Danshensu, as the effective component of Salvia miltiorrhiza (Danshen), has been widely used in clinic for treatment of
cardiovascular diseases in China. In the present study, we aimed to confirm the cardioprotective effect of
Danshensu from
myocardial ischemia/reperfusion (MI/R) injury in vivo, and investigate the potential molecular mechanisms against simulated
ischemia/reperfusion (SI/R) induced cardiomyocytes apoptosis in vitro. The rat model of MI/R injury was induced by a transient vessel occlusion for 30 min and reperfusion for 3h,
Danshensu significantly reduced myocardium
infarct size and the production of
creatine kinase-MB (CK-MB), cardiac
troponin (cTnI) in serum. In vitro experiment, H9c2 cardiomyocytes were incubated with vehicle or ischemic
buffer during
hypoxia, and then it was reoxygenated with or without
Danshensu.
Danshensu markedly improved cell viability and decreased
lactate dehydrogenase (LDH) release. We confirmed anti-apoptotic effect of
Danshensu both by flow-cytometric analysis and
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and this effect was associated with the increase of Bcl-2/Bax ratio and the decrease of active
caspase-3 expression. Western blot analysis also showed that
Danshensu increased phosphorylation of Akt and extracellular signal-related
kinase 1/2 (ERK1/2) in H9c2 cells, and the protective effects of
Danshensu were partially inhibited by
phosphatidylinositol 3'-kinase (PI3K) specific inhibitor
wortmannin or ERK specific inhibitor
U0126. Our results suggested that
Danshensu could provide significant cardioprotection against MI/R injury, and the potential mechanisms might to suppression of cardiomyocytes apoptosis through activating the PI3K/Akt and ERK1/2 signaling pathways.