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Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways.

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WOS被引频次:106
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成果类型:
期刊论文
作者:
Dai, Ji-Nan;Zong, Yi;Zhong, Lian-Mei;Li, Yue-Min;Zhang, Wei;Bian, Li-Gong;Ai, Qing-Long;Liu, Yi-Dan;Sun, Jun;Lu, Di
通讯作者:
Dai, JN
作者机构:
[Bian, Li-Gong; Li, Yue-Min; Dai, Ji-Nan; Sun, Jun; Lu, Di; Zong, Yi] Kunming Med Univ, Dept Anat, Kunming, Yunnan, Peoples R China.
[Zhong, Lian-Mei; Zhang, Wei; Ai, Qing-Long] Kunming Med Univ, Affiliated Hosp 1, Dept Neurol, Kunming, Yunnan, Peoples R China.
[Lu, Di] Kunming Med Univ, Rehabil Engn Res Lab, Biomed Engn Res Ctr, Kunming, Yunnan, Peoples R China.
[Liu, Yi-Dan] Kunming Pharmaceut Corp, Kunming, Yunnan, Peoples R China.
通讯机构:
[Dai, JN] Kunming Med Univ, Dept Anat, Kunming, Yunnan, Peoples R China.
语种:
英文
期刊:
PLOS ONE
ISSN:
1932-6203
年:
2011
卷:
6
期:
7
页码:
e21891
文献类别:
WOS:Article
所属学科:
ESI学科类别:神经系统学&行为学;WOS学科类别:Multidisciplinary Sciences
入藏号:
WOS:000292699000014;PMID:21765922
基金类别:
National Natural Sciences Foundation of China [30860336, 30560170]; Department of Science and Technology of Yunnan Province [2008CC007, 2009CI033]; Department of Science and Technology of Yunnan Province-Kunming Medical University [2008CD016, 2010CD156]
机构署名:
本校为第一且通讯机构
院系归属:
基础医学院
第一临床医学院
生物医学工程研究中心
摘要:
BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: BV-2 cells were pretreated with gastrodin (30, 40, and 60 microM) for 1 h and then stimulated with LPS (1 microg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-kappaB (NF-kappaB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-alpha, IL-1beta and NF-kappaB. LPS (1 microg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 microM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha) (and hence the activation of NF-kappaB) and of CREB, respectively. CONCLUSION AND IMPLICATIONS: This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-kappaB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.
参考文献:
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