NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of Astragaloside IV in LPS induced microglial cells
NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of Astragaloside IV in LPS induced microglial cells
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DOI：
10.1016/j.neulet.2017.12.039
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发表时间：
2018-02-14
影响因子：
2.5
通讯作者：
Yang, Tao
中科院分区：
文献类型：
--
作者：
Li, Congjin;Yang, Fanglin;Yang, Tao
黄芪甲苷（ASI）的抗神经炎症作用已有报道，但其机制尚不清楚。本研究旨在进一步探讨黄芪注射液抗LPS诱导的小胶质细胞神经炎症的作用机制。结果表明，ASI可显著降低BV 2和原代小胶质细胞中炎症介质NO、TNF-α和IL-6的产生。Western blot分析表明，ASI对MAPK的激活无抑制作用，而对ERK的激活有明显的诱导作用。我们还检测了NRF 2和HO-1的激活，这些激活被报道发挥抗神经炎症作用，结果表明它可以诱导BV 2小胶质细胞中HO-1下游NRF 2的激活。进一步的研究表明NRF 2/HO-1的激活是通过ERK途径实现的。NRF 2 siRNA或HO-1抑制剂处理后，ASI的抗神经炎作用较正常组明显减弱。综上所述，本研究表明，通过ERK信号通路激活NRF 2/HO-1是ASI在小胶质细胞中发挥抗神经炎症活性的一种新机制，它可能是一种有吸引力的调节脑内炎症反应的候选者。
The anti-neuroinflammatory effect of Astragaloside IV (ASI) has been reported, but its underlying mechanisms are unclear. This study is further to explore the underlying mechanism of ASI on anti-neuroinflammatory effect in LPS induced microglia cells. The result showed ASI significantly reduced the production of inflammatory mediators NO, TNF-alpha and IL-6 in BV2 and primary microglial cells. Western blot analysis showed ASI did not inhibit the MAPK activation, on the contrary, the results showed ASI can obviously induce the ERK activation. We also examined the NRF2 and HO-1 activation which were reported to exert anti-neuroinflammatory effect and the results presented it could induce the activation of HO-1 downstream NRF2 in BV2 microglial cells. Further study indicated the NRF2/HO-1 activation via ERK pathway activation. After NRF2 siRNA or HO-1 inhibitor treatment, the anti-neuroinflammatory effect of ASI was attenuated obviously compared with the normal group. Taken together, this study demonstrated that the activation of NRF2/HO-1 via ERK signaling pathway is a novel mechanism of ASI which exerted anti-neuroinflammatory activity in microglia cells, it could be an attractive candidate for the regulation of inflammatory responses in the brain.