Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice
文献类型:期刊论文
作者 | Zhang, Tingting1,2,3; Xu, Jinghua2; Li, Defang1; Chen, Jing1![]() ![]() |
刊名 | PHYTOMEDICINE
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出版日期 | 2014-09 |
卷号 | 21期号:10页码:1137-1145 |
关键词 | Salvianolic acid A Salvia miltiorrhiza Aortic aneurysm Matrix metalloproteinase Doxycycline Danshen |
ISSN号 | 0944-7113 |
DOI | 10.1016/j.phymed.2014.05.003 |
文献子类 | Article |
英文摘要 | Aortic aneurysm (AA) is a life-threatening vascular disease in defect of effective pharmaceutical therapy. Matrix metalloproteinase-9 (MMP-9) is implicated in the development of chronic vascular diseases including aneurysm, but the effective MMP-9 inhibitors are far from development. To develop new candidate for AA therapy, we evaluated the efficiency of salvianolic acid A (SalA), a novel MMP-9 inhibitor, on AA progression in a mouse model and characterized the mechanism of action. SalA is a water soluble compound of the herbal drug Rhizoma Salviae miltiorrhizae (Danshen) which in China is widely used for the treatment of hypertension, coronary artery diseases and myocardial infarction. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. SalA showed selectivity on gelatinase (MMP-2 and MMP-9) than on collagenase (MMP-8 and MMP-13) in vitro, and specificity on MMP-9 than MMP-2 in vivo. Aortic aneurysm was induced by angiotension II (Ana) in apolipoprotein E-deficient (ApoE(-/-)) mice. Aortic structure was evaluated by hematoxylin and eosin, picrosirius red, orein stain. Macrophage infiltration was detected by immunohistochemistry in vivo and transwell in vitro. Comparing with doxycycline (Dox), a well-known MMPs inhibitor, SalA showed similar efficiency against AA progression. SalA significantly decreased aortic diameter and aneurysm severity, ameliorated integrity of vascular structure, inhibited elastin fragmentation and macrophage infiltration. Furthermore, SalA showed greater safety than Dox based on hepatotoxicity evaluation. Our results demonstrated that SalA held great potential for AA therapy. (C) 2014 Elsevier GmbH. All rights reserved. |
WOS关键词 | MATRIX METALLOPROTEINASES ; DOXYCYCLINE THERAPY ; DISEASE ; REPAIR ; LEVEL |
资助项目 | National Science & Technology Major Project for "Key New Drug Creation and Manufacturing Program"[2013ZX09103002-024] ; National Science & Technology Major Project for "Key New Drug Creation and Manufacturing Program"[2011ZX09307-002-03] ; National Natural Science Foundation of China Grants[81173587] ; Shanghai Science and Technology Development Foundation of Experimental Animal Research Project[12140902400] ; Global Research Network for Medicinal Plants (GRNMP) and King Saud University[00000000] ; National High Technology Research and Development Program ("863" Program) of China[SS2013AA09002] ; Twelfth Five-Year National Science & Technology Support Program[2012BAI29B06] |
WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
语种 | 英语 |
WOS记录号 | WOS:000340336700002 |
出版者 | ELSEVIER GMBH, URBAN & FISCHER VERLAG |
源URL | [http://119.78.100.183/handle/2S10ELR8/276933] ![]() |
专题 | 上海中药现代化研究中心 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 |
通讯作者 | Jiang, Baohong |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.E China Univ Sci & Technol, Shanghai 200237, Peoples R China; 5.Hong Kong Baptist Univ, Sch Chinese Med, Inst Adv Translat Med Bone & Joint Dis, Hong Kong, Hong Kong, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Tingting,Xu, Jinghua,Li, Defang,et al. Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice[J]. PHYTOMEDICINE,2014,21(10):1137-1145. |
APA | Zhang, Tingting.,Xu, Jinghua.,Li, Defang.,Chen, Jing.,Shen, Xu.,...&Guo, Den.(2014).Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice.PHYTOMEDICINE,21(10),1137-1145. |
MLA | Zhang, Tingting,et al."Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice".PHYTOMEDICINE 21.10(2014):1137-1145. |
入库方式: OAI收割
来源:上海药物研究所
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