Protective Role Of Silibinin Against Myocardial Ischemia/Reperfusion Injury-Induced Cardiac Dysfunction

Silibinin is a traditional medicine and utilized for liver protection with antioxidant, anti-inflammation and anti-apoptosis properties. However, its role in myocardial I/R injury and the mechanism involved is currently unknown. In the present study, Silibinin treatment improves cardiac function and limits infarct size, and subsequently inhibits fibrotic remodeling in mice with myocardial I/R injury. Mechanistically, silibinin reduces cardiomyocytes apoptosis, attenuates mitochondrial impairment and endoplasmic reticulum (ER) stress, alleviates ROS generation, neutrophil infiltration and cytokines release. Consistently, silibinin prevents H9C2 cells from hypoxia/reperfusion-induced cell death, oxidative stress and inflammation in vitro. Furthermore, H9C2 cells treated with silibinin blocks NF-kappa B signaling activation by inhibiting IKK alpha phosphorylation, I kappa B alpha degradation and p65 NF-kappa B nuclear translocation during hypoxia/ reperfusion. In addition, silibinin plus BAY 11-7082 (a selected NF-kappa B inhibitor) do not provide incremental benefits in improving myocytes apoptosis, oxidative stress and inflammation in comparison with NF-kappa B signaling inhibition only. Thus, silibinin-mediated cardioprotection in myocardial I/R injury is associated with decreased apoptosis, oxidative stress and inflammatory response through deactivation of NF-kappa B pathway.