Danshensu protects isolated heart against ischemia reperfusion injury through activation of Akt/ERK1/2/Nrf2 signaling

Danshen has been widely used in the treatment of cardiovascular diseases while Danshensu [3(3,4dihydroxyphenyl) 2 hydroxy propanoic acid, DSS], a major water-soluble component of Danshen has also been explored as an important compound in Danshen. In the present study, DSS was tested in isolated rat hearts of ischemia reperfusion (I/R) model to investigate its cardioprotective activity and explore the potential molecular mechanism against oxidative stress. The isolated rat hearts were used to perform global ischemia for 30 min, followed by 30 min reperfusion. DSS significantly decreased the level of the marker enzymes (creatine kinase and lactate dehydrogenase) from the coronary effluents and myocardial infarction size. This could markedly contribute to the recovery of cardiac function after I/R injury. DSS also had ROS scavenging activity and boosted endogenous antioxidants such as SOD, CAT, MDA, GSH-PX and HO-1 activities by activating nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway which was mediated by Akt and ERK1/2 in western blot analysis. Our results demonstrated a cardioprotective effect of DSS on isolated heart against oxidative stress during I/R injury. This mechanism might be related to the enhancement of antioxidant defense system by activating Akt/ERK1/2/Nrf2 signaling pathways. This work could provide experimental evidence in treating cardiovascular disease by the use of traditional Chinese medicine particularly in myocardial ischemia reperfusion injury.