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标题：Mollugin Inhibits the Inflammatory Response in Lipopolysaccharide-Stimulated RAW264.7 Macrophages by Blocking the Janus Kinase-Signal Transducers and Activators of Transcription Signaling Pathway
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作者：Zheng-Guang Zhu ; Hong Jin ; Peng-Jiu Yu 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：2013
卷号：36
期号：3
页码：399-406
DOI：10.1248/bpb.b12-00804
出版社：The Pharmaceutical Society of Japan
摘要：Mollugin, a kind of naphthohydroquinone, is a major constituent isolated from Rubia cordifolia L. and demonstrated to possess anti-inflammatory activity in recent reports. However, the effects and mechanism of action of mollugin in inflammation have not been fully defined. The present study was therefore designed to investigate whether mollugin suppresses the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Mollugin attenuated the LPS-induced expression of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β and IL-6 but augmented the expression of tumor necrosis factor (TNF)-α. Mollugin did not inhibit the degradation of inhibitory kappa B (IκB)-α or the nuclear translocation of p65 nuclear factor-kappa B (NF-κB) but rather enhanced the phosphorylation of p65 subunits evoked by LPS. Mollugin did not inhibit the phosphorylation of extracellular-signal-related kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) 1/2 either. Mollugin significantly reduced the LPS-mediated phosphorylation of Janus kinase (JAK) 2, signal transducers and activators of transcription (STAT) 1 and STAT3. Molecular docking analysis showed that mollugin binds to JAK2 in a manner similar to that of AG490, a specific JAK2 inhibitor. We conclude that mollugin may be a JAK2 inhibitor and inhibits LPS-induced inflammatory responses by blocking the activation of the JAK-STAT pathway.
关键词：mollugin;macrophage;inflammatory mediator;Janus kinase-signal transducer and activator of transcription;nuclear factor-kappa B