Study On The Material Basis Of Anti-lung Cancer Of Gleditsiae Fructus Abnormalis Based On LC-MS And Network Pharmacology

Objective:The chemical components of the methanol extract of Gleditsiae fructus abnormalis and the blood components were analyzed by liquid chromatography-mass spectrometry,and the material basis and related mechanism of Gleditsiae fructus abnormalis on lung cancer were explored by network pharmacology,so as to provide experimental basis for further screening the anticancer active components of Gleditsiae fructus abnormalis and establishing quality markers.Methods:1.In order to clarify the material basis of Gleditsiae fructus abnormalis,the chemical constituents of Gleditsiae fructus abnormalis were analyzed and characterized by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UHPLC-QTOF-MS/MS）.According to the different structural types of the compounds,the fragmentation rules were summarized for the identification of the chemical constituents of the drug.2.UHPLC-QTOF-MS/MS technique was used to analyze the components of Gleditsiae fructus abnormalis in vitro.After intragastric administration of Gleditsiae fructus abnormalis extract to rats,serum was taken to analyze the components of Gleditsiae fructus abnormalis into blood,which provided a basis for the study of the pharmacodynamic material basis of Gleditsiae fructus abnormalis.3.Based on the network pharmacology research method,the blood components of the preliminarily determined prototype of Gleditsiae fructus abnormalis were used as the research object.Target prediction,PPI network,GO and KEGG enrichment were used to explore the key targets of its anti-tumor effect,analyze its main action pathways and biological processes,and then explore the drug-component-target-disease network relationship of Gleditsiae fructus abnormalis,and clarify its anti-lung cancer material basis and action pathway.Results:1.A total of 117 compounds were identified,including 37 flavonoids,15 chlorogenic acids,23lignans,18 organic acids and 24 saponins.The study of the chemical constituents of the drug provides a basis for the study of its pharmacodynamic material basis.2.Sixteen compounds were identified as Juglanin D,Protocatechuic aldehyde,G（8-O-4）G^dihydro,Schaftoside,Caffeic acid,Syringaresinol-glc,3-formylindole,Apigenin-C-glc-rha,Vanillin,Dimethoxyflavanonol,G（8-O-4）S^glycerol,Coniferaldehyde,Secoisolariciresinol,Apigenin,Echinocystic acid;and 14 metabolites were identified.3.Finally,96 potential targets for the treatment of lung cancer were obtained.Nine lung cancer-related components(Echinocystic acid,Coniferaldehyde,Caffeic acid,Apigenin,3-formylindole,Vanillin,Syringaresinol-glc,Protocatechuic aldehyde,Juglanin D and G（8-O-4）G^dihydro)were screened.PPI network and drug-component-disease-target interaction network were established,and 20 core targets（CCND1/HIF1A/PTGS2/ERBB2/MMP9/MAPK1/MDM2/PIK3CA/TLR4/PPARG/AR/EP300/IL2/MMP2）were screened out through PPI network.Twenty key signaling pathways were screened by KEGG analysis.Conclusion:In this study,UHPLC-QTOF-MS/MS technology was used to combine the relevant literature and reference information to study the chemical composition of Gleditsiae fructus abnormalis,and the chemical composition of Gleditsiae fructus abnormalis was comprehensively characterized.Studies have shown that the main chemical components of Gleditsiae fructus abnormalis are triterpenoid saponins,flavonoids,chlorogenic acids and organic acids.Among them,the mother nucleus of triterpenoid saponins is mainly spinosad acid and oleanane type,and flavonoids mainly exist in the form of carbon glycosides.The results of serum pharmacochemistry showed that the metabolites of Gleditsiae fructus abnormalis extract in serum were mostly organic acids,and the common metabolic reactions were reduction,sulfonation,glucuronidation and methylation.Other blood components mostly exist in the form of prototype.The results of network pharmacology showed that nine components,including Echinocystic acid,Coniferaldehyde,Caffeic acid,Apigenin,3-formylindole,Vanillin,Syringaresinol-glc,Protocatechuic aldehyde,Juglanin D and G（8-O-4）G^dihydro,were related to the treatment of lung cancer.Some key signaling pathways were screened by KEGG analysis.Combined with core PPI target analysis,pathway Lipid and atherosclerosis and EGFR tyrosine kinase inhibitor resistance were key signaling pathways related to the treatment of lung cancer with Gleditsiae fructus abnormalis.