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-κB signaling activation by inhibiting IKKα phosphorylation, IκBα degradation and p65 NF-κB nuclear translocation during hypoxia/ reperfusion. In addition, silibinin plus BAY 11-7082 (a selected NF-κB inhibitor) do not provide incremental benefits in improving myocytes apoptosis, oxidative stress and inflammation in comparison with NF-κB 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-κB pathway.
Keywords: Apoptosis; Inflammation; Myocardial I/R injury; NF-κB; Oxidative stress; Silibinin.
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