Rhynchophylline Attenuates LPS-induced Pro-inflammatory Responses through Down-regulation of MAPK/NF-κB Signaling Pathways in Primary Microglia
Rhynchophylline Attenuates LPS-induced Pro-inflammatory Responses through Down-regulation of MAPK/NF-κB Signaling Pathways in Primary Microglia
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DOI：
10.1002/ptr.4614
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发表时间：
2012-10-01
影响因子：
7.2
通讯作者：
Ma, Shiping
中科院分区：
文献类型：
--
作者：
Song, Yu;Qu, Rong;Ma, Shiping
小胶质细胞的过度激活与各种类型的神经炎症有关。抑制小胶质细胞的激活将有治疗的好处，导致神经退行性疾病的进展的缓解。摘要本研究从钩藤属（Uncaria rhynchophylla, Miq.）中分离得到一种四环氧吲哚类生物碱，研究了钩藤碱（RIN）的抑制作用。杰克。在脂多糖（LPS）刺激的小胶质细胞中，研究了促炎介质的产生。结果表明，RIN显著降低了lps激活的小胶质细胞中一氧化氮（NO）、前列腺素E2 （PGE2）、单核细胞趋化蛋白（MCP-1）、肿瘤坏死因子-a （TNF-a）和白细胞介素-1 β (IL-1 β)的产生。iNOS和COX-2的mRNA表达水平也被RIN呈浓度依赖性地抑制。进一步研究发现，RIN阻断了iba的磷酸化和降解，抑制了丝裂原活化蛋白激酶（MAPKs）的磷酸化。综上所述，这些数据表明RIN抑制小胶质细胞的炎症反应，可能作为一种潜在的治疗药物，治疗各种涉及神经炎症的神经退行性疾病。版权所有：John Wiley & Sons， Ltd。
Excessive activation of microglial cells has been implicated in various types of neuroinflammation. Suppression of microglial activation would have therapeutic benefits, leading to the alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of rhynchophylline (RIN), a tetracyclic oxindole alkaloid component isolated from Uncaria rhynchophylla (Miq.) Jacks., on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated microglia. The results showed that RIN markedly reduced the production of nitric oxide (NO), prostaglandins E2 (PGE2), monocyte chemoattractant protein (MCP-1), tumor necrosis factor-a (TNF-a) and interleukin-1 beta (IL-1 beta) in LPS-activated microglia. The mRNA expression levels of iNOS and COX-2 were also depressed by RIN in a concentration-dependent manner. Further studies revealed that RIN blocked I Ba phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). In summary, these data suggest that RIN suppresses inflammatory responses of microglia and may act as a potential therapeutic agent for various neurodegenerative diseases involving neuroinflammation. Copyright (c) 2012 John Wiley & Sons, Ltd.