A Study On The Mechanism Of Angelica Sinensis Blood Tonic Soup For Abnormal Uterine Bleeding Based On Network Pharmacology

Objective:This study was conducted to explore the potential material basis and possible molecular mechanisms of action of Angelica sinensis blood tonic soup in the treatment of abnormal uterine bleeding(AUB)by using network pharmacology and molecular docking-related techniques.At present,the application of Astragalus membranaceus and Angelica sinensis in combination,pharmacological studies and molecular composition are relatively well studied in China,but the potential targets and possible mechanisms of action of Angelica sinensis in the treatment of AUB are not yet studied enough.Methods:The potential active ingredients of Astragalus membranaceus and Angelica sinensis were screened using the Chinese herbal systemic pharmacology database[1]and analytical platform,and the potential targets of action of the Chinese herbal active ingredients of Angelica sinensis blood tonic soup were predicted using the Uniprot platform.The OMIM,DrugBank,PharmGkb and Genecards databases were used to predict and screen their targets of function for the treatment of abnormal uterine bleeding.The intersection of drug targets and disease targets was visualised using Venn diagrams for mapping.Protein-protein(PPI)interaction networks were constructed for the key targets through the String database and Cytoscape 3.8.0 software to obtain the key components and key targets of Angelica tonic blood soup for the treatment of abnormal uterine bleeding.GO and KEGG enrichment analyses of the key targets were performed via the Microbiology Letter website.The common targets and active ingredients were docked using Autodock.4 software and the top 6 groups of results with the lowest binding energy were visualised using Pymol software.Resut:Various components in Angelica tonic blood soup such as quercetin,mangostemonin,isorhamnetin,kaempferol,β-sitosterol and dousterol may act on AKT1,MAPK8,ESR1,RELA and other targets to exert therapeutic effects on abnormal uterine bleeding through modulating IL-17 signaling pathway,TNF signaling pathway and endocrine resistance pathway.Result:The database was used to screen 22 active ingredients,208 drug targets and 2847 disease targets of abnormal uterine bleeding.The active ingredients were cross-plotted with disease targets to obtain 150 cross-targets.A PPI network was constructed using the String database to show the potential targets of Angelica tonic blood soup for the treatment of AUB,and target protein interaction data were visualised using Cytoscape 3.8.0 software.A total of 33 targets with greater than 2 times the median Degree value,greater than 2 times the median BetweennessCentrality and greater than the median ClosenessCentrality were identified and visualized in Figure 4.,TNF,FOS,MYC,CAV1,EGFR,IL6,RXRA,VEGFA,AR,HIF1A,MAPK8,RB1,STAT1,CDKN1A,CCND1,NCOA1,IL10,CYP1A1,BCL2L1,CASP3,PRKCA,PPARG,NFKBIA,IL4The above 33 key targets have important roles in the reciprocal network and can be used as important predictive targets for the treatment of AUB with Angelica tonic blood soup.The top 10 active ingredients of Angelica tonic blood soup were selected for molecular docking with the top 6 core targets,and it was found that when TP53 and MAPK1 were docked with the small molecules,the three structures of the large proteins could not be docked with the small molecules.The highest binding energy after docking was-22.22(kj/mol)and the lowest was-37.36(kj/mol),indicating that the active chemical components of Angelica tonic blood soup could bind well to the core targets of AUB.GO analysis and KEGG pathway analysis revealed that the treatment of abnormal uterine bleeding with Angelica tonic blood soup mainly involves biological processes such as drug response,positive regulation of gene expression,response to xenobiotic stimuli,and DNA modules.Molecular functions mainly involved enzyme inactivation,protein function inactivation,positive regulation of RNA polymerase Ⅱ promoter transcription,and upregulation of protease activity.Cellular components involve polymeric complexes such as membrane rafts,transcription factor complexes,mitochondria,and cell membrane cave-like invagination networks.Therapeutic targets are enriched in cancer pathways,lipids and atherosclerosis,AGE-RAGE signalling pathway in diabetic complications,prostate cancer,hepatitis B,herpesvirus infection associated with caspian sarcoma,pancreatic cancer,fluid shear stress and arterial atherosclerosis,cytomegalovirus,IL-17 signalling pathway,chemo-oncogenic receptor activation,TNF signalling pathway,endocrine resistance,etc.Conclusion:Quercetin,mangostemonin,isorhamnetin,kaempferol,β-sitosterol,dousterol and other components in Angelica tonic blood soup may act on AKT1,MAPK8,ESR1,RELA and other targets to exert therapeutic effects on abnormal uterine bleeding by modulating IL-17 signalling pathway,TNF signalling pathway and endocrine resistance.