Curculigo orchioides(CUR)and Epimedium(EPI)are traditional Chinese medicines with estrogen-like biological activity,called Xianmao and Xianlingpi(Er-xian)in Chinese.However,whether Er-xian exerts protective effects on myocardial ischemia-reperfusion injury(MIRI)is unknown.This study aimed to investigate the cardioprotective effects of Er-xian precondition-ing against MIRI and the underlying mechanisms.CUR or EPI was administered intragastrically to aged female rats as a monotherapy or combination therapy.2 weeks later,a rat MIRI model was established.Myocardial infarction size,myocardial morphology,cTnT,cell apoptosis rate,intracellular calcium concentration,mitochondrial permeability transition pore(MPTP)opening and reperfusion in-jury salvage kinase(RISK)signaling pathway molecules were observed after the surgery.To evaluate the mechanisms of Er-xian,es-trogen receptors antagonists ICI 182780 and G15 were used.In this study,Er-xian notably alleviated myocardial tissue damage,main-tained mitochondrial morphology,reduced infarct size and cardiac markers,and increased sera levels of E2.Moreover,Er-xian inhib-ited calcium overload and mPTP opening,and decreased cardiomyocyte apoptosis.We found that the dual therapy of CUR and EPI eli-cited more noticeable results than CUR or EPI monotherapy.The significant protective effects of Er-xian on ischemia-reperfusion myocardium were attributed to the up-regulation of AKT,ERK1/2 and GSK-3β phosphorylation levels.The cardioprotective effects of Er-xian were significantly reduced after estrogen receptor blockade,especially GPER30.These results indicate that Er-xian attenuates MIRI through RISK signaling pathway and estrogen receptors are the critical mediators.

QIANG Mingmin;HAO Jiping;LIU Huihui;YIN Jia;ZHANG Hui;YANG Jinxin;MENG Hudie;CHEN Yuqing;GAO Yuqin

College of Medicine,Yan'an University,Yan'an 716000,China;Department of Ultrasound Medicine,Ninth Hospital of Xi'an Affiliated to Xi'an Jiaotong University,Xi'an 710054,China;Department of Cardiology,Ninth Hospital of Xi'an Affiliated to Xi'an Jiaotong University,Xi'an 710054,China

中国天然药物

[1]QIANG Mingmin;HAO Jiping;LIU Huihui;YIN Jia;ZHANG Hui;YANG Jinxin;MENG Hudie;CHEN Yuqing;GAO Yuqin-.Er-xian ameliorates myocardial ischemia-reperfusion injury in rats through RISK pathway involving estrogen receptors)[J].中国天然药物,2022(12):902-913

Curculigo,orchioides,Xianmao,Xianlingpi,eli,GPER30

Er,xian,ameliorates,myocardial,ischemia,reperfusion,injury,rats,through,RISK,pathway,involving,estrogen,receptors,CUR,Epimedium,EPI,are,traditional,Chinese,medicines,like,biological,activity,called,However,whether,exerts,effects,MIRI,unknown,This,study,aimed,investigate,cardioprotective,precondition,against,underlying,mechanisms,was,administered,intragastrically,aged,female,monotherapy,combination,weeks,later,model,established,Myocardial,infarction,size,morphology,cTnT,apoptosis,intracellular,calcium,concentration,mitochondrial,permeability,transition,pore,MPTP,opening,salvage,kinase,signaling,molecules,were,observed,after,surgery,To,evaluate,antagonists,ICI,G15,used,In,this,notably,alleviated,tissue,damage,main,tained,reduced,cardiac,markers,increased,sera,levels,E2,Moreover,inhib,overload,mPTP,decreased,cardiomyocyte,We,found,that,dual,cited,more,noticeable,results,than,myocardium,attributed,up,regulation,AKT,ERK1,GSK,phosphorylation,significantly,blockade,especially,These,indicate,attenuates,critical,mediators

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