Stauntoside B通过抑制NF-κB和ERK MAPK信号传导来抑制巨噬细胞活化。,Pharmacological Research

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Stauntoside B通过抑制NF-κB和ERK MAPK信号传导来抑制巨噬细胞活化。
Pharmacological Research ( IF 9.1 ) Pub Date : 2016-06-28 , DOI: 10.1016/j.phrs.2016.06.022
Jianxin Liu ₁ , Jinshan Tang ₂ , Yihan Zuo ₃ , Yang Yu ₂ , Pei Luo ₃ , Xinsheng Yao ₂ , Yan Dong ₄ , Peixun Wang ₄ , Liang Liu ₃ , Hua Zhou ₃

Affiliation

炎症是身体抵抗外来入侵的防御反应。然而，已经证明过度和持续的炎症反应导致各种炎性疾病，包括类风湿性关节炎。核因子-κB（NF-κB）调节活化的巨噬细胞中一系列炎症介质，细胞因子和趋化因子基因的表达。因此，NF-κB已成为控制炎症的有吸引力的药物靶标。在这项研究中，首次发现从中药Cynanchi Stauntonii中分离出的一种C21类固醇糖苷化合物stauntoside B，可以抑制脂多糖（LPS）诱导的RAW264.7细胞和大鼠原代腹膜巨噬细胞激活巨噬细胞。有效的NF-κB抑制剂。结果表明，山楂甙B显着降低了活化的RAW264.7细胞和大鼠腹膜巨噬细胞（包括一氧化氮（NO）和前列腺素E2（PGE2））中炎性介质的释放。促炎性介质和细胞因子的mRNA表达，包括诱导型一氧化氮合酶（iNOS），环氧合酶2（COX-2），微粒体前列腺素合成酶-1（mPGES-1），肿瘤坏死因子-α（TNF-α）。 stauntoside B也可抑制白细胞介素1β（IL-1β），白细胞介素6（IL-6）和单核细胞趋化蛋白1（MCP-1）以及TNF-α和IL-6的产生。机理研究表明，stauntoside B的抗炎活性可能是由于抑制LPS诱导的IKKα/β活化，IκBα磷酸化，p65（ser536）NF-κB磷酸化，在活化的巨噬细胞中，用Stauntoside B处理可激活ERK MAPK。同时，山楂甙B可以诱导LPS激活的巨噬细胞凋亡。目前的研究表明，山楂甙B是治疗炎性疾病，尤其是与NF-κB活化相关的炎性疾病的有价值的候选药物。

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Stauntoside B inhibits macrophage activation by inhibiting NF-κB and ERK MAPK signalling.

Inflammation is a defensive reaction of body to resist foreign invasion. However, it has been demonstrated that excessive and continuous inflammatory responses contribute to various inflammatory diseases, including rheumatoid arthritis. Nuclear factor-κB (NF-κB) regulates the expression of an array of inflammatory mediators, cytokines and chemokine genes in activated macrophages. Therefore, NF-κB has become an attractive drug target for controlling inflammation. In this study, stauntoside B, a C21 steroidal glycosides compound isolated from a Chinese medicine Cynanchi Stauntonii, was for the first time found to suppress macrophage activation induced by lipopolysaccharide (LPS) in RAW264.7 cells and rat primary peritoneal macrophages and could be a potent NF-κB inhibitor. The results showed that stauntoside B significantly reduced the release of inflammatory mediators in activated RAW264.7 cells and rat peritoneal macrophages, including nitric oxide (NO) and prostaglandin E2 (PGE2). The mRNA expressions of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), microsomal prostaglandin synthetase-1 (mPGES-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) as well as the production of TNF-α and IL-6 were also inhibited by stauntoside B. Mechanistic investigation implies that the anti-inflammatory activity of stauntoside B could result from the suppression of LPS-induced IKKα/β activation, IκBα phosphorylation, p65 (ser536) NF-κB phosphorylation, and ERK MAPK activation by stauntoside B treatment in activated macrophages. Meanwhile, stauntoside B could induce apoptosis in LPS-activated macrophages. The current study suggests stauntoside B being a valuable candidate drug for the treatment of inflammatory diseases, especially for NF-κB activation associated inflammatory diseases.

更新日期：2019-11-01

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