Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2/iNOS and inactivation of NF-κB in lipopolysaccharide-stimulated macrophages
Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2/iNOS and inactivation of NF-κB in lipopolysaccharide-stimulated macrophages
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DOI：
10.1016/j.phymed.2016.03.016
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发表时间：
2016-07-15
期刊：
影响因子：
7.9
通讯作者：
Xiao, Jianbo
中科院分区：
文献类型：
--
作者：
Chen, Lei;Teng, Hui;Xiao, Jianbo
背景：仙鹤草内酯具有很强的抗炎活性，本研究旨在从分子水平上揭示其抗炎作用的潜在机制。假设/目的：探讨仙鹤草内酯的抗炎活性机制。研究设计：应用仙鹤草内酯在细胞内的抗炎活性。方法：利用脂多糖评价仙鹤草内酯的抗炎活性。 (LPS) 刺激 RAW 264.7 细胞模型。分别通过ELISA和亚硝酸盐分析测定IL-1β、IL-6、TNF-α和NO的产生。通过蛋白质印迹和RT-PCR分析检测iNOS和COX-2的表达。结果：仙鹤草内酯预处理显着降低促炎细胞因子（IL-1α、IL-6和TNF-α）的水平，并减弱LPS刺激的巨噬细胞中iNOS和COX-2的表达。此外，仙鹤草内酯还能抑制 LPS 刺激的巨噬细胞中 JNK 和 p38 MAPK 的激活，并降低 JAK-STAT 和 NF-κ B 的激活。结论：本研究表明，仙鹤草内酯至少部分通过抑制 LPS 诱导的 JAK-STAT 和 p38 MAPK 信号通路的激活来发挥抗炎活性。 (C) 2016 爱思唯尔有限公司。版权所有。
Background: Agrimonolide from Agrimonia pilosa showed a strong anti-inflammatory activity, and the present study aims to reveal potential mechanisms on molecular level explaining its anti-inflammatory effect.Hypothesis/Purpose: To investigate the mechanism of anti-inflammatory activity of agrimonolide.Study design: Anti-inflammatory activity of agrimonolide in cells was applied.Methods: Anti-inflammatory activity of agrimonolide isolated from Agrimonia pilosa was evaluated using lipopolysaccharide (LPS) stimulated RAW 264.7 cell models. The productions of IL-1 beta, IL-6, TNF-alpha and NO were determined by ELISA and nitrite analysis, respectively. The expressions of iNOS and COX-2 were measured by western blotting and RT-PCR analysis.Results: The pre-treatment with agrimonolide significantly reduced the levels of pro-inflammatory cytokines (IL-1 alpha, IL-6, and TNF-alpha), as well as attenuated the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, agrimonolide inhibited the activation of JNK and p38 MAPKs and decreased the activation of JAK-STAT and NF-kappa B in LPS-stimulated macrophages.Conclusion: The present study suggested that agrimonolide exerted anti-inflammatory activity, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signaling pathway. (C) 2016 Elsevier GmbH. All rights reserved.