Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
Brain Res. 2020 Jun 1;1736:146730. doi: 10.1016/j.brainres.2020.146730. Epub 2020 Feb 18.
To investigate the neuroprotective effect of Gingko biloba extract 761 (EGb761) in Alzheimer's disease (AD) models both in vivo and in vitro and the underlying molecular mechanism.
Cultured BV2 microglial cells were treated with Aβ to establish an in vitro AD model. The in vivo rat AD model was established by injecting Aβ. 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.
Cultured BV2 cells exhibited prominent cell death after Aβ induction, 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.
Our 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.
研究银杏叶提取物 761（EGb761）在体内和体外阿尔茨海默病（AD）模型中的神经保护作用及其潜在的分子机制。
用 Aβ 处理培养的 BV2 小胶质细胞，建立体外 AD 模型。通过注射 Aβ 建立体内大鼠 AD 模型。用 EGb761 预处理细胞，分别通过 MTT 或流式细胞术检测细胞增殖和坏死情况。此外，还测量了膜电位和氧化应激。通过 Morris 水迷宫评估认知功能，并通过 Western blot 定量 JNK 信号通路的激活。
培养的 BV2 细胞在 Aβ 诱导后表现出明显的细胞死亡，而 EGb761 预处理可减轻这种细胞死亡。发现 EGb761 可减轻氧化应激，抑制膜电位和钙超载。EGb761 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体均显示 JNK 信号通路的激活，而 EGb761 可减轻细胞中的这种激活。
我们的结果表明，EGb761 通过调节细胞增殖、抑制坏死性凋亡和细胞凋亡、缓解线粒体损伤以及改善 AD 模型中的组织损伤来提高认知功能。所有这些作用可能都涉及 JNK 信号通路的抑制。
