The Chrysophanol Alleviates Myocardial Infarction through the PI3K/AKT Pathway:Based on Network Pharmacology and Cell Experiments

MEI Lin; YAO Yueqing; XU Zanshan; AN Ning; ZHOU Xuan; CHEN Yunjie

doi:10.12102/j.issn.1672-1349.2025.15.002

Abstract：Objective:To explore the improving effects of chrysophanol(CHR)on myocardial infarction(MI)damage and its molecular mechanisms.Methods:The potential targets of chrysophanol were obtained using the PubChem and Swiss Target Prediction databases.MI-related target genes were collected from the GeneCards database.The intersection of two sets was used to identify potential targets for Chrysophanol in the improvement of MI.These targets were subjected to gene function annotation(gene ontology,GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The STRING database and Cytoscape 3.9.1 software were used to construct protein-protein interaction(PPI)network diagrams and identify potential core targets for Chrysophanol in treating MI.Molecular docking and binding affinity prediction between Chrysophanol and the core targets were performed using the Schrödinger software,and visualization was done using PyMOL.Finally,primary neonatal rat cardiomyocytes(NRCMs)were subjected to oxygen and glucose deprivation(OGD)for 6 h to establish a cell model of MI.Protein expression related targets was detected by western blot,and terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and dihydroethidium(DHE)staining were used to detect apoptosis and oxidative stress in cardiomyocytes.Results:A total of 47 intersection targets between chrysophanol and MI were identified.KEGG and GO enrichment analysis showed that chrysophanol might protect MI against damage by inhibiting apoptosis and oxidative stress in cardiomyocytes,which was closely related to phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)pathway.Further research identified SRC,matrix metalloproteinase 9(MMP9),Bcl-2,estrogen receptor 1(ESR1),heat-shock protein 90(HSP90)AA1,HSP90AB1,and mammalian target of rapamycin protein(mTOR)as potential core targets for chrysophanol in treating MI.Molecular docking showed better binding affinity between chrysophanol and the core targets,as well as the PI3K/AKT pathway-related molecule phosphati-dylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA).Experimental validation demonstrated that chrysophanol activated the PI3K/AKT pathway by OGD in cardiomyocytes.Additionally,DHE and TUNEL staining results indicated that chrysophanol could alleviate oxidative stress and apoptosis induced by OGD in cardiomyocytes(P＜0.01).However,pretreatment with LY294002(a PI3K inhibitor)significantly weakened the effects of chrysophanol in inhibiting oxidative stress and apoptosis(P＜0.01).Conclusion:Chrysophanol protects cardiomyocytes against oxidative stress and apoptosis by activating PI3K/AKT signaling pathway,thereby improving myocardial infarction.