Anti-inflammatory effects of aromatic-turmerone through blocking of NF-κB, JNK, and p38 MAPK signaling pathways in amyloid β-stimulated microglia
Anti-inflammatory effects of aromatic-turmerone through blocking of NF-κB, JNK, and p38 MAPK signaling pathways in amyloid β-stimulated microglia
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DOI：
10.1016/j.intimp.2012.06.003
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发表时间：
2012-09-01
影响因子：
5.6
通讯作者：
Lee, Sang Joon
中科院分区：
文献类型：
--
作者：
Park, Sun Young;Jin, Mei Ling;Lee, Sang Joon
淀粉样蛋白β（A β）诱导神经炎性分子的产生，这可能有助于许多神经退行性疾病的发病机制。因此，抑制神经炎性分子可以被开发为一种治疗方法。芳香（ar）-姜黄酮，从姜黄中分离出来的姜黄油，长期以来在东南亚被用作药物和食品。在这项研究中，我们研究了ar-turmerone在BV 2小胶质细胞中的抗炎作用。测试β刺激的小胶质细胞的MMP-9、iNOS和考克斯-2的表达和活化，促炎细胞因子、趋化因子和ROS的产生，以及潜在的信号传导途径。Artumerone显著抑制A β诱导的MMP-9、iNOS和考克斯-2的表达和活化，但不抑制MMP-2。在A β刺激的小胶质细胞中，Ar-turmerone还减少TNF-α、IL-1 β、IL-6和MCP-1的产生。此外，ar-turmerone显着抑制ROS的产生。在A β刺激的小胶质细胞中观察到NF-κ B的易位和活化受损。此外，ar-turmerone抑制I κ B-α的磷酸化和降解以及JNK和p38 MAPK的磷酸化。这些结果表明，阿姜酮通过抑制NF-κ B B、JNK和p38 MAPK信号通路来损害A β诱导的小胶质细胞的炎症反应。最后，ar-turmerone保护海马HT-22细胞免受激活的小胶质细胞诱导的间接神经元毒性。这些新的发现提供了新的见解的发展，作为一种治疗剂，用于治疗神经退行性疾病的art-turmerone。(C)2012 Elsevier B. V.保留所有权利。
Amyloid beta (A beta) induces the production of neuroinflammatory molecules, which may contribute to the pathogenesis of numerous neurodegenerative diseases. Therefore, suppression of neuroinflammatory molecules could be developed as a therapeutic method. Aromatic (ar)-turmerone, turmeric oil isolated from Curcuma longa, has long been used in Southeast Asia as both a remedy and a food. In this study, we investigated the anti-inflammatory effects of ar-turmerone in BV2 microglial cells. A beta-stimulated microglial cells were tested for the expression and activation of MMP-9, iNOS, and COX-2, the production of proinflammatory cytokines, chemokines, and ROS, as well as the underlying signaling pathways. Ar-turmerone significantly suppressed A beta-induced expression and activation of MMP-9, iNOS, and COX-2, but not MMP-2. Ar-turmerone also reduced TNF-alpha, IL-1 beta, IL-6, and MCP-1 production in A beta-stimulated microglial cells. Further, ar-turmerone markedly inhibited the production of ROS. Impaired translocation and activation of NF-kappa B were observed in A beta-stimulated microglial cells exposed to ar-turmerone. Furthermore, ar-turmerone inhibited the phosphorylation and degradation of I kappa B-alpha as well as the phosphorylation of JNK and p38 MAPK. These results suggest that ar-turmerone impaired the A beta-induced inflammatory response of microglial cells by inhibiting the NF-kappa B, JNK, and p38 MAPK signaling pathways. Lastly, ar-turmerone protected hippocampal HT-22 cells from indirect neuronal toxicity induced by activated microglial cells. These novel findings provide new insights into the development of ar-turmerone as a therapeutic agent for the treatment of neurodegenerative disorders. (C) 2012 Elsevier B.V. All rights reserved.