关键词: 网络药理学, 分子对接技术, 锦灯笼, 白血病

Abstract:

Objective To explore the effect of Physalis Calyx seu Fructus （PCF） on the occurrence and development of leukemia based on network pharmacology， and to clarify the main targets and signaling pathway-related mechanism of its bioactive components. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） database was used to search its bioactive components and corresponding potential targets with “Physalis Calyx seu Fructus” as the keyword； the potential targets were evaluated and predicted with Protein Data Bank （PDB） and Swiss Target Prediction website； GeneCards database， Online Mendelian Inheritance in Man （OMIM） database and DrugBank database were used to search the relevant targets with “leukemia” as the keyword. The bioactive component targets of PCF and leukemia target were intersected by Draw Veen Diagram online software， and the intersected targets were the targets of PCF acting on leukemia； the network information of protein-protein interaction （PPI） of intersection target proteins was obtained and visualized with STRING database； DAVID database was used for Gene Ontology （GO） biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis of intersection genes； topological analysis on PPI network was performed with Cytoscape 3 7.2 to screen the core targets and the core active components； the molecular docking verification was performed with AutoDock and PyMol. Results After screening the retrieval results of TCMSP database， 6 active components of PCF were obtained； 29 common targets of PCF and leukemia were collected； GO enrichment analysis mainly involved the development of hematopoietic and lymphoid organs， protein metabolism regulation， apoptosis and other biological processes； KEGG enrichment analysis mainly included cancer pathway， tumor necrosis factor （TNF）， T cell receptor （TCR） and other signal pathways. Ten core targets such as protein kinase B1 （AKT1） and cysteinyl aspartate specific proteinase-3（Caspase-3） were obtained by topological network analysis， combined with KEGG signaling pathway， the core active components Sitosterol and Gramisterol were obtained. The results of molecular docking showed that the docking energy of Sitosterol with proto-oncogene （JUN）， Gramisterol with AKT1 and Caspase-3 were －6.0 kcal·mol^－1，indicating the docking was good. Conclusion The main active components of PCF， such as Sitosterol and Gramisterol， may affect the occurrence and development of leukemia by regulating JUN， AKT1， Caspase-3 and other genes and participating in cancer pathway， TCR and other signaling pathways.

Key words: Network pharmacology, Molecular docking technology, Physalis Calyx seu Fructus, Leukemia