Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, 609-735, Republic of Korea.
Int Immunopharmacol. 2012 Sep;14(1):13-20. doi: 10.1016/j.intimp.2012.06.003. Epub 2012 Jun 20.
Amyloid β (Aβ) 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. Aβ-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 Aβ-induced expression and activation of MMP-9, iNOS, and COX-2, but not MMP-2. Ar-turmerone also reduced TNF-α, IL-1β, IL-6, and MCP-1 production in Aβ-stimulated microglial cells. Further, ar-turmerone markedly inhibited the production of ROS. Impaired translocation and activation of NF-κB were observed in Aβ-stimulated microglial cells exposed to ar-turmerone. Furthermore, ar-turmerone inhibited the phosphorylation and degradation of IκB-α as well as the phosphorylation of JNK and p38 MAPK. These results suggest that ar-turmerone impaired the Aβ-induced inflammatory response of microglial cells by inhibiting the NF-κB, 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.
淀粉样蛋白β（Aβ）诱导神经炎症分子的产生，这可能有助于许多神经退行性疾病的发病机制。因此，抑制神经炎症分子可能被开发为一种治疗方法。芳香（ar）-姜黄素，从姜黄中分离出的姜黄油，长期以来一直被东南亚用作药物和食品。在这项研究中，我们研究了 ar-姜黄素在 BV2 小胶质细胞中的抗炎作用。用 Aβ 刺激小胶质细胞，检测 MMP-9、iNOS 和 COX-2 的表达和激活、促炎细胞因子、趋化因子和 ROS 的产生，以及潜在的信号通路。ar-姜黄素显著抑制 Aβ诱导的 MMP-9、iNOS 和 COX-2 的表达和激活，但不抑制 MMP-2。ar-姜黄素还降低了 Aβ刺激的小胶质细胞中 TNF-α、IL-1β、IL-6 和 MCP-1 的产生。此外，ar-姜黄素明显抑制 ROS 的产生。在暴露于 ar-姜黄素的 Aβ 刺激的小胶质细胞中，观察到 NF-κB 的易位和激活受损。此外，ar-姜黄素抑制 IκB-α的磷酸化和降解以及 JNK 和 p38 MAPK 的磷酸化。这些结果表明，ar-姜黄素通过抑制 NF-κB、JNK 和 p38 MAPK 信号通路，损害了小胶质细胞中 Aβ诱导的炎症反应。最后，ar-姜黄素保护海马 HT-22 细胞免受激活的小胶质细胞间接诱导的神经元毒性。这些新发现为开发 ar-姜黄素作为治疗神经退行性疾病的治疗剂提供了新的见解。
