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学科主题: 药学
题名:
Anti-Neuroinflammatory Effect of MC13, a Novel Coumarin Compound From Condiment Murraya, Through Inhibiting Lipopolysaccharide-Induced TRAF6-TAK1-NF-B, P38/ERK MAPKS and Jak2-Stat1/Stat3 Pathways
作者: Zeng, Ke-Wu1; Yu, Qian2; Liao, Li-Xi1; Song, Fang-Jiao2; Lv, Hai-Ning1; Jiang, Yong1; Tu, Peng-Fei1
关键词: NEUROINFLAMMATION ; MICROGLIA ; COUMARIN ; NF-B ; MAPK ; JAK ; STAT
刊名: JOURNAL OF CELLULAR BIOCHEMISTRY
发表日期: 2015-07-01
DOI: 10.1002/jcb.25084
卷: 116, 期:7, 页:1286-1299
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: NF-KAPPA-B ; ADJUVANT-INDUCED ARTHRITIS ; ISCHEMIC BRAIN-INJURY ; BV2 MICROGLIAL CELLS ; TOLL-LIKE RECEPTORS ; NATURAL COUMARIN ; OXIDATIVE DAMAGE ; ACTIVATION ; INFLAMMATION ; P38
英文摘要:

MC13 is a novel coumarin compound found in Murraya, an economic crop whose leaves are widely used as condiment (curry) in cuisine. The aims of the present study were to investigate the neuroprotective effects of MC13 on microglia-mediated inflammatory injury model as well as potential molecular mechanism. Cell viability and apoptosis assay demonstrated that MC13 was not toxic to neurons and significantly protected neurons from microglia-mediated inflammatory injury upon lipopolysaccharide (LPS) stimulation. Results showed that MC13 markedly inhibited LPS-induced production of various inflammatory mediators, including nitrite oxide (Griess method), TNF- and IL-6 (ELISA assay) in a concentration-dependent manner. Mechanism study showed that MC13 could suppress the activation of NF-B, which was the central regulator for inflammatory response, and also decreased the interaction of TGF--activated kinase 1 (TAK1)-binding protein (TAB2) with TAK1 and TNF receptor associated factor (TRAF6), leading to the decreased phosphorylation levels of NF-B upstream regulators such as IB and IB kinase (IKK). MC13 also significantly down-regulated the phosphorylation levels of ERK and p38 MAPKs, which played key roles in microglia-mediated inflammatory response. Furthermore, MC13 inhibited Jak2-dependent Stat1/3 signaling pathway activation by blocking Jak2 phosphorylation, Stat1/3 phosphorylation, and nuclear translocation. Taken together, our results demonstrated that MC13 protected neurons from microglia-mediated neuroinflammatory injury by inhibiting TRAF6-TAK1-NF-B, p38/ERK MAPKs, and Jak2-Stat1/3 pathways. Finally, MC13 might interact with LPS and interfere LPS-binding to cell membrane surface. These findings suggested that coumarin might act as a potential medicinal agent for treating neuroinflammation as well as inflammation-related neurodegenerative diseases. J. Cell. Biochem. 116: 1286-1299, 2015. (c) 2015 Wiley Periodicals, Inc.

语种: 英语
所属项目编号: 2012ZX09301002-002-002 ; 2012ZX09304-005 ; 81303253 ; 30873072 ; 81222051 ; 81473106
项目资助者: National Key Technology R&amp ; D Program "New Drug Innovation" of China ; Natural Science Foundation of China
WOS记录号: WOS:000354457900014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62826
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 1, Res Studio Integrat Tradit & Western Med, Beijing 100034, Peoples R China

Recommended Citation:
Zeng, Ke-Wu,Yu, Qian,Liao, Li-Xi,et al. Anti-Neuroinflammatory Effect of MC13, a Novel Coumarin Compound From Condiment Murraya, Through Inhibiting Lipopolysaccharide-Induced TRAF6-TAK1-NF-B, P38/ERK MAPKS and Jak2-Stat1/Stat3 Pathways[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2015,116(7):1286-1299.
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