To explore the antioxidant activity and mechanism of Centranthera grandiflora Benth roots based on network pharmacology and in vitro experiments.Antioxidant activity were evaluated by DPPH radical scavenging assay,ABTS radical scavenging assay,and hydroxyl radical scavenging method.The TCMSP database,and literature mining were used to collect active ingredients of C. grandiflora roots,target genes related to oxidative stress were collected through the OMIM and GeneCards database,and protein interaction networks (PPI) were constructed through the STRING database.GO and KEGG enrichment analyses were performed on the potential targets using the R language.Molecular docking of key active ingredients with potential targets using AutoDock 1.5.7 software.The results showed that C. grandiflora roots extract had a certain ability on DPPH,ABTS,and hydroxyl radicals scavenging,with IC₅₀ values of 0.166,0.054 and 0.180 mg/mL,respectively.Twenty-two active ingredients of C. grandiflora roots,86 target genes,and 84 intersection targets were collected,including STAT3,HSP90AA1,HDAC1,etc.Go function enrichment analysis found 3386 items,including molecular functions such as carbohydrate binding and nuclear receptor activity.KEGG pathway enrichment analysis found 211 items (P< 0.05),involving PI3K/AKT,and other signaling pathways related to C. grandiflora roots.The molecular docking results showed that the predicted key component,showed good binding to the core targets,binding energies <-1.2 kcal/mol.The Western blot results showed that the extract of C. grandiflora roots significantly upregulated the expression of p-PI3K and p-Akt proteins.The above results suggest that the extract of C. grandiflora roots can exert antioxidant activity by activating the PI3K-Akt signaling pathway.This study provides a reference for the study on the clinical use and application of C. grandiflora roots.