze, and the activation of the JNK signaling pathway was quantified by Western blotting.ResultsCultured BV2 cells exhibited prominent cell death after Aβ1-42induction, and this cell death was alleviated by EGb761 pre-treatment. EGb761 was found to relieve oxidative stress and suppress the membrane potential and calcium overload. EGb761 treatment in AD model rats also improved cognitive function deficits. Both cultured microglial cells and the rat hippocampus exhibited activation of the JNK signaling pathway, and EGb761 relieved this activation in cells.ConclusionOur results showed that EGb761 regulated cell proliferation, suppressed necroptosis and apoptosis, relieved mitochondrial damage, and ameliorated tissue damage to improve cognitive function in AD models. All of these effects may involve the suppression of the JNK signaling pathway.
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DOI：
10.1016/j.cca.2015.01.026
发表时间：
2015-12-07
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
--
作者：
Thornton C;Hagberg H
通讯作者：
Hagberg H
DOI：
--
发表时间：
2002
影响因子：
11.1
作者：
Yuan Luo;J. Smith;V. Paramasivam;Adam Burdick;K. Curry;Justin P Buford;I. Khan;William J. Netzer-William-J.
通讯作者：
Yuan Luo;J. Smith;V. Paramasivam;Adam Burdick;K. Curry;Justin P Buford;I. Khan;William J. Netzer-William-J.
影响因子：
16.6
作者：
Kucinski I;Dinan M;Kolahgar G;Piddini E
通讯作者：
Piddini E
影响因子：
15.1
作者：
Liu, Xu;Hao, Wenlin;Liu, Yang
通讯作者：
Liu, Yang
影响因子：
3.3
作者：
Meng, Xue-Lian;Chen, Chang-Lan;Lu, Jing
通讯作者：
Lu, Jing