To explore the mechanism of action of Tongjing Huoluo Formula in treating rheumatoid arthritis(RA) using network pharmacology and molecular docking techniques,optimize the extraction process of its essential oil components,and verify its pharmacological effects.Methods:Active components of Tongjing Huoluo Formula were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and an active component-target network was constructed.RA disease targets were screened,and a protein-protein interaction(PPI) network was built.Potential therapeutic targets were identified,followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.A “drug-active component-target-pathway” network was constructed to analyze the core components and targets of Tongjing Huoluo Formula in treating RA and verify them using molecular docking.Single-factor experiment was used to determine the factors and ranges for the extraction process.The Box-Behnken response surface method was employed to optimize the extraction process with essential oil yield as the response indicator.The antioxidant capacity of Tongjing Huoluo Essential Oil was measured using the 1,1-diphenyl-2-trinitrophenylhydrazine(DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS+) radical scavenging methods.Results:A total of 182 active components were screened from Tongjing Huoluo Formula,interacting with 215 targets.The core active components that improved RA were quercetin,apigenin,luteolin,kaempferol,and myricetin.Core targets included prostaglandin-endoperoxide synthase 2(PTGS2),nuclear factor kappa B(RELA),AKT serine/threonine kinase 1(AKT1),heat shock protein 90AB1(HSP90AB1),and caspase-3(CASP3).The formula involved multiple signaling pathways,such as oxidative stress,inflammation,and glucose-lipid metabolism.Molecular docking revealed that the core active components had high affinity with the core targets.The optimal extraction process for Tongjing Huoluo Essential Oil was a particle size of 60 meshes,liquid-material ratio of 10 mL/g,extraction time of 3.5 h,and extraction temperature of 110 °C,yielding 0.483%.The essential oil at a concentration of 200 μg/mL showed high antioxidant activity.Conclusion:Tongjing Huoluo Formula exerts its pharmacological effects in treating RA through multi-component,multi-pathway,and multi-target synergistic actions,including anti-inflammatory,antioxidant,and anti-apoptotic mechanisms.The essential oil obtained under optimal extraction conditions demonstrated high antioxidant activity in vitro,which warrants further research and utilization.