Systematic Evaluation Of Danbie Capsule In The Adjuvant Treatment Of Hysteromyoma And Its Network Pharmacological Analysis

Objective:To systematically evaluate the efficacy and safety of Danbie capsule combined with mifepristone in the treatment of hysteromyoma,so as to provide scientific basis for its clinical application;To explore the mechanism of Danbie capsule against hysteromyoma based on network pharmacology and bioinformatics.Methods:Pub Med,The Cochrane Library,EMBase,Clinical Trials,CNKI,VIP,Wanfang and Sino Med were searched to collect randomized controlled trials(RCTs)of Danbie capsule combined with mifepristone in the treatment of hysteromyoma from the time of database establishment to February 2022.Two researchers independently screened the literature,extracted the data,and evaluated the risk of literature bias.Meta analysis and experimental sequential analysis were performed by revman5.3 software and TSA v0.9software respectively.According to the screening criteria,the target proteins of the active components of Danbie capsule were searched in TCMSP and TCMID databases,the target protein form was transformed into target gene form by Uni Prot database,the disease genes of hysteromyoma were searched in Gene Cards,Dis Ge NET and Open Targets Platform databases,and the target genes of hysteromyoma in the above three databases were combined and de-duplicated,and the target genes of the active components of Danbie capsule were intersected to obtain the anti hysteromyoma target of the active components of Danbie capsule;With the help of Cytoscape3.7.2 software,the active component anti hysteromyoma target network of Danbie capsule was constructed to screen the key components of Danbie capsule against hysteromyoma.The Protein-protein interaction network and module analysis of target proteins were carried out by using STRING and Metascape database,and the key targets of Danbie capsule against hysteromyoma were excavated.Go biological process and KEGG pathway enrichment analysis of key targets were carried out by using David 6.8 platform.Cytoscape3.7.2 software was used to construct the signal pathway network of the active component of Danbie capsule-the key target of anti hysteromyoma.Finally,the molecular docking between the key active components of Danbie capsule and the key target of hysteromyoma was verified.Results:Fifteen RCTs meeting the inclusion criteria,involving 1359 patients.Meta ana lysis shows that the improvement of total clinical effective rate[RR=1.25,95%CI(1.18,1.33),P<0.00001],reducing the volume of hysteromyoma[SMD=-0.84,95%CI(-1.14,-0.55,P<0.00001],reducing serum follicle stimulating hormone[SMD=-1.78,95% CI(-2.75,-0.81),P=0.0003),estradiol[SMD=-1.27,95%CI(-1.87,-0.66),P<0.0001],Luteinizing hormone[SMD=-1.67,95%CI(-2.47,-0.87),P<0.0001],Progesterone[SMD=-2.10,95%CI(-3.65,-0.56),P=0.008],and syndrome score of qi stagnation and blood stasis syndrome[SM D=-1.15,95%CI(-1.38,-0.92),P<0.00001],etc,the combination of danbie capsule and mifepristone was better than mifepristone alone,with significant statistical difference.After combined with danbie capsule,the incidence of common adverse reactions of mifepristone such as nausea and vomiting[RR=0.68,95%CI(0.35,1.34),P=0.27],fatigue[RR=0.50,95%CI(0.15,1.62),P=0.25],dizziness and headache[RR=0.53,95% CI(0.13,2.14),P=0.37],lower abdominal pain[RR=0.36,95%CI(0.10,1.33),P=0.12] were not significantly increased,And there were no new adverse reactions.Sequential analysis showed that the cumulative Z value of clinical efficacy passed through the traditional and TSA thresholds,which further confirmed the effectiveness of combined Danbie capsule.The 144 active components of 12 traditional Chinese medicines in Danbie capsule could act on 295 targets,and 15 key active components were screened,including quercetin,luteolin,kaempferol,wogonin,β-Sitosterol,baicalein,tanshinone IIA,formononetin,etc,and 30 key targets,including AKT1,ALB,IL6,TP53,VEGFA,TNF,MAPK1,EGFR,CASP3,EGF,MMP9,etc;Involved in cell proliferation,protein signal transduction,protein phosphorylation,angiogenesis,apoptosis and other biological processes;Regulation of TNF,MAPK,estrogen,VEGF and other 20 signaling pathways;The key ingredient quercetin had good affinity with its eight key targets.Conclusion:Danbie capsule combined with mifepristone can significantly improve the total effective rate of hysteromyoma treatment,reduce the tumor size,reduce serum sex hormone levels,improve hemorheology,while it will not increase the inherent adverse reactions of mifepristone and other new adverse reactions.It has definite curative effect and good safety;Danbie capsule is characterized by multi-component,multi-target and multi-pathway cooperation in against hysteromyoma.MOL000098(Quercetin),AKT1 and Pathways in cancer are the best active component,targets and signaling pathways for against hysteromyoma.