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Open Access Highly Accessed Research article

Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

Baohong Jiang1, Jing Chen1, Lingling Xu1, Zhenting Gao2, Yanping Deng1, Yanhui Wang13, Feng Xu3, Xu Shen1* and De-an Guo1*

Author Affiliations

1 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

2 School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

3 Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China

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BMC Pharmacology 2010, 10:10  doi:10.1186/1471-2210-10-10

Published: 25 August 2010

Abstract

Background

Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9).

Results

Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis.

Conclusions

As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted.