Background:This study pioneers a network pharmacology-based approach and in silico molecular docking and visualization approaches to predict the potential molecular mechanisms involved in treatment of lung cancer with...Background:This study pioneers a network pharmacology-based approach and in silico molecular docking and visualization approaches to predict the potential molecular mechanisms involved in treatment of lung cancer with Lingzhi(Ganoderma lucidum).Methods:The active ingredients of Ganoderma lucidum were screened in the Traditional Chinese Medicine Systems Pharmacology database,and corresponding potential targets of these active ingredients were queried.Then potential targets for the treatment of lung cancer were separately queried using the GeneCards database.The overlapping targets of the active ingredients and lung cancer treatment were further analyzed in silico by calculating degree values and conducting literature searches.A protein-protein interaction network was constructed for these overlapping targets using the STRING database,and a“drug-ingredient-target”network was created using Cytoscape 3.7.1 software.Gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for key targets using Metascape.Finally,the key molecules were examined using molecular docking in Autodock 3.7 software,and the representative docking results were visualized using PyMol software.Results:A total of 14 active ingredients were identified,including 3 key ingredients(ganolucidic acid E,ergosta-4,6,8(14),22-tetraene-3-one,and beta-sitosterol)and 8 key targets.Gene ontology analysis and KEGG enrichment showed that Ganoderma lucidum may act on 10 key signaling pathways,such as the neuroactive ligand-receptor interaction pathway,calcium signaling pathway,and cyclic adenosine monophosphate signaling pathway,to regulate neuroactivity,ion homeostasis,and other processes,thus inhibiting the progression of lung cancer.Molecular docking results predicted that among the 8 key targets,mu-type opioid receptor,transforming growth factor beta-1 proprotein,and apoptosis regulator BAX exhibit better docking with these ligands.Conclusion:The preliminary results of this study identified potential active ingredients of Ganoderma lucidum for the treatment of lung cancer,and putative mechanisms of action,which could provide a theoretical basis for further experimental studies on anticancer efficacy.展开更多
文摘Background:This study pioneers a network pharmacology-based approach and in silico molecular docking and visualization approaches to predict the potential molecular mechanisms involved in treatment of lung cancer with Lingzhi(Ganoderma lucidum).Methods:The active ingredients of Ganoderma lucidum were screened in the Traditional Chinese Medicine Systems Pharmacology database,and corresponding potential targets of these active ingredients were queried.Then potential targets for the treatment of lung cancer were separately queried using the GeneCards database.The overlapping targets of the active ingredients and lung cancer treatment were further analyzed in silico by calculating degree values and conducting literature searches.A protein-protein interaction network was constructed for these overlapping targets using the STRING database,and a“drug-ingredient-target”network was created using Cytoscape 3.7.1 software.Gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for key targets using Metascape.Finally,the key molecules were examined using molecular docking in Autodock 3.7 software,and the representative docking results were visualized using PyMol software.Results:A total of 14 active ingredients were identified,including 3 key ingredients(ganolucidic acid E,ergosta-4,6,8(14),22-tetraene-3-one,and beta-sitosterol)and 8 key targets.Gene ontology analysis and KEGG enrichment showed that Ganoderma lucidum may act on 10 key signaling pathways,such as the neuroactive ligand-receptor interaction pathway,calcium signaling pathway,and cyclic adenosine monophosphate signaling pathway,to regulate neuroactivity,ion homeostasis,and other processes,thus inhibiting the progression of lung cancer.Molecular docking results predicted that among the 8 key targets,mu-type opioid receptor,transforming growth factor beta-1 proprotein,and apoptosis regulator BAX exhibit better docking with these ligands.Conclusion:The preliminary results of this study identified potential active ingredients of Ganoderma lucidum for the treatment of lung cancer,and putative mechanisms of action,which could provide a theoretical basis for further experimental studies on anticancer efficacy.
