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

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• 作者：Jianxin Liu^a ; ^b ; ^c ; ^{liujx3385@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Jinshan Tang^d ; ^{gztangjinshan@126.com" class="auth_mail" title="E-mail the corresponding author} ; Yihan Zuo^a ; ^b ; ^{zuoyihan521@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yang Yu^d ; ^{1018yuyang@163.com" class="auth_mail" title="E-mail the corresponding author} ; Pei Luo^a ; ^b ; ^{pluo@must.edu.mo" class="auth_mail" title="E-mail the corresponding author} ; Xinsheng Yao^d ; ^{tyaoxs@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Yan Dong^e ; ^{1462523594@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Peixun Wang^e ; ^{wpx@gzhtcm.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Liang Liu^a ; ^b ; ^{lliu@must.edu.mo" class="auth_mail" title="E-mail the corresponding author} ; Hua Zhou^a ; ^b ; ^{hzhou@must.edu.mo" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NO ; nitric oxide ; PGE2 ; prostaglandin E2 ; NSAIDs ; non-steroidal anti-inflammatory drugs ; qRT-PCR ; quantitative real-time polymerase chain reaction ; LPS ; lipopolysaccharide ; IFN-γ ; interferon γ ; G-CSF ; granulocyte colony stimulating factor ; TNF-α ; tumor necrosis factor-α ; IL-1β ; interleukin-1β ; IL-6 ; interleukin-6 ; MCP-1 ; monocyte chemoattractant protein-1 ; NF-κB ; Nuclear factor-κB ; IκB ; inhibitory protein ; IKK ; IκB kinase ; RPS3 ; ribosomal protein S3 ; iNOS ; inducible nitric oxide synthase ; COX-2
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：303-315
• 全文大小：3313 K

文摘

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.