ABSTRACT
Aim To explore the mechanism of action of the active ingredients of Callerya nitida var.hirsutissima corresponding to the target gene in the treatment of triple-negative breast cancer(TNBC), using network pharmacology, molecular docking technology and in vitro experimental verification.Methods Based on literature research and combined with database screening, the main active components of Callerya nitida var.hirsutissima and the related targets of TNBC were obtained.Intersection genes were found to construct a protein interaction(PPI)network diagram, and core targets were screened according to the size of the correlation.A core target interaction network model of "Traditional Chinese Medicine-Ingredients-Targets-Disease" was constructed.The intersection targets were analyzed for gene GO function and KEGG pathway enrichment analysis.Finally, molecular docking and in vitro experimental verification of the selected components and the target were carried out.Results A total of 38 active components of Callerya nitida var.hirsutissima were collected, as well as 388 related potential targets, 3 919 TNBC targets, and 277 Callerya nitida var.hirsutissima therapeutic targets for TNBC.It mainly acted on multiple targets such as PIK3R1, PIK3CA, MAPK1, AKT1, SRC, etc.In in vitro experiments, it could be seen that the chloroform fraction of Callerya nitida var.hirsutissima and the monomer compounds luteolin and betulin had certain inhibitory effects on cell proliferation.All groups could inhibit the expression of VEGFA, AKT, PIK3CA, CDK1, CDK4 within the range of administration concentration.Conclusions Based on network pharmacology and molecular docking methods, this study explores the possible targets and signaling pathways of Callerya nitida var.hirsutissima in the treatment of TNBC, and conducts in vitro verification experiments to further verify the prediction of network pharmacology.
ABSTRACT
The Leguminosae perennial vines of Callerya and Millettia have many species and wide distribution， not only can be used for medicines， but also they have ornamental and insecticidal effects. With increasing demand for Spatholobi Caulis， and the reserves of wild medicinal materials are on the verge of exhaustion， resulting in the increasing number of mixtures and substitutes in the market， which makes it urgent to study the origin of Spatholobi Caulis. By referring to related literature， there are three major origins of Spatholobi Caulis， including Callerya， Millettia and Spatholobus. Callerya is separated from Millettia， they are divided and united for many times， now the official website of Flora of China has accepted the revision of them as two genera. This paper intends to compare the chemical components and pharmacodynamic effects of Callerya and Millettia， aiming to explore the similarities and differences between the two genera， so as to determine the rationality and necessity of separating Callerya from Millettia. After comparing， it was found that the chemical composition and pharmacodynamic effects of the two genera were different， which supported the separation of Callerya from Millettia， and it was not recommended to mix use of them.
ABSTRACT
In this paper, the molecular mechanism of Spatholobi Caulis in the treatment of non-small cell lung cancer(NSCLC) was studied through network pharmacology and molecular docking analysis. With traditional Chinese medicine(TCM) Spatholobi Caulis as the study object, active ingredients of Spatholobi Caulis and corresponding potential drug targets were obtained from Traditio-nal Chinese Medicine Pharmacology Platform(TCMSP) database; GeneCards database was used to collect cancer-related genes; Cytoscape software was used to build Spatholobi Caulis active ingredient-target-pathway relationship network. DAVID database was used for GO and KEGG enrichment analysis of targets, KEGG signaling pathway was visualized, and compounds were screened out for molecular docking. Finally, in vitro experiments on human lung cancer cells, A549 treated with luteolin and licochalcone A were used to preliminarily verify the core targets and pathways, cell proliferation was detected by CCK-8 method, and expressions of caspase-3 and Bax protein were detected by Western blot. A total of 23 active components and 170 potential drug targets were selected from Spatholobi Caulis, involving 127 pathways in total. Molecular docking results showed that licochalcone A,(Z)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-phenyl) ethyl] acrylamide, consumeclose grain successfully docked with the key target EGFR, and binding energy of the three compounds was less than-5 kcal·mol~(-1). CCK-8 results showed that luteolin, licochalcone A, and Spatholobi Caulis extract had the inhibitory effect on human lung cancer A549 cells. Western blot showed that luteolin, licochalcone A and Spatholobi Caulis extract could induce cell apoptosis by increasing the expressions of pro-apoptotic factors caspase-3 and Bax. In this study, the anti-lung cancer effect of Spatholobi Caulis was studied through network pharmacology and molecular docking, in order to provide ideas for the molecular mechanism of Spatholobi Caulis in the treatment of lung cancer.