ABSTRACT
Cardiomyocyte apoptosis is closely associated with the pathogenesis of heart failure. Jujuboside A (JUA) is a type of saponin isolated from the seeds of Zizyphus jujuba. In traditional Chinese medicine, it is believed that JUA possesses multiple biological effects, including antianxiety, antioxidant and antiinflammatory activities. The present study aimed to evaluate the effects of JUA on norepinephrine (NE)induced apoptosis of H9c2 cells and to investigate its underlying mechanisms. Rat H9c2 cardiomyocytes were pretreated with JUA and were then exposed to NE as an in vitro model of myocardial apoptosis. A cell viability assay, scanning electron microscopy, transmission electron microscopy, flow cytometry assay, acridine orange/ethidium bromide staining, reverse transcriptionquantitative polymerase chain reaction and western blotting, all revealed that NE induced H9c2 cell apoptosis. The results demonstrated that NE inhibited cell viability, and enhanced cell damage and apoptosis of H9c2 cells. Conversely, pretreatment with JUA was able to reverse NEinduced decreased cell viability and increased apoptosis. Furthermore, JUA suppressed upregulation of the Bcell lymphoma 2 (Bcl2)associated X protein/Bcl2 ratio, and inhibited the increased protein expression levels of cleaved caspase3 and cleaved caspase9 following NE exposure. However, the protein expression levels of cleaved caspase12 and cleaved caspase8 were not significantly altered following exposure to NE or JUA pretreatment. In addition, in JUApretreated cells, the protein expression levels of phosphorylated (p)p38 and pcJun Nterminal kinase were downregulated compared with in NEtreated cells. Furthermore, JUA regulated the activation of extracellular signalregulated kinase (ERK) in NEtreated cells and significantly increased the expression levels of pAKT. Taken together, these data suggested that JUA may protect against NEinduced apoptosis of cardiomyocytes via modulation of the mitogenactivated protein kinase and AKT signaling pathways. Therefore, JUA may be considered a potential therapeutic strategy for the treatment of heart disease.