Anti-inflammatory effects of aromatic-turmerone through blocking of NF-kappa B, JNK, and p38 MAPK signaling pathways in amyloid beta-stimulated microglia

作者：Park Sun Young; Jin Mei Ling; Kim Young Hun; Kim YoungHee; Lee Sang Joon^*

来源：International Immunopharmacology, 2012, 14(1): 13-20.

DOI：10.1016/j.intimp.2012.06.003

• Ar-turmerone
• Amyloid beta
• Neuroinflammation
• Neuroprotection

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.

• 出版日期2012-9