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)-1α 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-1α 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.