Angelica Sinensis Polysaccharide Protects Against Myocardial Ischemia/Reperfusion Injury Via Oip5-as1 Mediated SIRT1-AMPK-PGC1? Pathway

Background: Acute myocardial infarction(AMI)is a leading cause of morbidity and mortality worldwide.Timely restoration of myocardial blood flow is a cornerstone of the treatment of AMI.However,reperfusion itself can cause myocardial damage,namely myocardial ischemia/reperfusion(MI/R)injury.Therefore,it is clinically important to find an approach to protect against MI/R injury following timely and complete reperfusion.Both experimental and clinical studies have highlighted that herbal medicines can reduce ischemic injury and improve cardiac function after AMI.Angelica sinensis,a geoherb in Gansu,has been used in treating cardiovascular diseases.However,it remains not completely understood that the biological activities and the molecular mechanisms of action underlying cardioprotective effects of Angelica sinensis.Objective: To study the protective effect and molecular mechanism of active components of Angelica sinensis on MI/R injury.Methods: 1.To screen major component of Angelica Sinensis on cardioprotective role and its potential pathway using network pharmacology analysis(Part 1).2.By means of in vitro,in vivo,and molecular biology experiments,we examined the effect of Angelica sinensis polysaccharide(ASP),the active constituent of Angelica sinensis by network pharmacology on protecting against MI/R injury.The role of ASP on SIRT1-AMPK-PGC1? signaling pathway was also analyzed(Part 2).3.By means of experiments,we studied the action of ASP on OPA-interacting protein 5 antisense transcript 1(Oip5-as1)expression and the detailed molecular mechanism by which Oip5-as1 regulates SIRT1-AMPK-PGC1? pathway(Part 3).Results: 1.By using network pharmacology,we found that ASP may be an important active ingredient for Angelica sinensis exerting cardioprotective effects,and SIRT1-AMPK-PGC1? pathway may be its potential mechanism.2.ASP ameliorates the mitochondrial dysfunction,oxidative injury,and apoptosis through activating SIRT1-AMPK-PGC1? pathway in the in vitro experiments.3.The in vitro experiments showed that ASP promotes Oip5-as1 expression.Oip5-as1 acts as a ce RNA to regulate SIRT1 m RNA expression,thereby activating the SIRT1-AMPK-PGC1? signaling pathway.4.The in vivo experiments found that ASP treatment ameliorates MI/R injury.ASP therapy promotes the expression level of Oip5-as1 and upregulates SIRT1-AMPK-PGC1? signaling pathway.Conclusions: 1.The network pharmacology is a feasible method to screen active ingredients of Angelica sinensis and its mechanism of action on cardioprotective role.2.ASP upregulates the level of Oip5-as1 to activate the SIRT1-AMPK-PGC1? signaling pathway.ASP reduces oxidative stress,inhibits the mitochondrial apoptosis pathway,and ultimately reduces cell apoptosis and exerts protective effect against MI/R injury.