Objective  To explore the mechanism of Salvia miltiorrhiza in treating non-small cell lung cancer (NSCLC) using network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations.

Methods The main active components of Salvia miltiorrhiza were screened from the TCMSP database. Target prediction for these active components was performed using the SwissTargetPrediction and PharmMapper databases. Lung cancer-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The intersection of Salvia miltiorrhiza targets and lung cancer targets were identified as the Salvia miltiorrhiza-lung cancer targets. Differential analysis was conducted on TCGA-LUAD&LUSC and GSE159857 datasets to obtain common differentially expressed genes. The intersection of these genes with the Salvia miltiorrhiza-lung cancer targets was used to identify the core targets of Salvia miltiorrhiza in treating NSCLC. GO and KEGG enrichment analyses were performed to investigate the involved biological processes and signaling pathways. The protein-protein interaction  network of the core targets was constructed using the STRING database and Cytoscape 3.10.0 software. Molecular docking verification of the core targets was performed using AutoDock Tools 1.5.6 and AutoDock Vina 1.2.0. Molecular dynamics simulations of the molecular docking complexes were conducted using Gromacs 2022.4 software.

Results In this study, 26 active components of Salvia miltiorrhiza were screened and 61 core targets of Salvia miltiorrhiza against NSCLC were identified. The active components of Salvia miltiorrhiza exert therapeutic effects on NSCLC through biological processes such as cell cycle regulation, extracellular matrix remodeling, oxidative stress response, and metabolic reprogramming, as well as through signaling pathways including p53, PARP, AMPK, and NF-κB. These components inhibit the malignant progression of NSCLC by directly targeting CDK4, AURKB, PLK1, CDK1, and TYMS. Among these, Tanshinone IIA exhibited the strongest binding affinity with CDK4, forming a stable complex.

Conclusion  Salvia miltiorrhiza exerts therapeutic effects on NSCLC through the synergistic regulation of multiple biological processes, signaling pathways, and targets.

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