RGD Reference Report - A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways. - Rat Genome Database

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A novel Danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways.

Authors: Cui, G  Shan, L  Hung, M  Lei, S  Choi, I  Zhang, Z  Yu, P  Hoi, P  Wang, Y  Lee, SM 
Citation: Cui G, etal., Int J Cardiol. 2013 Sep 30;168(2):1349-59. doi: 10.1016/j.ijcard.2012.12.012. Epub 2013 Jan 4.
RGD ID: 10412734
Pubmed: PMID:23290949   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ijcard.2012.12.012   (Journal Full-text)

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 24h before the induction of acute myocardial ischemia. At the end of each experiment, infarct size was measured. Underlying the mechanisms of the cardioprotective effects of ADTM were further investigated in H9c2 cells and rat myocardium by evaluating the effects of Nrf2 (NF-E2-related factor 2) and Akt/PI3K pathways. RESULTS: ADTM was 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocardial infarction treatmentISONfe2l2 (Rattus norvegicus)10412734; 10412734 RGD 
myocardial infarction treatmentIDA 10412734 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfe2l2  (NFE2 like bZIP transcription factor 2)

Genes (Mus musculus)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)

Genes (Homo sapiens)
NFE2L2  (NFE2 like bZIP transcription factor 2)


Additional Information