Mechanism Study of Triphala Regulating Pancreatic Islet β Cell Function Based on Network Pharmacology and Experimental Verification
Objective To explore the active components and potential molecular mechanism of Triphala (composed of Phyllanthi Fructus,Terminaliae Belliricae Fructus and Chebulae Fructus,THL) in regulating the function of pancreatic islet β by using the network pharmacology method and animal experiment verification. Methods The active constituents and predicted targets of THL were obtained by Traditional Chinese Medicine Database and Analysis Platform (TCMSP)combined with literature search and SwissADME. The main targets of diabetes were obtained from Drugbank,Genecards,OMIM and TTD databases. Venn diagram was used to analyze the common genes of drugs and disease,and STRING database and CytoScape 3.8.0 software was used to construct the protein-protein interaction(PPI)network of the common targets of "THL-compositions-targets-genes-disease." The potential targets and their enrichment pathways were visualized using ClueGO and CytoHubba. Wistar male rats were randomly divided into normal group,model group and low-,medium-and high-dose (0.43,0.86,1.72 g·kg-1) THL groups. The diabetic model was replicated by introperitoneally injecting streptozotocin (STZ). The followup experiment was carried out with corresponding drug. Pancreatic islet function index calculation,pathological section staining,and PCR detection were then carried out. Results There were 23 active ingredients in THL,434 predicted targets,1200 disease genes. A total of 146 common genes in THL and diabetes were obtained by Venn analysis. It was found that THL in the treatment of diabetes was mainly related to regulating insulin secretion,glucose transmembrane transport,activation of protein kinase,promoting vascular growth and MAPK cascade reaction,which were involved seven core targets including protein kinase B alpha(AKT1),glyceraldehyde-3-phosphate glyceraldehyde dehydrogenase(GAPDH),vascular endothelial growth factor A (VEGFA),mitogen activated protein kinase 1 (MAPK1),prostaglandin endoperoxide synthase (PTGS2),signal transduction and transcription activating factor 3 (STAT3),and Toll-like receptor 4 (TLR4). Animal validation results showed that THL could increase HOMA-β index (P<0.01),promote recovery of pancreatic islet volume and β cell function,decrease the number of α cell,and significantly up-regulate the expression of AKT1 and GAPDH genes in rat pancreatic tissue(P<0.001),as well as down-regulate the expression of VEGFA,MAPK1,PTGS2,STAT3,and TLR4 genes(P<0.001,P<0.0001). The partial prediction of network pharmacology results were validated with the experimental results. Conclusion THL can treat diabetes through multiple targets and pathways. It is confirmed that THL could achieve the effect of treating diabetes by regulating seven key target genes including AKT1,GAPDH,VEGFA,MAPK1,PTGS2,STAT3 and TLR4 to regulate the function of pancreatic islet β cells. This study can provide a reliable basis for the clinical use and basic research of THL in anti-diabetes.
万方数据
维普
