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Luteolin-7-diglucuronide attenuates isoproterenol-induced myocardial injury and fibrosis in mice

文献类型：期刊论文

作者Ning, Bing-Bing2; Zhang, Yong1; Wu, Dan-Dan2; Cui, Jin-Gang2; Liu, Li2; Wang, Pei-Wei2; Wang, Wen-Jian2; Zhu, Wei-Liang1; Chen, Yu2; Zhang, Teng2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2017-03
卷号38期号:3页码:331-341
关键词luteolin-7-diglucuronide ISO myocardial injury myocardial fibrosis NADPH oxidase collagen genes microRNAs TGF beta
ISSN号1671-4083
DOI10.1038/aps.2016.142
文献子类Article
英文摘要Myocardial injury and ensuing fibrotic alterations impair normal heart architecture and cause cardiac dysfunction. Oxidative stress has been recognized as a key player in the pathogenesis of cardiac injury and progression of cardiac dysfunction, and promoting fibrosis. In the current study we investigated whether luteolin-7-diglucuronide (L7DG), a naturally occurring antioxidant found in edible plants, could attenuate isoproterenol (ISO)-induced myocardial injury and fibrosis in mice and the underlying mechanisms. Myocardial injury and fibrosis were induced in mice via injection of ISO (5 mg . kg(-1) u d(-1), ip) for 5 or 10 d. Two treatment regimens (pretreatment and posttreatment) were employed to administer L7DG (5-40 mg . kg(-1) . d(-1), ip) into the mice. After the mice were euthanized, morphological examinations of heart sections revealed that both L7DG pretreatment and posttreatment regimens significantly attenuated ISOinduced myocardial injury and fibrosis. But the pretreatment regimen caused better protection against ISO-induced myocardial fibrosis than the posttreatment regimen. Furthermore, L7DG pretreatment blocked ISO-stimulated expression of the genes (Cyba, Cybb, Ncf1, Ncf4 and Rac2) encoding the enzymatic subunits of NADPH oxidase, which was the primary source of oxidant production in mammalian cells. Moreover, L7DG pretreatment significantly suppressed ISO-stimulated expression of collagen genes Col1a1, Col1a2, Col3a1, and Col12a1 and non-collagen extracellular matrix genes fibrillin-1, elastin, collagen triple helix repeat containing 1 and connective tissue growth factor. In addition, L7DG pretreatment almost reversed ISO-altered expression of microRNAs that were crosstalking with TGF beta-mediated fibrosis, including miR-29c-3p, miR-29c-5p, miR-30c-3p, miR-30c-5p and miR-21. The current study demonstrated for the first time that L7DG is pharmacologically effective in protecting the heart against developing ISO-induced injury and fibrosis, justifying further evaluation of L7DG as a cardioprotective agent to treat related cardiovascular diseases.
WOS关键词CARDIAC MAGNETIC-RESONANCE ; EXTRACELLULAR-MATRIX ; OXIDATIVE STRESS ; INFARCTION ; MICRORNAS ; BETA ; NECROSIS ; HEART ; CARDIOMYOPATHY ; PROLIFERATION
资助项目Program of Eastern Scholar at Shanghai Institutions of Higher Learning[00000000] ; Shu Guang Project - Shanghai Municipal Education Commission[13SG42] ; National Natural Science Foundation of China[81273960] ; National Natural Science Foundation of China[81473732]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5936498
WOS记录号WOS:000395792800004
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/272758]  
专题药物发现与设计中心
通讯作者Chen, Yu; Zhang, Teng
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Clin Res Inst Integrat Med, Shanghai 200437, Peoples R China;
推荐引用方式
GB/T 7714		 Ning, Bing-Bing,Zhang, Yong,Wu, Dan-Dan,et al. Luteolin-7-diglucuronide attenuates isoproterenol-induced myocardial injury and fibrosis in mice[J]. ACTA PHARMACOLOGICA SINICA,2017,38(3):331-341.
APA Ning, Bing-Bing.,Zhang, Yong.,Wu, Dan-Dan.,Cui, Jin-Gang.,Liu, Li.,...&Zhang, Teng.(2017).Luteolin-7-diglucuronide attenuates isoproterenol-induced myocardial injury and fibrosis in mice.ACTA PHARMACOLOGICA SINICA,38(3),331-341.
MLA Ning, Bing-Bing,et al."Luteolin-7-diglucuronide attenuates isoproterenol-induced myocardial injury and fibrosis in mice".ACTA PHARMACOLOGICA SINICA 38.3(2017):331-341.

入库方式： OAI收割

来源：上海药物研究所

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