Protective effect of Lonicerae Japonicae Flos extract against doxorubicin-induced myocardial injury in mice and the possible mechanisms
XIA Shicheng
WEI Huifang
HONG Weican
ZHANG Yuming
YIN Feiyang
ZHANG Yixin
ZHANG Linlin
GAO Qin
YE Hongwei
Abstract：Objective To evaluate the protective effect of Lonicerae Japonicae Flos(LJF)extract against doxorubicin(DOX)-induced cardiotoxicity(DIC)and explore the possible mechanisms.Methods Network pharmacology,bioinformatics analysis and molecular docking were used to predict the targets of the core components of LJF.In a mouse model of DOX-induced myocardial injury,the protective effects of different doses of LJF extract were evaluated and the underlying mechanisms were explored by detecting the changes in mouse myocardial functions,myocardial enzymes,myocardial pathologies,and the expressions of inflammatory factors and pyroptosis-related proteins.Results The 10 core ingredients of LJF showed strong binding to AKT,EGFR,and GSK3β.In the animal experiment,the DOX-treated mice,compared with the sham-treated mice,had significantly decreased cardiac output,stroke volume,left ventricular ejection fraction,left ventricular fraction shorting,elevated serum levels of CK-MB and LDH,increased myocardial expressions of IL-18 and IL-1β,obvious myocardial damage,increased expression levels of NLRP3,caspase-1,GSDMD and GSDMD-N,and reduced expressions of EGFR,p-AKT and p-GSK3β proteins in the myocardial tissues.LJF treatment obviously improved myocardial function,decreased myocardial expressions of IL-18,IL-1β,NLRP3,caspase-1,GSDMD and GSDMD-N proteins,and increased the expressions EGFR,p-AKT and p-GSK3β proteins in DOX-treated mice.Conclusion LJF extract alleviates DOX-induced myocardial injury in mice possibly by reducing myocardial inflammation and pyroptosis via targeting EGFR,AKT and GSK3β to regulate the ErbB signaling pathway.
Keywords：network pharmacologyLonicerae Japonicae Flos extractdoxorubicinmolecular dockingpyroptosisErbB signaling pathway
Publication Date：2025-12-20
Online Publishing Date：2025-12-31(First online date of this platform, not the publication date of the document)
Pages：14( 2527-2540 )