Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia
Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia
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DOI：
10.1016/j.lfs.2006.06.048
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发表时间：
2006-10-19
期刊：
影响因子：
6.1
通讯作者：
Kang, Seog Youn
中科院分区：
文献类型：
--
作者：
Jung, Ki Kyung;Lee, Hae Sung;Kang, Seog Youn
姜黄素已被证明具有抗炎、抗突变和抗癌活性。然而，姜黄素对引起神经元损伤的原代小胶质细胞（脑单核吞噬细胞）的功能激活的调节作用在很大程度上仍然未知。目前的研究检查了姜黄素是否影响大鼠原代小胶质细胞中NO的产生，并研究了其潜在的信号通路。姜黄素以剂量依赖性方式降低LPS刺激的小胶质细胞中NO的产生，IC 50值为3.7 μ M。它还抑制诱导型一氧化氮合酶（iNOS）的mRNA和蛋白水平，表明该药物可能影响iNOS基因表达过程。事实上，姜黄素改变了LPS诱导的生化模式，如所有促分裂原活化蛋白激酶（MAPK）的磷酸化，以及核因子-κ B（NF-κ B）和激活蛋白（AP）-1的DNA结合活性，通过报告基因测定进行评估。通过分析特异性MAPK抑制剂的抑制特性，发现c-Jun N-末端激酶（JNK）、p38和NF-κ B等一系列信号级联在姜黄素介导的小胶质细胞NO抑制中起关键作用。目前的研究结果表明，姜黄素是一个有前途的代理预防和治疗NO和小胶质细胞介导的神经退行性疾病。(c)2006年爱思唯尔公司All rights reserved.
Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the modulatory effect of curcumin on the functional activation of primary microglial cells, brain mononuclear phagocytes causing the neuronal damage, largely remains unknown. The current study examined whether curcumin influenced NO production in rat primary microglia and investigated its underlying signaling pathways. Curcumin decreased NO production in LPS-stimulated microglial cells in a dose-dependent manner, with an IC50 value of 3.7 mu M. It also suppressed both mRNA and protein levels of inducible nitric oxide synthase (iNOS), indicating that this drug may affect iNOS gene expression process. Indeed, curcumin altered biochemical patterns induced by LPS such as phosphorylation of all mitogen-activated protein kinases (MAPKs), and DNA binding activities of nuclear factor-kappa B (NF-kappa B) and activator protein (AP)-1, assessed by reporter gene assay. By analysis of inhibitory features of specific MAPK inhibitors, a series of signaling cascades including c-Jun N-terminal kinase (JNK), p38 and NF-kappa B was found to play a critical role in curcumin-mediated NO inhibition in microglial cells. The current results suggest that curcumin is a promising agent for the prevention and treatment of both NO and microglial cell-mediated neurodegenerative disorders. (c) 2006 Elsevier Inc. All rights reserved.