Revealing the therapeutic mechanism of Hedyotis diffusa-Sculellaria barbata in lung cancer through network pharmacology and molecular docking

Abstract

Abstract Objective: Elucidating the therapeutic mechanism of the combination of Hedyotis diffusa and Sculellaria barbata for lung cancer through network pharmacology and molecular docking. Method: We employed network pharmacology and molecular docking techniques to identify effective components and targets using the TCMSP database. Furthermore, relevant lung cancer targets were retrieved from the GEO database. The main targets of Hedyotis diffusa- Sculellaria barbata for lung cancer treatment were visualized using Cytoscape. Cytoscape 3.7.1 and the STRING database platform were utilized to respectively construct the active ingredient-target network map and the protein-protein interaction (PPI) network of common target proteins. To identify the therapeutic targets of the combination of Hedyotis diffusaand Sculellaria barbata for lung cancer treatment, a topological analysis was performed using cytoNCA, followed by network integration. The molecular targets and genes obtained were subjected to gene ontology (GO) function enrichment analysis and KEGG pathway analysis. The molecular docking of key action targets and major active ingredients was conducted using the AutoDockTools 1.5.6 software. Results: A total of 32 bioactive constituents were identified in the medicinal combination of Hedyotis diffusa-Sculellaria barbata, comprising 7 compounds from Hedyotis diffusa and 25 compounds from Sculellaria barbata. Notably, quercetin, baicalin, flavonoids, and luteolin emerged as key components with significant relevance to lung cancer treatment. The target analysis revealed AKT1, HSP90AA1, SRC, CASP3, and MAPK1 as potential therapeutic targets for lung cancer treatment. The GO enrichment analysis revealed the involvement of 376 biological process-related items, 50 cell composition-related items, and 116 molecular function-related items in the targets. A total of 51 pathways were identified through KEGG pathway enrichment analysis. The molecular docking results confirmed the stable binding of ATK1 to the active ingredients baicalein and luteolin, HSP90AA1 to baicalein and flavonoids, SRC to all four active ingredients, and CASP3 to quicaletin and luteolin. Conclusion: The treatment of lung cancer with Hedyotis diffusa-Sculellaria barbata exhibits the characteristics of being multi-component, multi-target, and multi-pathway, thereby providing a scientific foundation for both basic research and clinical application.