Study On The Effectiveness And Molecular Mechanism Of Daxianxiong Decoction In Treating Acute Pancreatitis

Objective: Acute pancreatitis(AP)is a relatively common inflammatory disease,and its treatment mechanism is still unclear.Daxianxiong decoction(DXXD)is a drug for relieving AP,which has a wide range of clinical applications.Therefore,it is particularly important to study its mechanism of action in the treatment of AP.This paper first explores the clinical effectiveness of DXXD in treating AP through meta analysis,then explores the mechanism through network pharmacology,molecular docking and molecular dynamics simulation.Finally,it was verified by cell experiments in vitro.Method: Randomized controlled trials(RCTs)of DXXD in the treatment of AP were collected from CNKI,Wan Fang Data,VIP,Chinese Database of Biomedical Literature(CBM),Pub Med,Embase,Cochrane library and other databases.Rev Man 5.3 software was used for bias risk analysis,and the result indicators were analyzed.Traditional Chinese medicine ingredients of DXXD were obtained through ETCM database and data,and then the targets of traditional Chinese medicine ingredients were predicted by Swiss target prediction platform.Associated AP targets were obtained by combining Pharm GKB,NCBI,OMIM and Gene Cards databases.Venny 2.1.0 platform was used to obtain potential targets of DXXD for AP treatment,and STRING database was used for protein PPI interaction analysis to obtain key targets of DXXD for AP treatment.The network of“DXXD-traditional Chinese medicine ingredients-potential target-AP” was constructed through Cytoscape 3.8.0 software to obtain the key traditional Chinese medicine ingredients of DXXD for AP treatment.Metascape database was used for GO and KEGG enrichment analysis.Auto Dock Tools 1.5.7 and Auto Dock Vina 1.1.2 were used for molecular docking of key traditional Chinese medicine ingredients and key action targets,and Amber 16 software was used for molecular dynamics simulation of complexes with low molecular docking energy.Finally,the primary pancreatic acinar cells of mice were extracted to study the protective effect of DXXD on the necrosis of pancreatic acinar cells induced by sodium taurocholate(Na T),and the expression of key pathway target protein was detected by western blot.Result: A total of 9 RCTs were included in the meta analysis,involving a total of 716 patients,including 390 in the test group and 326 in the control group.Through the analysis,it was found that the risk of bias included in the study was not high.The results of meta analysis showed that the total effective rate of the treatment group was higher than that of the control group,Z=4.25(P<0.0001),and there was no heterogeneity among the study groups.The abdominal pain relief time in the treatment group was shorter than that in the control group,Z=7.25(P<0.00001),sensitivity analysis to find the source of heterogeneity.The first defecation time in the treatment group was shorter than that in the control group,Z=7.68(P<0.00001),and there was no heterogeneity among the study groups.The rebound pain recovery time in the treatment group was shorter than that in the control group,Z=7.81(P<0.0001),and there was no heterogeneity among the study groups.The bowel sound recovery time in the treatment group was shorter than that in the control group,Z=2.68(P=0.007),and the source of heterogeneity was found by sensitivity analysis.Complication rate in the treatment group was lower than that in the control group,Z=3.29(P=0.001),and there was no heterogeneity among the study groups.A total of 24 kinds of traditional Chinese medicine ingredients were obtained,including 536 targets,681 AP targets and 95 potential therapeutic targets.The key therapeutic targets were STAT3,IL6,AKT1,TNF,and IL1 B,and the key traditional Chinese medicine ingredients were emodin,rhein,chrysophanol,physcion,and euphadienol.GO functional enrichment analysis mainly involved the regulation of secretion,apoptosis signaling pathway,and autophagy.The enrichment analysis of KEGG pathway mainly involved PI3K-Akt signaling pathway and JAK-STAT signaling pathway.Through molecular docking and molecular dynamics,it was found that the key ingredients of traditional Chinese medicine could combine with the key targets stably and have strong affinity.The experiment showed that DXXD could protect the pancreatic acinar cell necrosis induced by Na T,and the western blot experiment showed that DXXD could reduce the expression of AKT,STAT3,p-AKT,p-STAT3.Conclusion: This paper first studys the effectiveness of DXXD in treating acute pancreatitis through meta analysis,and predicts the mechanism of DXXD in treating acute pancreatitis by using network pharmacology,molecular docking and molecular dynamics simulation,indicating that DXXD achieves the effect of treating acute pancreatitis through multi-ingredients,multi-targets and multi-pathways.In vitro experiments have verified the relevant targets obtained from network pharmacology and the protective effect on pancreatic acinar cells.