Protective Effects of Pterostilbene Against Myocardial Ischemia/Reperfusion Injury in Rats
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ORIGINAL ARTICLE
Protective Effects of Pterostilbene Against Myocardial Ischemia/ Reperfusion Injury in Rats Miao Wu,1,2 Shijuan Lu,1 Jianghua Zhong,1 Kang Huang,1 and Saidan Zhang2,3
Abstract—Pterostilbene (PTB) has been suggested to protect against myocardial ischemia/reperfusion (MI/R) injury. Gas6/Axl signaling has been suggested to play an important role in cell survival. However, the interaction between PTB and Gas6/Axl signaling in MI/R remains unclear. This study aims to evaluate the role of Gas6/Axl signaling in the protective effects of PTB against MI/R injury. In experiment 1, the rats were subjected to 30 min of ischemia, followed by 3, 6, and 12 h of reperfusion, respectively. In experiment 2, the rats were administered intraperitoneally with PTB or vehicle and subjected to MI/R injury. The results suggested that the expression of Gas6 and Axl decreased significantly after MI/R injury. PTB treatment conferred a cardioprotective effect with an improved post-ischemic cardiac function, a reduced myocardial infarct size, and decreased lactate dehydrogenase and creatine kinase-MB in the serum, a decreased oxidative stress and inflammation, and a reduced number of apoptotic cardiomyocytes. Moreover, PTB treatment up-regulated the expression of Gas6, Axl, and Bcl-2 and down-regulated Bax expression. Our findings suggest that PTB treatment exerts cardioprotection against MI/R injury via attenuating inflammatory response, oxidative stress, and apoptosis and up-regulating the expression of Gas6 and Axl. The application of PTB may be a new strategy for the treatment of MI/R injury. KEY WORDS: pterostilbene; myocardial ischemia/reperfusion injury; Gas6/Axl signaling; oxidative stress; inflammation.
INTRODUCTION Myocardial ischemia/reperfusion (MI/R) injury is the primary cause of cardiac failure and has a morbidity and mortality worldwide [1, 2]. Accumulating evidence suggests that the oxidative stress induced by the overproduction of reactive oxygen species (ROS) during the acute reperfusion phase plays a pivotal role in the pathogenesis of MI/R injury [3, 4]. In addition, ROS induces 1
Department of Cardiology, Haikou People’s Hospital, Xiangya School of Medicine Affiliated Haikou Hospital, Central South University, Haikou, 570208, People’s Republic of China 2 Department of Cardiology, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China 3 To whom correspondence should be addressed at Department of Cardiology, Xiangya Hospital, Central South University, No.88 Xiangya Road, Changsha, 410078, People’s Republic of China. E-mail: [email protected]
inflammation, leading to severe myocardial injury [3, 5]. Therefore, diminishing ROS production is a novel target for attenuating MI/R injury. Pterostilbene (PTB, Fig. 1), a natural dimethylated analog of resveratrol from blueberries, has been reported to exert various pharmacological effects, such as anti-cancer, anti-inflammation, and anti-oxidant [6]. Due to methoxyl substitution-induced hyperlipophilicity, PTB may present high
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