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The histone deacetylase, sirtuin\u20101, plays a protective role in ischaemia\/reperfusion (I\/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I\/R injury and to elucidate the potential involvement of sirtuin\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>I\/R injury was simulated <jats:italic>in vivo<\/jats:italic> (mouse hearts), <jats:italic>ex vivo<\/jats:italic> (isolated rat hearts) and <jats:italic>in vitro<\/jats:italic> (neonatal rat cardiomyocytes and H9c2 cells). Prior to I\/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin\u20101 (sirtinol and SIRT1 siRNA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:italic>In vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, icariin given before I\/R significantly improved post\u2010I\/R heart contraction and limited the infarct size and leakage of creatine kinase\u2010MB and LDH from the damaged myocardium. Icariin also attenuated I\/R\u2010induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn\u2010superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin\u20101 was significantly up\u2010regulated in hearts treated with icariin, whereas Ac\u2010FOXO1 was simultaneously down\u2010regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin\u2010induced cardioprotection or disrupted icariin\u2010mediated mitochondrial homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Pretreatment with icariin protected cardiomyocytes from I\/R\u2010induced oxidative stress through activation of sirtuin\u20101 \/FOXO1 signalling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14457","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T03:54:18Z","timestamp":1532663658000},"page":"4137-4153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Icariin protects cardiomyocytes against ischaemia\/reperfusion injury by attenuating sirtuin 1\u2010dependent mitochondrial oxidative damage"],"prefix":"10.1111","volume":"175","author":[{"given":"Bing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Geriatrics 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