Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction

Leonurine an alkaloid typically found in Herba leonuri is known to have both antioxidant and cardioprotective properties In the present study we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress Myocardial ischemia was induced by ligating the left anterior descending coronary artery Rats were divided into sham myocardial ischemia + saline and myocardial ischemia + leonurine (15 mg/kg/day) Cardiac function was recorded by catheterization Apoptosis-related factor vascular endothelial growth factor (VEGF) survivin Bcl-2 and Bax and pro-survival signaling pathways Akt hypoxia inducible factor (HIF) 1 alpha were measured by Western blotting or RT-PCR Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the Increased + dP/dt Interestingly leonurine increased the phosphorylation of Akt the protein and gene expression of Bcl-2 but it reduced the protein and gene expression of Bax in vivo Meanwhile leonurine significantly Increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro which was abolished by a phosphoinositide 3 kinase (PI3K) inhibitor LY294002 Furthermore leonurine not only increased the expression of HIF 1 alpha but also the expression of survivin and VEGF The results of present study demonstrated for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway Angiogenic mechanisms may be partially responsible for such an effect which needs to be studied further (C) 2010 Elsevier B V All nghts reserved