The Natural Flavone Acacetin Confers Significant Cardioprotection Against Ischemia/reperfusion Injury

Introduction:Cardiomyopathy and heart failure followed by myocardial ischemia/reperfusion injury(MI/RI)is a clinical problem,although the great effort has been making for preventing and/or protecting against the injury induced by myocardial reperfusion.Previous study showed that the natural flavone acacetin confers significant cardioprotection against ischemia/reperfusion injury through the anti-inflammatory,anti-oxidation,anti-apoptosis,etc.In this study,we investigate whether acacetin has protection against myocardial injury induced by reperfusionto explore the therapeutic potential of myocardial reperfusion injury.Methods:Myocardial ischemia/reperfusion model was established in anesthetized SD rats(n=80,body weight 250-300g)by opening chest and ligating the proximal left anterior descending coronary arteries(LADs)for 35 min followed by reperfusion.Drug administration was made by subcutaneous cervical injection.Animals were randomly divided into 4 groups:sham operation group,drug vehicle group,pre-ischemic drug group(Pre-Acacetin,acacetin injected before surgery 15 min),and post-ischemic drug group(Post-Acacetin,acacetin injected before reperfusion 15 min).Acacetin was administered(10 mg/kg,b.i.d.)for 7 days after the operation.Electrocardiogram was recorded to analyze cardiac electrical activity,echocardiography was used to assess cardiac function,and multiple biochemical and molecular biological approaches were employed to determine molecules involved in myocardial ischemia/reperfusion injury.Results:We found that that in animals with preischemic drug administration acacetin significantly reduced malignant arrhythmia incidence and duration.In animals with prereperfusion drug administration,acacetin,like preischemic drug administration,reduced reperfusion-induced arrhythmia score.Acacetin significantly improved myocardial function,decreased myocardial infarct size and fibrosis in either animals with preischemic administration or prereperfusion administration.Acacetin also reversed the plasma SOD redction,MDA increase,and proinflammatory factor IL-6 elevation.In addition,western blot analysis with myocardial tissues showed that acacetin descreased the pro-apoptotic protein Bax,reduced TLR-4 and type I collagen and enhanced antioxidation-related Nrf2,HO-land SOD1 in myocardial tissueConclusion:Our results demonstrate that pre-reperfusion administration of acacetin,like preischmic administration,significantly improves heart function and reduces myocardial infarct size and fibrosis induced by ischemia/reperfusion injury.The protective effects are involved in anti-inflammatory,antioxidant,anti-apoptosis,and anti-fibrosis,indicating that acacetin has therapeutic potential to prevent the maycardial injury induced by reperfusion.