This study aims to explore the molecular mechanism of Astragali Radix-Codonopsis Radix (AR-CR) herb pair in the treatment of atherosclerosis (AS) based on network pharmacology,molecular docking and experimental verification.Firstly,the active substances of AR-CR herb pair were obtained,the target of the pair was predicted,and the target genes related to atherosclerosis were screened,by searching for TCMSP,PubChem,SwissTargetPrediction,UniProt,GeneCards and other databases.Then,the Venny platform,STRING database and Cytoscape (Version 3.8.2) software were used for topology analysis to obtain the key targets of AR-CR herb pair in the treatment of AS.The DAVID database was used to perform GO and KEGG enrichment analysis on the obtained key targets,and the molecular docking of core proteins and active substances was completed with Auto Dock tools and Auto Dock cina.Finally,oxidized low-density lipoprotein (ox-LDL) was used to induce human umbilical vein endothelial cells,and an atherosclerotic cell model was established for in vitro biological verification.Thirty-four active compounds were obtained from AR-CR in total,and 426 potential compound targets were predicted.By communicating with 875 AS targets,69 key targets for the treatment of AS were obtained,and four active compounds,including 3,9-di-O-methylnissolin,7-methoxy-2-methyl isoflavone,5α-stigmastan-3,6-dione and luteolin and serine/threonine-protein kinase (AKT1),tumor protein p53 (TP53),Mitogen-activated protein kinase 3 (MAPK3) and other 25 core targets were screened out.KEGG pathway enrichment analysis showed that the key pathways were advanced glycation end products (AGE) / receptor of advanced glycation end products (RAGE) signaling pathway and lipid-atherosclerosis signaling pathway.The results of molecular docking indicated that the four main active compounds could be connected with the core target proteins,and the bond activity of TP53 was stronger.The results of the in vitro experiment made clear that low,medium and high dose of AR-CR could enhance the proliferation of atherosclerotic model cells,inhibited their apoptosis,and boosted the expression of TP53 mRNA and TP53 protein.In summary,this study preliminarily reveals that the mechanism of AR-CR in the treatment of AS was related to TP53 factor predicted by network pharmacology and molecular docking.Via modulation of TP53 factor,AR-CR can promote the proliferation of AS model cells and inhibit their apoptosis,which provides a theoretical basis for clinical treatment of AS.

"> Astragali Radix-Codonopsis Radix, atherosclerosis, network pharmacology, molecular docking, TP53, experimental verification