Network Pharmacology Study Of Gubenzenggu Decoction In The Treatment Of Osteoporosis

Objective:Based on the main active components of Gubenzenggu decoction in the prevention and treatment of osteoporosis by big data mining,the network pharmacology was used to construct the “drug-disease-target-signaling pathway” network and explore its potential mechanism and molecular pathway in the treatment of osteoporosis.Methods:The effective active components of Astragalus,Angelica,Codonopsis,Epimedum,Rehmannia glutinosa,Cistanche deserticola,and Lindera Radix were selected by TCMSP online analysis platform using “OB?30%,DL?0.18,and HL?4.00” as conditions in Guben Zenggu decoction,the disease targets were selected using human gene database(GeneCards)and human Mendelian database(OMIM),and the “disease-TCM compound-target” regulatory network was constructed using Cytoscape 3.7.2 software.Use String software to build a crosstarget protein interaction network and bar graph to analyze protein interactions and core targets.The cluster profiler R package was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on common targets to obtain biological functions and signaling pathways related to the core genes of Gubenzenggu decoction in the treatment of osteoporosis.In the BATMAN-TCM database,“Score cutoff?30,P-value?0.05” is used as the condition to select the active ingredients and targets of the aspirin Astragalus,Angelica,Rehmannia glutinosa,Epimedium,and the same method as above Network pharmacological analysis to predict the possible biological processes and related signal pathways of the two groups of drugs of “Astragalus-Epimedium” and “Angelica-Rehmannia glutinosa” in treating osteoporosis.Result:1.There were 57 core compounds of Gubenzenggu decoction retrieved from TCMSP platform,including digitoflavone,8-isopentenylphenol,sorbitol,mistletoe,?-sitosterol,suzilactone,formonononetin,stigmasterol,luteolin,anhydrokeratin,cadherin,arachidonate,isoflavone,chrysanthin,eugenol,etc.There were 209 predicted targets of active components.After constructing the “compound-active component-disease-target” network,it was found that Gubenzenggu decoction was closely related to AKT1,IL6,VEGFA,UN,PTGS2,CASP3,MAPK1,MAPK8,CXCL8,MMP9,EGF,EGFR,MYC,IL1 B and other target genes in thetreatment of osteoporosis.The results of GO functional enrichment analysis and KEGG pathway enrichment analysis showed that there were 150 GO functions and 148 signaling pathways that may be involved in the treatment of OP with Gubenzenggu decoction.2.Twenty-six active compounds of “Astragalus-Epimedium” were retrieved from the BATMAN-TCM platform,including astragaloside Vi,choline,uridine,astragaloside li,lupeol,stearin,daidzein 1,linoleyl acetate,astragaloside I,?-sitosterol,epimerine,betaine,coracosaponin A,daidzein B,and astragaloside V,and 198 predicted targets.After constructing the “disease-drug pair-compound-target” network,it was found that“Astragalus-Herba Epimedii” drug was closely related to target genes such as ALB,CREB1,NOS3,PTGS2,TNF,DRD2,ESR1,and NR3C1 for the treatment of osteoporosis.The results of GO functional enrichment analysis and KEGG pathway enrichment analysis showed that98 GO functions and 27 signaling pathways may be involved in the treatment of OP with“Astragalus-Epimedium”.3.Seventy-seven active compounds of “Angelica-Rehmannia glutinosa” were retrieved from the BATMAN-TCM platform,including tetradecane,carvacrol,2',4'-dihydroxyacetophenone,uridine,?-elemene,nonanedioic acid,stigmasterol,vitamin B12,vitamin B1,2-methyl-dodecan-5-one,adenine,and choline,and 468 compound predicted targets.After constructing the“disease-drug-compound-target” network,it was found that “Angelica sinensis-Rehmannia glutinosa” drug pair for the treatment of osteoporosis was closely related to target genes such as AKT1,TP53,CREB1,TNF,F2,IL1 B,PPARG,PTGS2,AGT,CAT,ESR1,COMT,and JUN.The results of GO functional enrichment and KEGG pathway enrichment analysis showed 187 possible GO functions and 75 signaling pathways involved in the treatment of OP with “Angelica-Rehmannia glutinosa”.Conclusion:1.Gubenzenggu decoction has the regulation of multimolecular,multiple targets and multiple pathways in the treatment of osteoporosis,which is related to the sympathetic and combined effects between multiple active components of blood entry.2.AKT1,IL6,VEGFA,UN,PTGS2,CASP3,MAPK1,MAPK8,CXCL8,MMP9,EGF,EGFR,MYC,IL1 B belong to the core target genes of Gubenzenggu decoction in the treatment of OP,and the above targets may be involved in nuclear receptor activity,transcription factor activity,steroid hormone receptor activity,cell growth factor activity,RNA polymerase regulation,DNA binding transcriptional activation,redox response,protease hydrolysis activity,ligand receptor binding,signal transduction and other processes to exert biological effects,involving AGE-RAGE,fluid shear stress and atherosclerosis,IL-17,prostate cancer,TNF,hepatitis B and other signaling pathways of diabetic complications.3.The therapeutic effect of “Astragalus-Epimedium” on OP is closely related to ALB,CREB1,NOS3,PTGS2,TNF and other core target genes,which may be involved in some processes of enzyme activity,steroid binding,ammonium ion binding,neurotransmitter binding,G protein-coupled amine receptor activity,heme binding,cofactor binding,tetrapyrrole binding,carboxylic acid binding,organic acid binding,cAMP binding,amine binding,serotonin binding,steroid hormone receptor activity,G protein-coupled serotonin receptor activity and other processes in the body to exert biological effects,mainly involving cAMP,neuroactive ligand-receptor interaction,cGMP-PKG,circadian rhythm,calcium and other signaling pathways.4.“The core target genes of “Angelica-Rehmannia glutinosa”for the treatment of OP are AKT1,TP53,CREB1,TNF,F2,IL1 B,PPARG,PTGS2,and AGT,which may exert effects by regulating biological processes such as steroid hormone receptor activity,nuclear receptor activity,transcription factor activity,oxidoreductase,G-protein-coupled amine receptor activity,ion-gated channel activity,passive transmembrane transporter activity,organic acid binding,and cofactor binding,mainly involving cAMP,cGMP-PKG,calcium,fluid shear stress and signaling pathways such as atherosclerosis and steroids.