Astragaloside IV protects cardiomyocytes against hypoxia injury via HIF-1α and the JAK2/STAT3 pathway

Background: Hypoxia is an important cause of myocardial injury due to the heart's high susceptibility to hypoxia. Astragaloside IV (AS-IV) is the main component of Astragalus membranaceus and could exert cardiac protective role. Here, the effect of AS-IV on hypoxia-injured H9c2 cardiomyocytes was elucidated. Methods: First, H9c2 cells were exposed to hypoxia and/or AS-IV treatment. Cell apoptosis, death, and viability as well as hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression and apoptotic proteins were analyzed. Next, transfection of si-HIF-1 alpha into H9c2 cells was carried out to test whether upregulation and stabilization of HIF-1 alpha influences the effect of AS-IV on hypoxia-treated H9c2 cells. Furthermore, the regulatory role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling on HIF-1 alpha levels was examined. Results: Hypoxia suppressed viability and promoted the apoptosis and death of H9c2 cells. AS-IV eliminated hypoxia-induced H9c2 injury. Moreover, HIF-1 alpha signaling was further activated and stabilized by AS-IV in hypoxia-challenged H9c2 cells. Downregulation of HIF-1 alpha suppressed the function of AS-IV in hypoxia-challenged H9c2 cells. AS-IV promoted JAK2/STAT3 signaling in hypoxia-induced injury. The beneficial functions of AS-IV in hypoxia-exposed H9c2 cells were linked to HIF-1 alpha upregulation and JAK2/ STAT3 signaling activation. Conclusions: AS-IV relieved H9c2 cardiomyocyte injury after hypoxia, possibly by activating JAK2/ STAT3-mediated HIF-1 alpha signaling.

Automated summary

The study demonstrated that AS-IV alleviated hypoxia-induced injury in H9c2 cardiomyocytes by activating JAK2/STAT3-mediated HIF-1α signaling.