Meta Analysis And Network Pharmacology Study Of Dachaihu Decoction For Chronic Cholecystitis

Objective:Based on the research method of Meta analysis,the clinical efficacy and safety of Dachaihu Decoction in the treatment of chronic cholecystitis were systematically evaluated,and the potential targets and mechanism of action of Dachaihu Decoction in the treatment of chronic cholecystitis were further analyzed through the research method of network pharmacology,providing further evidence for clinical application.Methods:1.Randomized clinical trials(RCTS)on the treatment of chronic cholecystitis by Dachaihu Decoction were searched from CNKI,VIP Database,Wanfang Database,Chinese Biomedical Database,Pubmed,Cochrane Library,EMBase and other Chinese and English databases from the establishment of the database to November 30,2021.Qualified literatures were screened based on inclusion and exclusion criteria.After quality assessment using Cochrane bias risk assessment tools,meta-analysis was conducted in Rev Man5.4 and conclusions were drawn.2.Using TCMSP database,the effective active ingredients and their corresponding target proteins in Dachaihu Decoction were obtained,and the corresponding gene names were normalized one by one with Uniprot database,and the drug-component-target network diagram of Dachaihu Decoction was drawn in Cytoscape3.9.0.The disease targets of chronic cholecystitis were retrieved by Gene Cards and OMIM databases using the keyword "chronic cholecystitis".The common targets were obtained by intersection of Venny2.1 software and imported into STRING11.5 database.Protein interaction information was obtained and PPI network map was constructed using Cytoscape3.9.0 software.At the same time,DAVID was used to conduct GO functional enrichment and KEGG pathway enrichment analysis for target proteins obtained from the network.Results:1.A total of 17 literatures were included,including 1870 cases.Meta-analysis results showed that the total clinical response rate of Dachaihu Decoction for chronic cholecystitis[RR=1.22,95%CI(1.17,1.27),P<0.00001].The improvement of TCM syndrome,including pain at right side[MD=-0.45,95%CI(-0.60,-0.29),P<0.00001],dry mouth or mouth bitter [MD=-0.42,95%CI(-0.64,-0.20),P=0.0002<0.05],Poor or dull appetite [MD=-0.65,95%CI(-0.72,-0.58),P<0.00001];Image(B ultrasound)improvement rate [RR=1.22,95%CI(1.10,1.35),P=0.0002<0.05];The recurrence rate[RR=0.19,95%CI(0.08,0.43],P<0.0001] was better than the control group,and the difference was statistically significant.2.A total of 133 active ingredients were obtained,including quercetin,β-sitosterol,stigmasterol and kaempferol.720 targets were predicted,of which76 were intersections with chronic cholecystitis,and the key targets were AKT1,ALB,IL6,TP53,TNF,VEGFA,IL1 B,PTGS2,MAPK3,EGFR,etc.A total of 552 GO items were obtained by GO functional enrichment analysis,including 424 biological processes,45 cell components and 83 molecular functions.KEGG pathway analysis revealed 110 related signaling pathways,which were mainly closely related to HIF-1,PI3K-Akt,tumor necrosis factor,FoxO,MAPK and other signaling pathways.Conclusion:1.The total effective rate of Dachaihu Decoction plus or minus conventional medicine in treating chronic cholecystitis was better than conventional medicine alone.2.Dachaihu Decoction plus or minus or combined with conventional drug therapy was superior to conventional drug therapy in improving right hypochondriac pain,dry mouth and bitter mouth,poor or dull appetite,improvement rate of imaging(B ultrasound)and recurrence rate.3.Dachaihu Decoction plus or minus or combined with conventional drugs in the treatment of chronic cholecystitis has few adverse reactions and high safety.4.Dachaihu Decoction mainly regulates AKT1,ALB,IL6,TP53,TNF,VEGFA,IL1 B,PTGS2,MAPK3,EGFR and other key targets,and acts on HIF-1,PI3K-Akt,tumor necrosis factor,FoxO,MAPK and other signaling pathways.Inhibit the occurrence and development of inflammatory response,reduce cell damage,and promote the recovery of the disease.