Magnolol inhibits lipopolysaccharide-induced inflammatory response by interfering with TLR4 mediated NF-κB and MAPKs signaling pathways
Magnolol inhibits lipopolysaccharide-induced inflammatory response by interfering with TLR4 mediated NF-κB and MAPKs signaling pathways
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DOI：
10.1016/j.jep.2012.10.051
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发表时间：
2013-01-09
影响因子：
5.4
通讯作者：
Yang, Zhengtao
中科院分区：
文献类型：
--
作者：
Fu, Yunhe;Liu, Bo;Yang, Zhengtao
民族药理学意义：厚朴作为一种传统中草药，长期以来一直用于治疗焦虑、咳嗽、头痛和过敏性疾病，也被用于治疗包括抑郁症在内的多种精神障碍。研究目的：厚朴是从厚朴中分离出来的一种羟基联苯化合物，已有报道具有抗炎作用。然而，其潜在的分子机制还不是很清楚。本研究旨在探讨厚朴酚对脂多糖(LPS)诱导的RAW264.7细胞信号转导通路的影响及其分子机制。材料与方法：采用高效液相色谱法测定厚朴酚纯度。在加入或不加入厚朴酚的情况下，用脂多糖刺激RAW264.7细胞。用酶联免疫吸附试验和逆转录-聚合酶链式反应检测促炎症细胞因子的表达。Western印迹法检测核因子-kappaB、抑制性kappaB蛋白、p38、细胞外信号调节蛋白(ERK)、c-jun氨基末端激酶(JNK)和Toll样受体4(TLR4)的表达。对mTLR4和mMD2共转染的HEK293细胞进行进一步分析。结果：本研究所用厚朴酚纯度为100%。厚朴酚抑制脂多糖刺激的RAW264.7细胞中肿瘤坏死因子-α、IL-6和IL-1β的表达，并呈剂量依赖关系。Western印迹分析显示，厚朴酚可抑制脂多糖诱导的核因子-kappaB活化、I kappaBα降解、ERK、JNK和P38的磷酸化。厚朴酚可显著下调脂多糖刺激的TLR4的表达。结论：厚朴酚可能通过下调脂多糖上调的TLR4的表达而发挥抗炎作用，从而减弱TLR4介导的NF-kappa B和MAPK信号通路的激活以及促炎细胞因子的释放。这些发现表明，厚朴酚可能是一种抗炎症性疾病的治疗剂。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Ethnopharmacological relevance: Magnolia officinalis as a traditional Chinese herb has long been used for the treatment of anxiety, cough, headache and allergic diseases, and also have been used in traditional Chinese medicine to treat a variety of mental disorders including depression.Aim of the study: Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to have anti-inflammatory properties. However, the underlying molecular mechanisms are not well understood. The aim of this study was to investigate the molecular mechanism of magnolol in modifying lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 cells.Material and methods: The purity of magnolol was determined by high performance liquid chromatography. RAW264.7 cells were stimulated with LPS in the presence or absence of magnolol. The expression of proinflammartory cytokines were determined by ELISA and reverse transcription-PCR. Nuclear factor-kappa B (NF-kappa B), inhibitory kappa B (I kappa B alpha) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and Toll-like receptor 4 (TLR4) were determined by Western blot. Further analyses were performed on mTLR4 and mMD2 co-transfected HEK293 cells.Results: The result showed that the purity of magnolol used in this study was 100%. Magnolol inhibited the expression of TNF-alpha, IL-6 and IL-1 beta in LPS-stimulated RAW264.7 cells in a dose-dependent manner. Western blot analysis showed that magnolol suppressed LPS-induced NF-kappa B activation, I kappa B alpha, degradation, phosphorylation of ERK, JNK and P38. Magnolol could significantly down-regulated the expression of TLR4 stimulating by LPS. Furthermore, magnolol suppressed LPS-induced IL-8 production in HEK293-mTLR4/MD-2 cells.Conclusions: Our results suggest that magnolol exerts an anti-inflammatory property by down-regulated the expression of TLR4 up-regulated by LPS, thereby attenuating TLR4 mediated the activation of NF-kappa B and MAPK signaling and the release of pro-inflammatory cytokines. These findings suggest that magnolol may be a therapeutic agent against inflammatory diseases. (C) 2012 Elsevier Ireland Ltd. All rights reserved.