Investigating the mechanisms of Plantago major and Plantago lanceolata in non-small cell lung cancer: A study of their bioactive phytocompounds through network pharmacology, molecular docking, and integrated computational approaches.

Abstract

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer, associated with high morbidity and mortality rates. Current treatments, including surgical resection, chemotherapy, targeted therapy, and radiation, offer limited improvement in prognosis, with a low five-year survival rate. Thus, innovative therapeutic approaches are critically needed. The study utilized a network pharmacology approach to explore the phytocompounds of P. major and P. lanceolata targeting key genes in NSCLC. It involved collecting compounds of P. major and P. lanceolata using IMPPAT 2.0 and literature, screening drug-likeliness compounds using SWISS ADME, target prediction for bioactive compounds using SWISS targets, screening NSCLC-related targets using Genecards and OMIM, gene function annotation using DAVID GO and KEGG analysis, constructing a "Compounds-Targets-Pathway" network and analyzing protein interaction to identify hub genes using STRING and Cytoscape software, conducting molecular docking using Autodocktools and Autodock Vina, and lastly performing molecular dynamics simulations using GROMACS. Functional enrichment GO analysis and KEGG pathway analysis indicated that the primary mechanism of action of P. major and P. lanceolata phytocompounds in NSCLC treatment involves regulating cellular metabolism, survival, and cell cycle progression through various signaling pathways, including PKB, RA, PTP, hormone-mediated signaling, and PI3K. Molecular docking studies identified eight bioactive compounds with strong affinity for EGFR and three for MET, suggesting potential treatments for NSCLC with EGFR and MET mutations. Molecular dynamics simulations revealed that apigenin-7-O-glucoside is a promising therapeutic option for NSCLC with EGFR mutations, while scutellarein is more effective for MET mutations. The research provides the scientific basis for developing quality control standards and therapeutic applications, particularly for treating EGFR and MET mutations in NSCLC. It also highlights the need for further investigation into using P. major and P. lanceolata phytocompounds in NSCLC treatment.