Elucidating the anti-lung cancer mechanisms of Notoginsenoside R1 using network pharmacology

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, underscoring the urgent need for more effective therapeutic strategies. Notoginsenoside R1 (NGR1), a major bioactive component derived from Panax notoginseng, exhibits diverse pharmacological properties. However, its molecular mechanisms against LC have not been fully elucidated. This study employed a network pharmacology approach to investigate the potential anti-LC mechanisms of NGR1. Methods: Relevant targets of NGR1 and LC were identified using precise PubMed MeSH terms and data mining from GeneCards, the Traditional Chinese Medicine Systems Pharmacology (TCMSP), HERB, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Shared targets were determined through Venn diagram analysis. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized with Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the associated biological functions and signaling pathways. Results: A total of 36 intersecting genes were identified as common targets of NGR1 and LC. The PPI network revealed key interactions among these targets, from which 10 hub genes were identified. GO analysis indicated that these targets were mainly involved in the establishment or maintenance of transmembrane electrochemical gradients, phosphatidylinositol 3-kinase complex (class IA), and steroid hormone binding. KEGG analysis showed significant enrichment in the AGE-RAGE signaling pathway involved in diabetic complications, suggesting its relevance to LC progression. Conclusions: This study highlights the multi-target and multi-pathway characteristics of NGR1 in LC treatment, offering a theoretical foundation for future drug development.