Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-κB and JNK/p38 MAPK pathways
Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-κB and JNK/p38 MAPK pathways
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DOI：
10.1016/j.intimp.2010.03.010
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发表时间：
2010-06-01
影响因子：
5.6
通讯作者：
Wang, Xue-Mei
中科院分区：
文献类型：
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作者：
Zeng, Ke-Wu;Fu, Hong;Wang, Xue-Mei
中枢神经系统(CNS)中的小胶质细胞在神经炎性反应的启动中起着重要作用。淫羊藿苷是淫羊藿中的一种化合物，已被报道对巨噬细胞系RAW264.7具有抗炎作用。然而，目前还不清楚淫羊藿苷在中枢神经系统中可能起到什么抗炎作用。在此，我们发现淫羊藿苷显著抑制脂多糖(LPS)激活的小胶质细胞一氧化氮(NO)、前列腺素E(PGE)-2、活性氧(ROS)的释放以及致炎细胞因子如肿瘤坏死因子(TNF)-α、白介素1-β(IL-1β)和白介素6(IL-6)的mRNA表达。淫羊藿苷还以剂量依赖方式抑制诱导型一氧化氮合酶(INOS)和环氧合酶(COX)-2的蛋白表达。进一步的机制研究表明淫羊藿苷阻断了TAK1/IKK/NF-kappa B和JNK/p38 MAPK通路。在神经元-小胶质细胞共培养体系中，淫羊藿苷可减轻脂多糖激活的小胶质细胞引起的皮质神经元变性。综上所述，这些发现为淫羊藿苷抑制脂多糖诱导的小胶质细胞神经炎性反应提供了机制方面的见解，并强调了淫羊藿苷在神经炎性疾病中的神经保护作用和治疗潜力。(C)2010爱思唯尔B.V.保留所有权利。
Microglia in the central nervous system (CNS) play an important role in the initiation of neuroinflammatory response. Icariin, a compound from Epimedium brevicornum Maxim, has been reported to have anti-inflammatory effect on the macrophage cell line RAW264.7. However, it is currently unknown what anti-inflammatory role icariin may play in the CNS. Here, we reported the discovery that icariin significantly inhibited the release of nitric oxide (NO), prostaglandin E (PGE)-2, reactive oxygen species (ROS) and mRNA expression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in lipopolysaccharide (LPS)-activated microglia. Icariin also inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Further mechanism studies revealed that icariin blocked TAK1/IKK/NF-kappa B and JNK/p38 MAPK pathways. It was also found that icariin reduced the degeneration of cortical neurons induced by LPS-activated microglia in neuron-microglia co-culture system. Taken together these findings provide mechanistic insights into the suppressive effect of icariin on LPS-induced neuroinflammatory response in microglia, and emphasize the neuroprotective effect and therapeutic potential of icariin in neuroinflammatory diseases. (C) 2010 Elsevier B.V. All rights reserved.