Objective  To analyze the multi-target regulatory network and molecular mechanism of Aconitum Heterophyllum in the treatment of gout based on a multidimensional computational strategy.

Methods  Active components of Aconitum Heterophyllum were obtained through IMPPAT database and literature mining. Their targets were predicted using SwissTargetPrediction. By combining gout-related targets from GeneCards, an intersection map was constructed to identify potential therapeutic targets. A "component-target" network was constructed using Cytoscape. Protein-protein interaction (PPI) analysis was performed on core targets through the STRING platform. GO functional and KEGG pathway enrichment analysis were conducted on intersecting targets of Aconitum Heterophyllum and gout. Molecular docking and dynamic simulations were performed on core targets and their corresponding active components.

Results  Four core targets, including tyrosine protein kinase (SRC), serine/threonine protein kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), and interleukin 6 (IL-6), were identified through screening. GO functional enrichment analysis yielded 870 entries, with biological processes primarily involving PI3K-AKT signaling regulation, and molecular functions primarily being kinase activity. KEGG pathway analysis indicated that Aconitum Heterophyllum functions by regulating 177 pathways, including insulin resistance. Molecular docking experiments showed that lappaconitine had the lowest binding energy with AKT1. Molecular dynamics simulations demonstrated that the complex remained stable within 200 ns.

Conclusion  Aconitum Heterophyllum may exert multidimensional anti-gout effects through the PI3K-AKT signaling axis by synergistically acting on four core targets, including STAT3 and AKT1, via active components such as lappaconitine, providing computational biology evidence to elucidats its multi-component, multi-target, multi-pathway mechanism of action.

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