Deciphering the Molecular Basis: Integrative Multi‐Method Analysis of Bioactive Constituents and Their Anti‐Lung Cancer Mechanisms in Clinical Traditional Chinese Medicine Formulations

ABSTRACT

Despite variations in the composition of traditional Chinese medicine (TCM) formulas for lung cancer used in clinical practice, they show consistent clinical efficacy. This study employed an integrated approach combining network pharmacology, bioinformatics, and in vitro experiments to analyze 45 clinical prescriptions. From the 188 herbs identified, licorice and atractylodes rhizome were the most frequently used. Analysis revealed seven key active compounds, including quercetin and stigmasterol, acting on 149 shared targets, with significant enrichment in pathways such as PI3K/AKT. Molecular docking confirmed strong binding between core compounds and targets like PRKACA. Bioinformatics analysis of TCGA data further reveals that MMP9 may promote tumor invasion and metastasis by degrading the extracellular matrix. In vitro, quercetin and stigmasterol inhibited A549 cell proliferation and induced apoptosis, with quercetin suppressing PI3K/AKT activation. The findings indicate that licorice and atractylodes rhizome may play a synergistic role, and quercetin acts as a key anti‐cancer compound by inhibiting the PI3K/AKT pathway, elucidating a common pharmacological basis for these TCM formulas.