Chrysophanol suppresses pro-inflammatory response in microglia via regulation of Drp1-dependent mitochondrial fission
Chrysophanol suppresses pro-inflammatory response in microglia via regulation of Drp1-dependent mitochondrial fission
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DOI：
10.1080/08923973.2017.1344988
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发表时间：
2017-01-01
影响因子：
3.3
通讯作者：
Lee, Dong-Seok
中科院分区：
文献类型：
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作者：
Chae, Unbin;Min, Ju-Sik;Lee, Dong-Seok
目的：大黄酚，也称为大黄酸，是一种在大黄中发现的天然蒽醌化合物。在古代东亚，掌叶红已被用于东方医学。小胶质细胞不仅代表中枢神经系统中最前沿的免疫防御，而且还是对各种威胁反应最灵敏的传感器。然而，激活的小胶质细胞可以通过过量产生细胞毒性分子和促炎细胞因子来发挥神经毒性作用。因此，调节小胶质细胞活化对于维持神经元功能非常重要。材料和方法：将BV-2胞壁小胶质细胞中的大黄酚预处理1小时，然后用1g/mL LPS刺激。通过蛋白质印迹和逆转录酶PCR检测蛋白质和RNA的水平。 DsRed2-Mito 表达细胞用于检测线粒体形态。结果：在本研究中，我们确定了大黄酚对脂多糖 (LPS) 诱导的小胶质细胞活化的影响。大黄酚通过抑制丝裂原激活蛋白激酶/核因子 kappa-B 激活和活性氧生成来抑制 LPS 诱导的促炎介质和细胞因子的产生。此外，大黄酚通过减少动力相关蛋白 1 (Drp1) 去磷酸化来下调 LPS 诱导的线粒体裂变。综上所述，大黄酚通过抑制 Drp1 依赖性线粒体分裂来抑制活化小胶质细胞的促炎反应。结论：我们的研究结果可以为大黄酚在小胶质细胞炎症反应介导的神经退行性疾病中的应用提供基础。此外，我们的研究可以通过纯化大黄酚来生产治疗炎症反应介导的神经退行性疾病的新药。
Objectives: Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function.Materials and methods: Pretreatment of chrysophanol in BV-2 murein microglial cells was carried out for 1 hour, followed by stimulation with 1g/mL LPS. Level of proteins and RNAs were detected by western blotting and Reverse Transcriptase PCR. DsRed2-Mito-expressing cells were used for detecting mitochondrial morphology.Results: In this study, we determined the effects of chrysophanol on lipopolysaccharide (LPS)-induced microglial activation. Chrysophanol inhibited the LPS-induced production of proinflammatory mediators and cytokines via suppression of mitogen-activated protein kinase/nuclear factor kappa-B activation and reactive oxygen species generation. In addition, chrysophanol downregulated LPS-induced mitochondrial fission by diminishing dynamin-related protein 1 (Drp1) dephosphorylation. Taken together, chrysophanol suppressed the proinflammatory response of activated microglia via inhibition of Drp1-dependent mitochondrial fission.Conclusion: Our findings can provide the basis for the use of chrysophanol in microglial inflammatory response-mediated neurodegenerative diseases. Furthermore, our study can contribute to the production of new drugs for inflammatory response-mediated neurodegenerative diseases by purification of chrysophanol.