Mechanistic study of Lonicerae Japonicae Flos (Caprifoliaceae) in non-small cell lung cancer prevention and treatment through integrative pharmacology, multi-machine learning, artificial intelligence, and in vitro experiments

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (Caprifoliaceae) (LJF), an herb with the homology of medicine and food, is traditionally utilized for its heat-clearing, detoxifying, and anticancer properties. Yet, the mechanism by which LJF may assist in the treatment of non-small cell lung cancer (NSCLC) remains unclear. AIM OF THE STUDY: To elucidate the potential mechanisms of LJF in the treatment of NSCLC through phytochemical analysis, network pharmacology, machine learning, and in vitro experimental validation. MATERIALS AND METHODS: LJF was analyzed for its components using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The active compounds and targets of LJF were identified from TCMSP, and NSCLC-related targets were retrieved from GeneCards, DisGeNET and OMIM. Network pharmacology and multi-machine learning algorithms predicted key features, and GSEA/GSVA assessed pathway enrichment. Immune infiltration analysis evaluated immune cell composition in the NSCLC microenvironment, and molecular docking was performed with AlphaFold. In vitro experiments assessed LJF's effects on A549 cells, and Western blot analyzed protein expression. RESULTS: Network pharmacology and multi-machine learning indicated that PECAM1 and SPP1 are potential targets for LJF in the treatment of NSCLC. GSEA and immune infiltration analysis suggested PECAM1 and SPP1 influence NSCLC progression and immune evasion. In vitro experiments showed that LJF significantly inhibited A549 cells proliferation, migration, and invasion. Western blot results indicated upregulation of PECAM1 and SPP1 expression under LJF treatment. CONCLUSION: LJF has an adjunctive therapeutic effect on NSCLC by regulating PECAM1 and SPP1 targets and their associated signaling pathways.