Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways.
Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways.
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DOI：
10.3390/ijms19030821
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发表时间：
2018-03-12
影响因子：
5.6
通讯作者：
Fu S
中科院分区：
文献类型：
--
作者：
Chen G;Liu J;Jiang L;Ran X;He D;Li Y;Huang B;Wang W;Liu D;Fu S
以小胶质细胞活化为特征的神经炎症在帕金森病（PD）的发病机制中起着非常重要的作用。在激活时，促炎介质由小胶质细胞产生，引发过度的炎症反应并最终损害多巴胺能神经元。因此，识别抑制神经炎症的药物可能是开发PD新治疗方法的有效方法。在这项研究中，我们试图调查是否贝母素通过抑制神经炎症保护多巴胺能神经元。我们评估了贝母素乙对脂多糖（LPS）诱导的PD大鼠模型中的行为功能障碍、小胶质细胞活化和多巴胺能神经元丢失的影响。BV-2细胞用贝母素预处理1h后，再用LPS刺激不同时间。然后，分析炎症反应和相关的信号通路。在LPS诱导的PD大鼠模型中，贝母宁显著减轻行为功能障碍，并抑制多巴胺能神经元的丢失和小胶质细胞的活化。在BV-2细胞中，贝母素乙通过抑制ERK 1/2、AKT和NF-κB p65的磷酸化，显著降低LPS诱导的促炎介质TNF-α、IL-6和IL-1β、考克斯-2和iNOS的表达。以上结果表明，贝母素甲通过抑制神经炎症反应，对内毒素诱导的PD大鼠模型中的多巴胺能神经元具有保护作用。
Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson’s disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation. We evaluated the effects of peiminine on behavioural dysfunction, microglial activation and the loss of dopaminergic neurons in a rat model of lipopolysaccharide (LPS)-induced PD. BV-2 cells were pretreated with peiminine for 1 h and then stimulated with LPS for different times. Then, inflammatory responses and the related signalling pathways were analysed. Peiminine markedly attenuated behavioural dysfunction and inhibited the loss of dopaminergic neurons and microglial activation in the LPS-induced PD rat model. In BV-2 cells, peiminine significantly decreased LPS-induced expression of the pro-inflammatory mediators TNF-α, IL-6 and IL-1β, COX-2 and iNOS by inhibiting the phosphorylation of ERK1/2, AKT and NF-κB p65. Based on these results demonstrated that peiminine has a role in protecting dopaminergic neurons in the LPS-induced PD rat model by inhibiting neuroinflammation.
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影响因子：
5.6
作者：
Huang B;Liu J;Ju C;Yang D;Chen G;Xu S;Zeng Y;Yan X;Wang W;Liu D;Fu S
通讯作者：
Fu S
影响因子：
4.1
作者：
Hirsch, EC;Hunot, S;Hartmann, A
通讯作者：
Hartmann, A
GLP-2 通过抑制 ERK1/2、JNK1/2 和 NF-kappaB 信号通路减轻 BV-2 细胞中 LPS 诱导的炎症。
影响因子：
5.6
作者：
Li N;Liu BW;Ren WZ;Liu JX;Li SN;Fu SP;Zeng YL;Xu SY;Yan X;Gao YJ;Liu DF;Wang W
通讯作者：
Wang W
影响因子：
168.9
作者：
Kalia, Lorraine V.;Lang, Anthony E.
通讯作者：
Lang, Anthony E.
影响因子：
7.2
作者：
Song, Yu;Qu, Rong;Ma, Shiping
通讯作者：
Ma, Shiping