Rhein Suppresses Neuroinflammation via Multiple Signaling Pathways in LPS-Stimulated BV2 Microglia Cells
Rhein Suppresses Neuroinflammation via Multiple Signaling Pathways in LPS-Stimulated BV2 Microglia Cells
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大黄酸通过 LPS 刺激的 BV2 小胶质细胞中的多种信号通路抑制神经炎症
DOI：
10.1155/2020/7210627
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发表时间：
2020-06
影响因子：
--
通讯作者：
Wang Yang
中科院分区：
文献类型：
--
作者：
Zheng Piao;Tian Xuefei;Zhang Wei;Yang Zhaoyu;Zhou Jing;Zheng Jun;Cui Hanjin;Tang Tao;Luo Jiekun;Wang Yang
大黄酸作为大黄的一种生物活性吸收成分，在脑损伤的治疗中有着广泛的应用。然而，潜在的药理学机制仍不清楚。本研究旨在探讨大黄酸的体外抗神经炎作用及其机制。选择BV 2小胶质细胞，用LPS刺激。MTT法检测大黄酸对细胞活力的影响。通过免疫荧光染色、ELISA、RT-qPCR和western blot检测TNF-α和IL-1β的促炎细胞因子。此外，通过ELISA检测包括IL-6、IL-12、iNOS和IL-10的介质。Western blot检测PI 3 K/Akt、p38、ERK 1/2、TLR 4/NF-κB B蛋白表达水平。我们发现大黄酸可减少LPS激活的BV 2小胶质细胞中关键指标TNF-α和IL-1β的分泌，有效抑制其mRNA和蛋白的表达。此外，大黄酸处理降低了IL-6、IL-12和iNOS的产生，促进了IL-10的分泌。随后的机制实验表明，大黄酸明显下调PI 3 K、Akt、p38和ERK 1/2的磷酸化水平，同时上调PTEN的表达。此外，大黄酸还可拮抗TLR 4、p-IκBα和NF-κB的升高。总之，大黄酸通过多种信号通路（PI 3 K/Akt、p38、ERK 1/2和TLR 4/NF-κB）抑制LPS刺激的BV 2小胶质细胞中的神经炎症。这项研究强调了一种用于预防和治疗神经炎症的天然药物。
As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-α and IL-1β through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-α and IL-1β, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-IκBα, and NF-κB. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-κB) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.
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影响因子：
4.6
作者：
Yu C;Qi D;Sun JF;Li P;Fan HY
通讯作者：
Fan HY
影响因子：
5.8
作者：
Lu, Dah-Yuu;Liou, Houng-Chi;Fu, Wen-Mei
通讯作者：
Fu, Wen-Mei
影响因子：
9.3
作者：
Parajuli B;Sonobe Y;Kawanokuchi J;Doi Y;Noda M;Takeuchi H;Mizuno T;Suzumura A
通讯作者：
Suzumura A
DOI：
10.1007/978-1-4939-3299-3
发表时间：
2016
期刊：
--
影响因子：
--
作者：
Leonardo Salmena Vuk
通讯作者：
Leonardo Salmena Vuk
DOI：
--
发表时间：
2000
期刊：
Biochemistry. Biokhimiia
影响因子：
--
作者：
M. Krasilnikov
通讯作者：
M. Krasilnikov