Affiliation:
1. Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
2. School of Pharmacy, Fudan University, Shanghai 201203, China
3. Department of Clinical Diagnostics, Hebei Medical University, Shijiazhuang 050017, China
Abstract
Myocardial ischemia-reperfusion (I/R), an important complication of reperfusion therapy for myocardial infarction, is characterized by hyperactive oxidative stress and inflammatory response. Leonurine (4-guanidino-n-butyl syringate, SCM-198), an alkaloid extracted from Herbaleonuri, was previously found to be highly cardioprotective both in vitro and in vivo. Our current study aimed to investigate the effect of SCM-198 preconditioning on myocardial I/R injury in vitro and in vivo, respectively, as well as to decipher the mechanism involved. Rats were pretreated with SCM-198 before subjected to 45 min of myocardial ischemia, which was followed by 24 h of reperfusion. Primary neonatal rat cardiac ventricular myocytes (NRCMs) were exposed to hypoxia (95% N2 + 5% CO2) for 12 h, and then to 12 h reoxygenation so as to mimic I/R. The enzymatic measurements demonstrated that SCM-198 reduced the release of infarction-related enzymes, and the hemodynamic and echocardiography measurements showed that SCM-198 restored cardiac functions, which suggested that SCM-198 could significantly reduce infarct size, maintaining cardiomyocyte morphology, and that SCM-198 pretreatment could significantly reduce cardiomyocytes apoptosis. Moreover, we demonstrated that SCM-198 could exert a cardioprotective effect by reducing reactive oxygen species (ROS) level and Akt phosphorylation while reducing the phosphorylation of p38 and JNK. In addition, the upregulation of p-Akt, Bcl-2/Bax induced by SCM-198 treatment were blocked by PI3K inhibitor LY294002, and the total protein level of Akt was not affected by SCM-198 pretreatment. Our experimental results indicated that SCM-198 could have a cardioprotective effect on I/R injury, which confirmed the utility of SCM-198 preconditioning as a strategy to prevent I/R injury.
Funder
Natural Science Foundation of China
Research Grant for Health Science and Technology of Shanghai Municipal Commission of Health Committee
Science and Technology Development Fund Of Shanghai Pudong New Area
Key Discipline Construction Project of Pudong Health Bureau of Shanghai : Clinical Pharmacy
Fudan Zhangjiang Clinical Medicine Innovation
Clinical Pharmacy Key Specialized subject Construction Project of Pudong Hospital affiliated to Fudan University
Shanghai Medical Institution Clinical Pharmacy Key Specialized Subject Construction Project
Subject
General Biochemistry, Genetics and Molecular Biology