Scutellarin protects cardiomyocyte ischemia-reperfusion injury by reducing apoptosis and oxidative stress.

OBJECTIVE

Ischemic heart disease is a leading cause of death and disability worldwide. Despite recent advances, there is no effective therapy for preventing myocardial ischemia-reperfusion (I/R) injury. In this study, we aimed to examine the therapeutic effect of scutellarin, a flavone isolated from the traditional Chinese medicine Scutellaria barbata and Erigeron breviscapus, on cardiomyocyte I/R injury.

METHODS

Neonatal rat cardiomyoblast cells H9C2 were used to study the role of scutellarin in cardiomyocyte injury. I/R injury was induced by 2h of hypoxia plus glucose and serum deprivation, followed by 6-hour recovery. Cardiomyocyte damage was evaluated by the release of pro-inflammatory cytokines and creatine kinase (CK), apoptosis, and cell proliferation. Oxidative responses were assessed by reactive oxygen species (ROS) production, MDA generation, SOD expression, and mitochondrial membrane potential detection. Activation of JAK2/STAT3 signaling and expression of pro- or anti-survival molecules were detected by Western blot.

RESULTS

I/R injury increased the release of CK as well as pro-inflammatory cytokines TNFα, IL-1β, IL-6, and IL-8 from cardiomyocytes. ROS, MDA, and apoptosis were enhanced in cardiomyocytes underwent I/R injury, while cell proliferation, mitochondrial membrane potential, SOD expression were reduced. Scutellarin treatment dose-dependently suppressed I/R injury-induced pro-inflammatory cytokine and CK release, oxidative response, loss of mitochondrial membrane potential, and enhanced cell proliferation and anti-oxidant SOD expression. Further analysis suggests scutellarin promotes JAK/STAT3 activation and expression of pro-survival proteins Bcl2, VEGF, MMP2, and MMP9. Pro-apoptotic molecules Bax and caspase-3 were suppressed by scutellarin.

CONCLUSIONS

We identified a previously unrecognized pathway by which scutellarin protects myocardial I/R injury. Scutellarin modulates I/R injury-induced oxidative stress and apoptosis probably by enhancing JAK2/STAT3 pro-survival signaling.