中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation

文献类型:期刊论文

作者Wu, Lei2,4; Wang, Hong-min1,3,4; Li, Jin-long1,3,4; Feng, Hong-xuan2,4; Zhao, Wei-min1,3; Zhang, Hai-yan2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2017-04
卷号38期号:4页码:459-468
关键词cerebral ischemia rosmarinic acid n-butyl ester SH-SY5Y neuroblastoma cells apoptosis death-associated protein kinase p53 microglia inflammation
ISSN号1671-4083
DOI10.1038/aps.2016.156
文献子类Article
英文摘要The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 mu mol/L) dose-dependently attenuated OGD-or H2O2-induced reduction of the viability of SH-SY5Y neuroblastoma cells. RABE pretreatment concurrently reduced the apoptotic cell rate, down-regulated the expression of the pro-apoptotic proteins Bax and p53, and up-regulated the expression of the anti-apoptotic protein phosphorylated death-associated protein kinase (DAPK). Furthermore, pretreatment with RABE (3 mu mol/L) markedly inhibited lipopolysaccharide (LPS)-induced increases in the release of TNF-alpha, IL-1 beta, NO and PGE2, and the expression levels of iNOS, and COX-2 in cultured rat microglial cells. In conclusion, these results reveal for the first time the potential anti-ischemic effects of RABE on neuronal and glial cells and elucidate the molecular mechanisms involved in its dual beneficial profiles in vitro. RABE may be a promising drug lead/candidate for the treatment of ischemic stroke.
WOS关键词ACUTE ISCHEMIC-STROKE ; TISSUE-PLASMINOGEN ACTIVATOR ; BRAIN ISCHEMIA ; NITRIC-OXIDE ; DEATH ; PATHWAY ; NEUROTOXICITY ; ASSOCIATION ; APOPTOSIS ; DISEASE
资助项目National Natural Science Foundation of China[81522045] ; National Natural Science Foundation of China[81473113] ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China[SIMM1601KF-03]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5953656
WOS记录号WOS:000399192700002
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/272725]  
专题天然药物化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药理学第二研究室
通讯作者Zhao, Wei-min; Zhang, Hai-yan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Nat Prod Chem, Shanghai 201203, Peoples R China;
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Wu, Lei,Wang, Hong-min,Li, Jin-long,et al. Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation[J]. ACTA PHARMACOLOGICA SINICA,2017,38(4):459-468.
APA Wu, Lei,Wang, Hong-min,Li, Jin-long,Feng, Hong-xuan,Zhao, Wei-min,&Zhang, Hai-yan.(2017).Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation.ACTA PHARMACOLOGICA SINICA,38(4),459-468.
MLA Wu, Lei,et al."Dual anti-ischemic effects of rosmarinic acid n-butyl ester via alleviation of DAPK-p53-mediated neuronal damage and microglial inflammation".ACTA PHARMACOLOGICA SINICA 38.4(2017):459-468.

入库方式: OAI收割

来源:上海药物研究所

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