Panax notoginseng saponins protects H9c2 cardiomyocytes against hypoxia/reoxygenation injury via activating the JAK2/STAT3 pathway

Panax notoginseng saponin (PNS) is isolated from Panax notoginseng, a traditional chinese herbal medicine with cardioprotective effects. Accumulating evidence has confirmed that the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway plays a vital role in mediating cardioprotection against ischemia/reperfusion (I/R) injury. Herein, the purpose of this study was to investigate the role of the JAK2/STAT3 pathway in the cardioprotective effects of PNS during hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. The results showed that PNS pretreatment significantly blocked H/R-induced down-regulation of cell viability and the up-regulation of LDH release in H9c2 cells. Meanwhile, PNS obviously reversed H/R-induced decrease in the ratio of p-JAK2/JAK2 and p-STAT3/STAT3, indicating that PNS activates the JAK2/STAT3 pathway. Subsequently, the results revealed that, JAK2 siRNA transfection reduced JAK2 miRNA and protein levels as well as p-STAT3/STAT3, and further remarkably abolished PNS-inhibited H/R-induced cytotoxicity and apoptosis as revealed by the decrease in cell viability and the increases in LDH release, apoptosis ratio, caspase-3 activity and Bax/Bcl-2 ratio. In addition, PNS reversed H/R-induced increase in ROS generation and MDA content, and decreased the SOD and GSH-PX activities, while these effects were blocked by JAK2 miRNA. These results suggest that PNS ameliorates H/R-induced apoptosis and oxidative stress by activating the JAK2/STAT3 pathway in H9c2 cardiomyocytes.