The Mechanism Study About Shexiang Baoxin Pill In Treating Coronary Microcirculation Disease Based On Network Pharmology

Objective: The effective components and possible targets of Shexiang Baoxin Pill in the treatment of Coronary microcirculation disease(CMD)were studied by using network pharmacology technology and Cytoscape visualization software,and the possible mechanism of Shexiang Baoxin Pill in the treatment of CMD was discussed.Methods : Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform TCMSP)obtained the active components and targets of panax ginseng,bezoar,borneol,storax and cinnamon with OB≥30% and DL≥0.1.In addition,gene symbol transformation was carried out on the collected targets through Uni Prot.The Traditional Chinese Medicine Integrated Database(TCMID)was used to search the chemical components of two Chinese medicines,musk and Toad venom,which were not found in TCMSP.Then Swiss Target Prediction was used to predict the Target proteins of related compounds,and the repeated values and targets of non-human origin were removed.OMIM database and Gene Cards database were used to predict CMD disease targets,and the intersection genes of Shexiang Baoxin Pill compound target and CMD disease target were constructed.Cytoscape3.6.0 was used to construct active componenttarget-disease network diagram of Shexiang Baoxin Pill.PPI network was constructed by String database and topology analysis was conducted to obtain the core targets of Shexiang Baoxin Pill and CMD.GO analysis and KEGG pathway enrichment analysis were conducted on the core targets by DAVID database,and the possible synergistic mechanism of multi-gene,multi-target and multi-pathway of Shexiang Baoxin Pill in the treatment of coronary microcirculation diseases was obtained.Results:1.Collection and screening of active ingredients in Shexiang Baoxin Pills: There were 84 active ingredients and 678 targets in Shexiang Baoxin Pills,including 31 components and 306 targets in ginseng;Musk has 20 components and 107 targets.Toad venom contains 8 components and 54 targets.Cinnamon has 10 components and 122 targets.5 components and 17 targets of bezoar;Borneol consisted of 1 component and 10 targets;Borneol consisted of 1component and 10 targets.2.A total of 1778 targets related to CMD were screened from Gene Cards database and OMIM database,among which 115 were intersection targets of the two databases.There were 71 mapping targets between Shexiang Baoxin Pill and CMD.3.PPI Network Analysis: The PPI network diagram of 71 intersection targets was constructed through String database,and the confidence was adjusted to 0.4.In the topology analysis results,there were 15 targets with Degree value ≥35.These targets involve induction of apoptosis,inflammatory response,immune response,oxidative stress,lipid metabolism and angiogenesis,oxygen free radical generation,fibrinolysis,insulin resistance,thrombosis,atherosclerosis and so on.4.GO enrichment analysis and KEGG pathway enrichment analysis: By biological process,according to the analysis of target genes and molecular mainly involved in the biosynthesis of nitric oxide process regulation,cytokine mediated signaling pathways,cellular response to organic cyclics,response to lipopolysaccharide and external stimulation,the regulation of gene expression,regulation and control of are 1-single oxygenase activated calcium diol,cell response to hypoxia.Cellular Component(CC)analysis revealed that these activities mainly occurred in extracellular matrix,cytoplasm and endoplasmic reticulum.Molecular Function(MF)analysis showed that the target was mainly involved in regulating protein binding,enzyme binding activity and cytokine activity.KEGG analysis suggested that these genes may regulate the occurrence of disease by activating or inhibiting fluid shear stress and atherosclerosis,the role of age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,lipid and atherosclerosis,and IL-17 signaling pathway.Conclusions: The results of network pharmacology suggest that the possible mechanism of Shexiang Baoxin Pill in treating CMD may involve:(1)By increasing the phosphorylation of nitric oxide synthase(e NOS)in endothelial cells,promote the release of NO and improve the microvascular relaxation function;(2)Inhibit the release of chemokines and inflammatory factors produced by endothelial cells due to low shear stress,reduce the inflammatory response,and improve microvascular endothelial function;(3)Inhibition of DDP4 incretin system through AGE-RAGE pathway may reduce postprandial hyperglycemia,which is a risk factor of coronary microcirculation disease,and thus has cardiac protective effect;(4)By inhibiting the release of tumor necrosis factor,the inflammatory response caused by oxidative stress can be reduced,and the myocardial injury caused by microvascular disorders can be alleviated.