Abstract
Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application.
Highlights
Ischemia-reperfusion (I/R) injury, a general healthy problem, is due to blood restoration after a critical period of coronary artery obstructions
It is widely accepted that oxidative stress, which is associated with increased formation of ROS, plays a major role in the pathogenesis of ischemia-reperfusion injury [1, 2]
H2O2, MDA content, and the formation of conjugated dienes in the heart were increased in ischemiareperfusion injury, while antioxidants such as superoxide dismutase (SOD) and catalase protected against these changes
Summary
Ischemia-reperfusion (I/R) injury, a general healthy problem, is due to blood restoration after a critical period of coronary artery obstructions. It associates with a series of clinical problems such as thrombolysis, angioplasty, and coronary bypass surgery [1, 2]. Apoptosis is a significant cellular mechanism responsible for ischemia-reperfusion injury in myocardium, and oxidative stress is a well-known factor promoting apoptosis [3, 4]. Reduction of apoptosis caused by oxidative stress could be an effective therapy for attenuation of ischemia-reperfusion injury. Caffeic acid derivatives occur as the major water-soluble components of Salvia miltiorrhiza. Altogether twenty-five caffeic acid derivatives have been isolated from S. miltiorrhiza
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