Andrographolide acts as an anti-inflammatory agent in LPS-stimulated RAW264.7 macrophages by inhibiting STAT3-mediated suppression of the NF-κB pathway
Andrographolide acts as an anti-inflammatory agent in LPS-stimulated RAW264.7 macrophages by inhibiting STAT3-mediated suppression of the NF-κB pathway
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DOI：
10.1016/j.jep.2011.03.068
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Lee, Tzung-Yan
中科院分区：
文献类型：
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作者：
Lee, Ko-Chen;Chang, Hen-Hong;Lee, Tzung-Yan
民族药理学意义：炎症涉及许多疾病，如慢性炎症性疾病和癌症。许多植物产品表现出有用的生物活性，包括抗真菌，抗细菌和抗炎作用。研究目的：然而，我们对穿心莲内酯的抗炎作用的理解是有限的。材料和方法：我们使用脂多糖（LPS）刺激的巨噬细胞作为炎症模型来研究穿心莲内酯的抗炎作用，其中含有多酚结构。我们发现穿心莲内酯具有很强的抗炎作用。本研究探讨穿心莲内酯对LPS诱导的RAW 264.7细胞一氧化氮合酶（NOS）和环氧合酶-2（考克斯-2）及其下游产物NO和PGE 2的抑制作用。穿心莲内酯治疗还降低了核因子-κ B（NF-κ B）和活化蛋白-1（AP-1）DNA结合活性。Western blot分析显示，穿心莲内酯显著抑制细胞信号转导和转录激活因子3（STAT 3）的磷酸化和CCAAT/增强子结合蛋白δ（C/EBP δ）的蛋白表达。我们还发现，穿心莲抑制LPS诱导的细胞因子信号转导抑制因子1和3（SOCS 1和3）mRNA的表达，这反过来又抑制细胞凋亡信号和线粒体膜电位激活。我们的研究结果表明，穿心莲内酯下调炎症诱导型一氧化氮合酶和考克斯-2基因的表达，通过抑制NF-κ B B和STAT 3的激活，通过干扰SOCS 1和SOCS 3 signaling.Conclusion的表达，因此，穿心莲内酯发挥了强大的抗炎作用，并可能被开发为一个有用的代理癌症或炎症性疾病的化学预防。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological significance: Inflammation is involved in numerous diseases, such as chronic inflammatory disease and cancer. Many plant products exhibit useful biological activities, including antifungal, antibacterial, and anti-inflammatory actions.Aim of study: However, our understanding of the anti-inflammatory effects of andrographolide is limited.Materials and methods: We use lipopolysaccharide (LPS)-stimulated macrophages as a model of inflammation to investigate the anti-inflammatory effects of andrographolide, which contains polyphenolic structures.Results: We found that andrographolide exhibited a potent anti-inflammatory effect. In this study, we investigated the inhibitory effects of andrographolide on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) as well as their respective downstream products, NO and PGE2, in RAW264.7 cells treated with LPS. Treatment with andrographolide also reduced nuclear factor-kappa B (NF-kappa B) and activation protein-1 (AP-1) DNA-binding activity. Western blot analysis showed that andrographolide significantly inhibited the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and the protein expression of CCAAT/enhancer-binding protein delta (C/EBP delta). We also found that andrographolide suppressed LPS-induced suppressor of cytokine signalling 1 and 3 (SOCS1 and 3) mRNA expression, which, in turn, inhibited apoptosis signalling and mitochondria membrane potential activation. Our results demonstrate that andrographolide downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-kappa B and STAT3 by interfering with the expression of SOCS1 and SOCS3 signalling.Conclusion: Therefore, andrographolide exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.