Abstract
Inonotus obliquus (IO) is an edible fungus that exerts various biological functions, including anti-inflammatory, antitumor and immunomodulatory effects. The present study was designed to investigate the role of IO extract (IOE) in myocardial ischemia/reperfusion (MI/R) and determine the exact molecular mechanisms. The left anterior descending coronary artery was ligated to establish the MI/R injury model in rats. IOE exhibited a novel cardioprotective effect, as shown by improvement in cardiac function and decrease in infarct size. Pretreatment with IOE activated antioxidant enzymes in cardiomyocytes, including glutathione peroxidase, superoxide dismutase and catalase. IOE pretreatment also induced the upregulation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and downregulation of glucose-regulated protein 78, phosphorylated (p-) protein kinase R-like endoplasmic reticulum kinase, p-eukaryotic translation initiation factor 2 subunit α, C/EBP homologous protein and caspase-12. Furthermore, IOE alleviated endoplasmic reticulum (ER) stress-induced apoptosis in cardiomyocytes by decreasing the mRNA levels of caspase-12. IOE inhibited apoptosis induced by overexpression of pro-caspase-9 and pro-caspase-3. In summary, IOE pretreatment protects the heart against MI/R injury through attenuating oxidative damage and suppressing ER stress-induced apoptosis, which may be primarily due to SIRT1 activation.
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