Mechanism of Active Steroid Alkaloids from Solanum nigrum Against Non-small Cell Lung Cancer： Based on Network Pharmacology / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the potential targets and pathways of steroid alkaloids<italic> </italic>from<italic> Solanum</italic> <italic>nigrum</italic> （SASN） in the treatment of non-small cell lung cancer （NSCLC） and analyze the possible mechanism. Method:The active SASN against NSCLC were searched from literature. Then potential targets of SASN were screened through SwissTargetPrediction and PharmMapper， and those of NSCLC through GeneCards. Venny was employed to yield the common targets of the two， and Cytoscape to construct the 'medicinal-component-disease-target' network. Metascape was applied to enrich the Gene Ontology （GO） terms and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of the common targets， and STRING was used to generate the protein-protein interaction （PPI） network， followed by screening of key targets by Cytoscape. Finally， Western blot was used to verify the effects of the medicinal on key targets. Result:A total of 6 active SASN were screened out： solasonine， solamargine， solasodine， solanocapsine， solanidine， and <italic>N</italic>-methylsolasodine， which had 96 potential anti-NSCLC targets. These targets mainly involved the pathways in cancer， proteoglycans in cancer， and Forkhead box protein O （FoxO） pathway. PPI network analysis demonstrated 15 key anti-NSCLC targets of SASN， such as mitogen-activated protein kinase （MAPK）1， MAPK8， MAPK14， protein kinase B （Akt1）， signal transducer and activator of transcription 3 （STAT3）， and proto-oncogene tyrosine protein kinase （SRC）. Meanwhile， Western blot results showed that SASN could significantly down-regulate the expression of the key proteins Akt1， SRC， and STAT3. Conclusion:We predicted the potential targets and pathways of SASN against NSCLC and obtained 15 key targets， from which we selected three key proteins for validation. The validation results were consistent with the prediction results. This paper is expected to lay a scientific basis for the subsequent in-depth study of the mechanisms of SASN against NSCLC.