title: Icaritin Attenuates Myocardial Ischemia and Reperfusion Injury Via Anti-Inflammatory and Anti-Oxidative Stress Effects in Rats.
abstract: Icaritin (ICT) is a traditional Chinese medicinal herb proved to be neuroprotective and exerts promoting effects on cardiac differentiation. However, its role in cardioprotection against myocardial ischemia/reperfusion (MI/R) injury remains largely unknown. This study aimed to investigate the effects of ICT treatment on MI/R injury and the underlying mechanisms. Rats were subjected to 30 min of myocardial ischemic insult followed by 3 h of reperfusion. ICT (3, 10, and 30 mg/kg) was administered intraperitoneally 10 min before reperfusion. ICT treatment at the dose of 10 and 30 mg/kg improved cardiac function and limited infarct size following MI/R. Meanwhile, ICT reduced plasma creatine kinase (CK), lactate dehydrogenase (LDH) activities and cardiomyocyte apoptosis in I/R heart tissue. Moreover, ICT treatment not only inhibited the pro-inflammatory cytokine TNF-α production and increased the anti-inflammatory cytokine IL-10 level in myocardium but also reduced the increase in the generation of superoxide content and malondialdehyde (MDA) formation and simultaneously increased the anti-oxidant capability in I/R hearts. Furthermore, ICT treatment increased Akt phosphorylation and inhibited PTEN expression in I/R hearts. PI3K inhibitor wortmannin inhibited ICT-enhanced Akt phosphorylation, and blunted ICT-mediated anti-oxidative and anti-inflammatory effects and cardioprotection. Our study indicated for the first time that ICT reduces inflammation and oxidative stress and protects against MI/R injury in rats, which might be via a PI3K-Akt-dependent mechanism.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.|Department of Cardiothoracic Surgery, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors.forename: Baichun
authors.initials: B
authors.lastname: Xing
authors.affiliation: Department of Anesthesiology, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, Peace Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors.forename: Jialun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; C499403:icaritin
keywords: Akt; Icaritin; Inflammation; Myocardial Ischemia/Reperfusion; Oxidative Stress