This study aims to explore the potential action mechanism of freeze-drying Panacis Quinquefolii Radix (FDPQ) on atherosclerosis (AS) based on network pharmacology and molecular docking.Firstly,the saponins of FDPQ were characterized by UPLC-Q Exactive Orbitrap-MS/MS analysis.Then,the related targets of FDPQ and AS were predicted using the SwissTargetPrediction database and GeneCards database,respectively.The overlapping targets of FDPQ and AS were obtained and subjected to GO and KEGG analysis.Further,the PPI and drug-compounds-targets-disease-pathways networks were constructed by Cytoscape software.Discovery studio software was employed to predict the docking affinity between the potential targets for AS treatments and active components from FDPQ.Finally,PC12 cells were induced by H₂O₂ to establish an oxidative damage cell model and treated with FDPQ.CCK-8 method,mitochondrial membrane potential detection,antioxidant enzyme activity determination,and qRT-PCR detection of related gene mRNA expression were used to preclinically verify the prediction results of network pharmacology.According to the results of UPLC-Q Exactive Orbitrap-MS/MS analysis,28 ginsenosides of FDPQ were identified,such as ginsenosides Rg₄ and pseudo-ginsenoside F₁₁.A total of 21 core targets including PIK3CA and VEGFA were obtained through PPI network analysis.The most significantly enriched pathway of GO and KEGG involved transmembrane receptor protein tyrosine kinase signaling pathway,focal adhesion,protein serine/threonine/tyrosine kinase activity,PI3K-Akt signaling pathway,Lipid and atherosclerosis,VEGF signaling pathway,et al.The results of molecular docking show that the main active components have a good binding affinity with the key targets.For example,pseudo-ginsenoside F₁₁ had a high affinity with the target PIK3CA.Cell experiments showed that compared with blank group,cell viability of model group decreased (P< 0.05),mitochondrial membrane potential decreased and MDA level increased (P< 0.05),SOD and CAT activities decreased (P< 0.05),PI3K/Akt expression was down-regulated;Compared with model group,FDPQ group increased cell viability (P< 0.05),mitochondrial membrane potential increased and MDA level decreased (P< 0.05),SOD and CAT activities increased (P< 0.05),PI3K/Akt expression was up-regulated.This network pharmacology-based research indicates that FDPQ’s effect on AS is characterized by multi-ingredients,multi-targets,and multi-pathways,laying a preliminary foundation for further study of its material basis and mechanism of action.