Résumé
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.
Résumé
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.
Résumé
@#The chemical constituents from 70% ethanol petroleum ether and n-butanol extractions of Callerya nitita Benth.var.hirsutissima.Z.Wei. were separated by preparative high-performance liquid chromatographic techniques, including repeated column chromatography over macroporous adsorption resin, silica gel, ODS, Sephadex LH-20. The structures of the compounds were identified by their physicochemical properties, spectral data, and mass spectrometry data, in comparison with literature. In our research, one triterpenoids, taraxerone (1), and twenty flavonoids, including genistein-4′-O-β-glucoside (2), 5-hydroxy-4′-methoxyisoflavone-7-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (3), biochanin A 7-O-β-D-apiofuranosyl-(1→5)-β-D-apiofuranosyl- (1→6)-β-D-glucopyranoside (4), formononetin-7-O-β-D-galactopyranoside (5), 5,7-dihydroxy-3′,4′-dimethoxyisoflavone (6), biochanin A-7-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (7), 5, 7-dihydroxyisoflavone-4′-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranoside (8), formononetin-7-O-D-apio-β-D-furanosyl(l→2)-β-D-glucopyranoside (9), 4′-hydroxy-3′-methoxyisoflavone-7-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (10), prunetin (11), prunetin 4′-O-β-D-glucopyranoside (12), pratensein7-O-β-D-glucoside (13), 8-methoxyisoformononetin (14), genistein (15), 3′-hydroxybiochanin A (16), biochanin A (17), 5,7-dihydroxy-3′,5′-dimethoxyisoflavone (18), ononin (19), isoformononetin (20), 5,7,3′,4′-tetrahydroxyflavone (21) were isolated from the two extract parts.Compounds 1-10, 12-14, 16-18, 20 were obtained from this plant, and it is the first time to investigate the plant for the first time.