Abstract
Oxidative stress induced by overproduction of reactive oxygen species (ROS) plays an important role in hypoxia/reoxygenation (H/R) injury. In the present study, effects of salvianolic acid A (1) on heart H/R injury through its antioxidant activity were examined, using a molecule-based ROS scavenging system and cardiomyocyte model of H/R injury, as well as isolated rat heart model. As a result, 1 showed a potent antioxidant activity, scavenging all of the tested ROS and DPPH (2,2-diphenyl-1-picrylhydrazyl). The antioxidant effect of 1 was also observed in cardiomyocytes exposed to H/R. Compound 1 remarkably decreased dihydroethidium and dichlorofluorescein fluorescence and increased cell viability and mitochondrial membrane potential, ΔΨm, when compared to the H/R group. In isolated rat hearts exposed to H/R, 1 markedly increased the coronary flow, the peak of pressure development and the valley of pressure development, and significantly reduced the left ventricular end diastolic pressure when compared to the H/R group. These results suggested that 1 had significant protective effects against H/R-induced myocardial injury through its antioxidant activity.
Acknowledgements
This research was supported by grants from the National Natural Sciences Foundation of China (NSFC) (Grant Numbers 30873063; 30873455), the National 973 Fundamental Project of China (Grant Number 2009CB523004), Natural Sciences Foundation of Beijing (Grant Number 7092068) and the Key Project of Youth Foundation of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Grant Number 2006QZH01). We are indebted to the grant from the National S&T Major Special Project on Major New Drug Innovation (Item Numbers: 2008ZX09401-004, 2009ZX09301-003, 2009ZX09303-003, 2009ZX09103-034).
Notes
† These two authors contributed equally to this work.
† These two authors contributed equally to this work.