Network pharmacology and experimental investigation of the mechanism underlying the cardiac protection effects of Shexiang Baoxin Pill in myocardial ischemia/reperfusion injury
JIA Yun-xi
LIN Yu
WANG Hui
ZHANG Feng-jiao
ZHANG Bo-ya
JIN Zhe
SONG Yu
LI Yong-jian
Abstract：Objective Myocardial ischemia-reperfusion injury(MIRI)is a significant complication of reperfusion therapy and remains a major clinical challenge worldwide.Shexiang Baoxin Pill(SXBX),a traditional Chinese medicine,has shown promising potential in the treatment of cardiovascular diseases.However,its precise mechanisms in alleviating MIRI remain unclear.The aim of this study was to investigate the pharmacological effects of SXBX on MIRI.Methods Seventy-two clean-grade healthy male C57BL/6J mice,aged 6-8 weeks and weighing 20-25 g,were selected.They were randomly divided into three groups(n=24)using a random number table:the sham operation group(Sham group),the myocardial ischemia-reperfusion group(MIRI group),and the myocardial ischemia-reperfusion+Shexiang Baoxin Pill group(MIRI+SXBX group).The MIRI model was established by ligation and reperfusion of the left anterior descending coronary artery.Mice were administered SXBX(20 mg/kg)for 10 consecutive days before and after surgery.Pathological changes,cardiac function,and autophagy markers were evaluated through histopathology,echocardiography,and Western blotting.Network pharmacology was utilized to identify potential molecular targets and signaling pathways of SXBX,and the findings were validated through pathway enrichment analyses and protein expression studies.Results SXBX treatment alleviated myocardial fiber damage,reduced serum levels of myocardial injury markers,and improved cardiac function,as evidenced by increased LVEF and LVFS.Moreover,SXBX inhibited myocardial autophagy by upregulating P62 expression while downregulating Beclin-1 and LC3Ⅱ/Ⅰ expression.Network pharmacology analysis identified the PI3K/AKT signaling pathway as a key therapeutic mechanism of SXBX.Western blotting confirmed increased phosphorylation of PI3K and AKT,validating the involvement of this pathway.Conclusion In this study,we demonstrated that SXBX exerts protective effects against MIRI,primarily through the regulation of the PI3K/AKT signaling pathway and the modulation of autophagy.
Keywords：Shexiang Baoxin PillMyocardial ischemia/reperfusion injuryAutophagyNetwork pharmacologyPI3K
Publication Date：2025-10-20
Online Publishing Date：2025-10-30(First online date of this platform, not the publication date of the document)
Pages：7( 957-963 )