汉黄芩素通过抑制TLR4-MyD88-TAK1介导的NF-κB和MAPK信号通路抑制脂多糖诱导的大鼠背根神经节神经元炎症反应。
Wogonin inhibits LPS-induced inflammatory responses in rat dorsal root ganglion neurons via inhibiting TLR4-MyD88-TAK1-mediated NF-κB and MAPK signaling pathway.
作者信息
Chen Shibiao, Xiong Jiangqin, Zhan Yanping, Liu Weicheng, Wang Xiuhong
机构信息
Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China,
出版信息
Cell Mol Neurobiol. 2015 May;35(4):523-31. doi: 10.1007/s10571-014-0148-4. Epub 2014 Dec 14.
Abstract
Recent studies showed that the activation of toll-like receptor 4 (TLR4) on dorsal root ganglion (DRG) neurons might underlie neuropathic and inflammatory pain states. This study was undertaken to investigate the effects of wogonin, a flavonoid with potent anti-inflammatory properties on the inflammatory reaction and TLR4 dependent pathways in lipopolysaccharide (LPS)-treated DRG neurons. Our results showed that wogonin not only inhibited the expression and interaction of TLR4, MyD88, and TAK1, but also reduced the activation of nuclear factor kappa B and mitogen-activated protein kinases pathway in LPS-treated DRG neurons. Moreover, wogonin significantly suppressed the release of pro-inflammatory mediators in LPS-induced DRG neurons, including cyclooxygenase-2, inducible nitric oxide synthases, interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha. Our results suggested that pre-treatment with wogonin could attenuate the TLR4-mediated inflammatory response in LPS-induced DRG neurons, thus might be beneficial for the treatment of neuropathic and inflammatory pain.
摘要
最近的研究表明，背根神经节（DRG）神经元上的Toll样受体4（TLR4）激活可能是神经性和炎性疼痛状态的基础。本研究旨在探讨汉黄芩素（一种具有强大抗炎特性的黄酮类化合物）对脂多糖（LPS）处理的DRG神经元炎症反应和TLR4依赖性途径的影响。我们的结果表明，汉黄芩素不仅抑制了TLR4、髓样分化因子88（MyD88）和转化生长因子β激活激酶1（TAK1）的表达和相互作用，还降低了LPS处理的DRG神经元中核因子κB和丝裂原活化蛋白激酶途径的激活。此外，汉黄芩素显著抑制了LPS诱导的DRG神经元中促炎介质的释放，包括环氧合酶-2、诱导型一氧化氮合酶、白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α。我们的结果表明，用汉黄芩素预处理可减弱LPS诱导的DRG神经元中TLR4介导的炎症反应，因此可能对神经性和炎性疼痛的治疗有益。
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