Objective To employ network pharmacology combined with molecular docking, and to systematically predict the potential targets and signaling pathways underlying the anti-lung cancer effect of Scutellaria radix, thereby clarifying its mechanism of action at the molecular binding level.

Methods Active components of Scutellaria radix were screened with oral bioavailability ≥ 30% and drug-likeness ≥ 0.18 as the thresholds, and their targets were predicted via multiple databases. The overlapping targets with lung cancer were then used to construct a protein-protein interaction network, followed by Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Target-specific inhibitors were adopted as positive controls to verify binding activity and compare binding sites through molecular docking, while absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted in parallel.

Results A total of 36 active components were identified, corresponding to 104 overlapping targets for lung cancer, including 17 core targets such as cellular tumor antigen p53 (TP53), RAC-alpha serine/threonine-protein kinase (AKT1), and interleukin-6 (IL6). These targets were markedly enriched in tumor-related pathways, such as advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), interleukin-17 (IL-17), tumor necrosis factor (TNF), and phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt). Baicalein, wogonin, oroxylin A, and baicalin demonstrated strong binding activity with core targets, with baicalinide exhibiting superior binding affinity to prostaglandin-endoperoxide synthase 2 (PTGS2) compared to the positive control celecoxib. For TP53 and IL6 targets, all four components shared four key amino acid residues with their respective positive inhibitors, structurally confirming their inhibitor-like targeting characteristics. ADMET predictions suggested satisfactory oral absorption potential and metabolic safety for most components.

Conclusion Scutellaria radix exerts anti-lung cancer effects through the synergistic actions of multiple components, targets, and pathways, providing structural biological evidence and a theoretical foundation for further development.

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