Objective To investigate the mechanism of action of the of Herba Verbenae-Campsis Flos herb pair in the treatment of thyroid nodules using network pharmacology, and to provide a reference for its clinical application.

Methods Active components and targets of the herb pair were screened via TCMSP and SwissTargetPrediction database, and disease targets of thyroid nodules were obtained from OMIM, DisGeNET and GeneCards database. The intersection of the above targets was taken to construct a protein-protein interaction (PPI) network, and core targets were screened through topological analysis with Cytoscape 3.9.1. The DAVID database was used to conduct Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and a "chemical component-target-pathway" network was built to screen key active components. Finally, MOE software was adopted to perform molecular docking verification between potential active components and key targets.

Results A total of 14 active components and 200 overlapping targets were screened out. RAC-alpha serine/threonine-protein kinase (AKT1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), and estrogen receptor 1 (ESR1) were identified as the core targets, while 4'-hydroxywogonin, artemetin, luteolin and ethyl linolenate were defined as the key active components. KEGG enrichment analysis revealed that their effects were closely associated with signaling pathways including the phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), interleukin-17 (IL-17), and tumor necrosis factor (TNF). Molecular docking verified that the key active components bound well to the core targets.

Conclusion Network pharmacology prediction combined with molecular docking verification indicated that the Herba Verbenae-Campsis Flos herb pair can exert therapeutic effects on thyroid nodules through multiple components, multiple targets, and multiple pathways, and can provide a bioinformatics-based theoretical reference for its clinical application. However, the relevant molecular regulatory mechanisms still require further verification through subsequent cellular and animal molecular biology experiments.

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