Network Pharmacology Study Of Tongqiao Huoxue Decoction In The Treatment Of Vascular Dementia

ObjectiveBased on network pharmacology,the potential pharmacodynamics,core compatibility and biological mechanism of tongqiaohuoxue decoction in the treatment of VD were studied.Methods(1)All the compounds in tongqaohuoxue decoction were obtained by searching TCMSP and TCMID,and the adme-tox was evaluated and screened by faf-drugs4 database,and compounds with good drug properties were selected as potential pharmacophones.The intestinal absorption capacity and blood-brain barrier permeability of potential pharmacophones in tongqaohuoxue decoction were evaluated by SwissADME website(2)TCMSP and SwissTargetPrediction were used to obtain the potential therapeutic targets of tongqaohuoxuoxu decoction,and GeneCard,OMIM and DisGeNET disease databases were used to obtain the targets related to vascular dementia.The potential pharmacodynamic targets were matched with disease-related targets to obtain potential pharmacodynamic molecular-disease action targets,and the potential pharmacodynamic molecular-action targets and drug-target-disease networks were constructed.The prediction of potential pharmacodynamic substances and the core compatibility of tongqiaohuoxue decoction in the treatment of VD were studied.(3)Cytoscape3.7.1 software BisoGenet plug-in was used to construct the PPI network of potential pharmacodynamic molecuer-disease targets,and CytoNCA plug-in was used to conduct topological analysis of the targets in the PPI network to obtain the core network targets.DAVIAD database was used to conduct GO enrichment analysis and KEGG pathway enrichment analysis for core network targets,and the biological significance of core network targets and possible signaling pathways were preliminarily analyzed and explored,so as to analyze the biological mechanism of tongqiaohuoxue decoction in the treatment of VD.Results(1)After the screening of adme-tox parameters of all pharmaceutical ingredients in tongqiaohuoxue decoction,30 potential pharmacodynamic molecules of musk,18 potential pharmacodynamic molecules of peach kernel,58 potential pharmacodynamic molecules of safflower,90 potential pharmacodynamic molecules of ligusticum wallichii,32 potential pharmacodynamic molecules of red peony root,116 potential pharmacodynamic molecules of ginger,28 potential pharmacodynamic molecules of jujube and 43 potential pharmacodynamic molecules of scallion were obtained,respectively.SwissADME evaluation showed that tongqiaohuoxue decoction had good intestinal absorption capacity and blood-brain barrier permeability,among which safflower,chuanxiong,red peony root and jujube were more inclined to intestinal absorption,while musk,ginger and scallion had better intestinal absorption capacity and blood-brain barrier permeability.(2)After matching drug targets with disease targets,a total of 285 potential pharmacodynamic molecular-disease targets were obtained.Among them,there were 104 musk targets(36.5%of all targets)and 71 scallion targets(24.9%of all targets)in the tongqiao group,and a total of 19 musk-scallion targets.In the promoting blood circulation group,there were 166 targets of safflower action(accounting for 58.2%of all targets),87 targets of red peony root action(accounting for 30.5%of all targets),64 targets of ligusticum wallichii action(accounting for 22.5%of all targets),and 28 targets of peach seed action(accounting for 9.8%of all targets).There were 149 action targets of jujube(52.3%of all targets)and 90 action targets of ginger(31.6%of all targets)in the Harmonizing Ying-qi and Wei-qi group.(3)Through the construction and analysis of the potential pharmacodynamic molecules-action target network,it was found that the main potential pharmacodynamic molecules in the tongqiao group for the treatment of VD were:kaempferol,paeonol,butylated hydroxyioluene,testosterone,syringine,etc.The main potential pharmacodynamic molecules in the promoting blood circulation group for the treatment of VD were quercetin,baicalein,apigenin,caffeic acid,kaempferol,luteolin,etc.The main potential pharmacodynamic molecules in the Harmonizing Ying-qi and Wei-qi group for the treatment of VD were quercetin,eugenol,6-gingerol,Nuciferin,tepharine and isoeugenol,etc(4)Through the construction and analysis of PPI network,it was found that the treatment of VD by tong qiaohuoxue decoction has the synergistic effect of multiple components and targets,among which the target proteins such as APP,NTRK1,CUL3,EGFR,XPO1,TP53,MCM2,ESR1,UBC and FN1 may be the core targets for the treatment of VD by tong qiaohuoxue decoction.GO analysis showed that toniqo-huosu decoction may play a role in treating VD by regulating telomere tissue,nucleosomal assembly dependent on DNA replication,chromatin silencing of rDNA,heterotestamentation of proteins,initiation of translation,viral transcription,rRNA processing,telomere capping and other biological processes.KEGG pathway analysis indicated that tongqiaohuo xue tang may exert anti-dementia effects by affecting MAPK signaling pathway,tumor necrosis factor signaling pathway,pi3k-akt signaling pathway,mTOR signaling pathway,nf-kb signaling pathway,insulin signaling pathway and cAMP signaling pathway.Conclusion(1)the main pharmacodynamic substances of tongqiaohuoxue decoction in the treatment of VD may be quercetin,kaempferol,paeonol,testosterone,baicalein,aperitin,caffeic acid,luteolin,eugenol,6-gingerol,etc.,and the above ingredients have been proved to have anti-dementia effects,providing a certain basis for the development of clinical VD drugs(2)The core compatibility combination of tongqiaohuoxue decoction in the treatment of VD may be musk-safflower-jujube,which provides certain reference for clinical application of tongqiaohuoxue decoction or tongqiaohuoxue therapy in the treatment of VD.(3)Tongqiaohuoxu decoction in the treatment of VD with multiple targets,multiple way the role of the characteristics of its biological mechanism of dementia and MAPK signal pathway tumor necrosis factor signaling pathways,PI3K-Akt signaling pathways,mTOR signaling pathways,NF-?B signaling pathways,insulin signaling pathway,cAMP signaling pathways and so on,provides clinical application:huoxue decoction in the treatment of VD with modern biological theory foundation,also provide the basis for the next step research and direction.