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A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways
Cui G.1,2; Shan L.3; Hung M.1,2; Lei S.1,2; Choi I.1,2; Zhang Z.1,2,3; Yu P.3; Hoi P.1,2; Wang Y.3; Lee S.M.Y.1,2
2013
Source PublicationInternational Journal of Cardiology
ISSN1675273
Volume168Issue:2Pages:1349
Abstract

Background: Danshensu (3-(3,4-dihydroxyphenyl) lactic acid, DSS) is one of the most promising cardioprotective components in the root of Salvia miltiorrhiza but its poor chemical stability poses hurdles in its therapeutic development. It is therefore desirable to enhance the stability of DSS by chemical modification to improve its activities. In the present study, a novel DSS derivative named ADTM was synthesized and characterized for its cardioprotective properties. Methods: Oxidative stress was induced in H9c2 cardiomyoblast cells by tert-butylhydroperoxide (t-BHP) and the protective effects of ADTM were evaluated. For in vivo study, adult rats were treated with vehicle, DSS, ADTM or amlodipine (n=6-8/group) for 24 h before the induction of acute myocardial ischemia. At the end of each experiment, infarct sizewas measured. Underlying themechanisms of the cardioprotective effects of ADTMwere further investigated in H9c2 cells and rat myocardium by evaluating the effects of Nrf2 (NF-E2-related factor 2) and Akt/ PI3K pathways. Results: ADTMwas approximately 10 times more effective than DSS against t-BHP-induced cell injury in H9c2 cells. In rat myocardial ischemia model, ADTM treatment significantly alleviated myocardial infarction. Akt/PI3K and Nrf2 pathways were demonstrated to be involved in both in vitro and in vivo experiments. Conclusions: These results demonstrated that ADTM displayed much better cardioprotective effects than its parent compounds both in vitro and in vivo. This cardioprotection is mediated, at least in part, through Akt/PI3K and Nrf2 pathways. This novel compound represents a promising candidate for the treatment of cardiovascular diseases (CVDs), particularly myocardial infarction. © 2012 Elsevier Ireland Ltd. All rights reserved.

KeywordCardioprotection Danshensu Derivative Ischemia Nrf2 Oxidative Stress
DOI10.1016/j.ijcard.2012.12.012
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCardiovascular System & Cardiology
WOS SubjectCardiac & Cardiovascular Systems
WOS IDWOS:000325412800129
The Source to ArticleScopus
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Cited Times [WOS]:56   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorShan L.; Hoi P.; Lee S.M.Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine (University of Macau), Avenue Padre Tomás Pereira S.J., Macao SAR, China
2.Institute of Chinese Medical Sciences, University of Macau, Avenue Padre Tomás Pereira S.J., Taipa, Macao SAR, China
3.Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou, 510632, China
First Author AffilicationUniversity of Macau;  Institute of Chinese Medical Sciences
Corresponding Author AffilicationUniversity of Macau;  Institute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Cui G.,Shan L.,Hung M.,et al. A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways[J]. International Journal of Cardiology,2013,168(2):1349.
APA Cui G..,Shan L..,Hung M..,Lei S..,Choi I..,...&Lee S.M.Y..(2013).A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways.International Journal of Cardiology,168(2),1349.
MLA Cui G.,et al."A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways".International Journal of Cardiology 168.2(2013):1349.
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