Mechanism investigation of Actinidia arguta total flavone on gout via network pharmacology and vivo experiments pharmacological verification

To clarify the therapeutic targets and signaling pathways of Actinidia arguta total flavone (AATF) in gout treatment, we integrated network pharmacology and in vivo experiments. Network pharmacology was applied to screen AATF’s anti-gout targets, construct protein-protein interaction (PPI) and drug-component-disease-target-pathway networks, and conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A dual gout rat model was established using potassium oxonate, adenine, and monosodium urate (MSU) crystals, followed by assessments including toe swelling measurement, hematoxylin-eosin (HE) staining of kidney and joint tissues, digital radiography (DR) imaging, detection of serum uric acid and xanthine oxidase (XOD) activity, enzyme-linked immunosorbent assay (ELISA) of inflammatory factors, and Western blot validation of key targets. Network pharmacology revealed that AATF modulates inflammatory responses and the tumor necrosis factor (TNF) pathway via core targets including albumin (ALB), TNF, interleukin-6 (IL-6), and tumor protein 53 (TP53). In vivo experiments showed that AATF significantly ameliorated renal and joint pathological damage, reduced serum uric acid/XOD activity, downregulated serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, cyclooxygenase-2 (COX-2) levels, and inhibited joint nuclear factor kappa B (NF-κB), extracellular signal-regulated kinase 1 (ERK1), matrix metalloproteinase 9 (MMP9) expression. Collectively, AATF exerts anti-gout effects through multi-target and multi-pathway mechanisms linked to the TNF signaling pathway, providing critical preliminary evidence for its preclinical development.