Antiapoptotic Effect of Novel Compound from Herba leonuri-Leonurine (SCM-198): A Mechanism Through Inhibition of Mitochondria Dysfunction in H9c2 Cells

摘要: Apoptosis of cardiomyocytes induced by oxidative stress play a critical role in cardiac dysfunction associated with ventricular remodeling and heart failure. We recently reported that leonurine attenuated hypoxia-induced cardiomyocyte damage. In this study, we investigated the mechanism (originally from Herba leonuri but synthesized it chemically, as also called SCM-198) protecting hydrogen peroxide (H2O2)-induced rat embryonic heart-derived H9c2 cells apoptosis. Exposing to H2O2 significantly decreased cell viability, was pretreatment for 4 h concentration-dependent manner. Meanwhile, found reduce intracellular reactive oxygen species (ROS) generation H2O2-stimulated cell. Moreover, stimulated accompanied apparent apoptotic characteristics, including fragmentation DNA, body formation, release cytochrome c, translocation Bax mitochondria, loss mitochondrial membrane potential (Δψm) activation caspase 3. Furthermore, rapid significant phosphorylation c-Jun-N-terminal kinase 1/2 (JNK1/2), which inhibited SP600125 (a JNK1/2 inhibitor). All these events were pretreatment. Taken together, results demonstrated could protect H2O2-induced apoptosis via modulation blocking JNK1/2.