ETHNOPHARMACOLOGICAL RELEVANCETraditional Chinese Medicine (TCM) has a history of thousands of years in China. The Tongfeng Qingxiao Formula (TFQXF), after decoction and oral administration, has shown significant therapeutic effects on Gouty arthritis (GA). TCM is often considered an experiential medicine, lacking modern scientific research, and the efficacy of TFQXF faces the same issue. This is not conducive to the protection and further development of TCM, which could help more patients. Therefore, this study aims to elucidate the mechanism of action of TFQXF from the perspectives of animal experiments, cellular experiments, and high-throughput gene sequencing. The goal is to provide further protection and development for the TCM formula TFQXF, and offer new references for the treatment of GA.AIM OF THE STUDYTo improve gouty arthritis by TFQXF based on the neutrophil extracellular trapping network.MATERIALS AND METHODSMonosodium Urate (MSU) intervention in Sprague-Dawley (SD) male rats to construct a GA model with TFQXF administration. After 21 days of testing: ds DNA/Neutrophil Extracellular Traps (NETs) by PicoGreen spectrophotometry, Myeloperoxidase (MPO) and Neutrophil Elastase (NE) by Enzyme-Linked Immunosorbent Assay (ELISA); synovial tissue of ankle: MPO and NE by immunohistochemistry; gene and protein expression levels of MPO, NE, CXCL 9 and CXCL10 by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot. Cell experiment: Primary neutrophils of SD male rats were treated with MSU molding and different concentrations of TFQXF containing serum, observed the cell survival rate, Reactive Oxygen Species (ROS) level and apoptosis; collected the cell culture supernatant, measured ds DNA/NETs by PicoGreen fluorescence spectrophotometry, and measured the expression levels of Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Transforming Growth Factor-beta 1 (TGF-β1), MPO and NETs by immunofluorescence. High-throughput sequencing and bioinformatics screening of key target genes and validation using Western blot and RT-qPCR.RESULTSThe expression levels of ds DNA/NETs, MPO and NE in GA rats, and the expression levels of MPO, NE, CXCL 9 and CXCL10 in synovial tissue were decreased after the administration of TFQXF. MSU intervention promoted ROS generation and inhibited neutrophil apoptosis, increased the expression levels of ds DNA/NETs, IL-6, TNF-α, decrease in TGF-β1, and fluorescence in MPO and NE. TGF-β1 level increased after TFQXF containing serum and diclofenac sodium intervention, while the remaining indexes decreased. The validation of the key genes COL1A1, COL3A1 and MMP 2 showed that the level increased under the intervention of MSU and decreased under the intervention of TFQXF containing serum and diclofenac sodium.CONCLUSIONSTFQXF may inhibit neutrophil recruitment and release of NETs, reduce inflammation, and promote the return of GA inflammation to health. In addressing the global challenge of GA, TCM offers valuable references and perspectives for consideration.