Rhein Activates Janus Protein Tyrosine Kinase2/Signal Transducer and Transcription Activation Factor3 Reduces Mitochondrial Oxidative Damage Caused by Myocardial Ischemia/Reperfusion Injury

Background: Rhein is a kind of lipophilic anthraquinone widely existing in herbal medicine. Here we aim to investigate whether Rhein can reduce the degree of myocardial ischemia/reperfusion injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of Rhein in protecting myocardial cells. Methods: The anti-oxidation and anti-apoptosis effects of Rhein were studied by using the primary myocardial cells of ischemia/reperfusion rat as the model of myocardial injury. Cell viability was detected by MTT, The level of LDH and CK-MB released by cardiomyocytes was measured by Colorimetric assay. The ROS was observed under microscope and the level of catalase and glutathione peroxidase were detected by enzymatic methods. The JAK2/STAT3 signaling pathway mediated by Rhein was observed by Western blot. Results: Compared with that of the SIR group, cell viability in the SIR and Rhein co-treatment groups increased significantly (P < 0.001), the release of LDH and CK-MB decreased, the positive rate of ROS in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, Rhein can activate JAK2/STAT3 signaling pathway. JAK2 siRNA can inhibit the JAK2/STAT3 signaling mediated by Rhein. The addition of Rhein can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the MDA, which indicates that the oxidative damage of mitochondria induced by Rhein was significantly weakened. The mitochondrial functional changes induced by Rhein can be reversed by JAK2 siRNA. Conclusion: Our study shows that Rhein can reduce ROS in cardiomyocytes by JAK2/STAT3 signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SIR.