五味子酯甲减轻活化小胶质细胞中的神经炎症：通过ERK磷酸化激活Nrf2的作用
Schisantherin A Attenuates Neuroinflammation in Activated Microglia: Role of Nrf2 Activation Through ERK Phosphorylation.
作者信息
Li Chuwen, Chen Tongkai, Zhou Hefeng, Zhang Chao, Feng Yu, Tang Fan, Hoi Maggie Pui-Man, He Chengwei, Zheng Ying, Lee Simon Ming-Yuen
机构信息
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
出版信息
Cell Physiol Biochem. 2018;47(5):1769-1784. doi: 10.1159/000491059. Epub 2018 Jun 28.
BACKGROUND/AIMS: In the present study, we investigated whether schisantherin A (StA) had anti-inflammatory effects under neuroinflammatory conditions.
METHODS
The effects of StA and its underlying mechanisms were examined in lipopolysaccharide (LPS)-activated BV-2 microglial cells by ELISA, qPCR, EMSA, Western blot, and IHC.
RESULTS
Firstly, we found that StA inhibited the inflammatory response in LPS-activated BV-2 microglia. Secondly, we found that StA suppressed LPS-induced activation of NF-κB via interfering with degradation of IκB and phosphorylation of IκB, IKK, PI3K/Akt, JNK, and p38 MAPK. Thirdly, StA conferred indirect antioxidative effects via quenching ROS and promoted expression of antioxidant enzymes, including HO-1 and NQO-1, via stimulating activation of Nrf2 pathways. Finally, we demonstrated that anti-neuroinflammatory actions of StA were dependent on ERK phosphorylation-mediated Nrf2 activation.
CONCLUSION
StA induced ERK phosphorylation-mediated Nrf2 activation, which contributed to its anti-inflammation and anti-oxidation. The anti-neuroinflammatory and anti-oxidative effects of StA may show preventive therapeutic potential for various neuroinflammatory disorders.
背景/目的：在本研究中，我们调查了五味子酯甲（StA）在神经炎症条件下是否具有抗炎作用。
方法
通过酶联免疫吸附测定（ELISA）、定量聚合酶链反应（qPCR）、电泳迁移率变动分析（EMSA）、蛋白质免疫印迹法（Western blot）和免疫组化法（IHC），在脂多糖（LPS）激活的BV-2小胶质细胞中检测StA的作用及其潜在机制。
结果
首先，我们发现StA抑制LPS激活的BV-2小胶质细胞中的炎症反应。其次，我们发现StA通过干扰IκB的降解以及IκB、IKK、PI3K/Akt、JNK和p38丝裂原活化蛋白激酶（MAPK）的磷酸化来抑制LPS诱导 的核因子κB（NF-κB）激活。第三，StA通过淬灭活性氧（ROS）赋予间接抗氧化作用，并通过刺激核因子E2相关因子2（Nrf2）途径的激活来促进抗氧化酶（包括血红素加氧酶-1（HO-1）和醌氧化还原酶1（NQO-1））的表达。最后，我们证明StA的抗神经炎症作用依赖于细胞外信号调节激酶（ERK）磷酸化介导的Nrf2激活。
结论
StA诱导ERK磷酸化介导的Nrf2激活，这有助于其抗炎和抗氧化作用。StA的抗神经炎症和抗氧化作用可能对各种神经炎症性疾病具有预防治疗潜力。
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