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标题：Citreorosein Inhibits Production of Proinflammatory Cytokines by Blocking Mitogen Activated Protein Kinases, Nuclear Factor-κB and Activator Protein-1 Activation in Mouse Bone Marrow-Derived Mast Cells
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作者：Yue Lu ; Seok-Jong Suh ; Xian Li 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：6
页码：938-945
DOI：10.1248/bpb.35.938
出版社：The Pharmaceutical Society of Japan
摘要：Citreorosein (CIT), an anthraquinone component of Polygoni cuspidati ( P. cuspidati ) radix, suppressed gene expression of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the molecular mechanisms underlying CIT inhibition of the pro-inflammatory cytokine production, its effects on the activation of both nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were assessed. CIT attenuated phosphorylation of the MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase and c-Jun NH₂-terminal kinase (JNK). Furthermore, CIT strongly inhibited DNA binding activity of NF-κB through the inhibition of phosphorylation and degradation of inhibitor of kappaB (IκB) as well as activator protein-1 (AP)-1 through the reduction of phosphorylation of c-Jun. These results demonstrate that CIT inhibits proinflammatory cytokines production through the inhibition of both MAPKs and AKT-mediated IκB kinase (IKK) phosphorylation and subsequent inhibition of transcription factor NF-κB activation, thereby attenuating the production of proinflammatory cytokines.
关键词：Citreorosein;proinflammatory cytokine;nuclear factor-κB;mitogen activated protein kinase;activator protein-1;mouse bone marrow-derived mast cell