Discussion On The Mechanism Of Bushen Zhichan Decoction In The Treatment Of Parkinson’s Disease Based On Network Pharmacology

Objective: To screen out the main active components and their potential targets of Bushen Zhichan Decoction in the treatment of Parkinson’s disease(PD)by network pharmacology method,and to construct the traditional Chinese medicine component-target-disease network by relevant software,so as to further explore the mechanism of Bushen Zhichan Decoction in the treatment of PD.Methods: The effective components and potential targets of Bushen Zhichan Decoction were screened by using the Traditional Chinese Medicine System Pharmacology Technology Platform(TCMSP)and the bioinformatics analysis tool of molecular mechanism of traditional Chinese medicine(BATMA-TCM),and the relevant literature was also searched for supplement.The targets related to PD were searched by human Gene database(Genecard)and online Mendelian Inheritance in Man database(OMIM).The PPI protein interaction network was constructed by STRING database,and the traditional Chinese medicine component-disease-target network was constructed by Cytoscape3.9.1 software.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of Bushen Zhichan Decoction were enriched and analyzed by R language software running the relevant scripts of Shengxin self-learning network,and the KEGG pathway relationship network was finally constructed.Results:(1)Effective ingredients of traditional Chinese medicine: By using TCMSP,the active ingredients of 8 Chinese herbs were found,namely codonopsis codonopsis,wolfberry,Paeoniae paeoniae,unguaria,Cornus officinalis,Fructus xanthii and cistanche.A total of 128 effective ingredients were screened according to the conditions of "oral bioavailability(OB)≥30%,drug similarity(DL)≥0.18".There were 17 codonopsis,36 wolfberry,8 paeoniae paeoniae,6 sesame seed,32 unguteng,14 cornus officinalis,9 Fructus flavus and 6 cistanche deserticola.Since the TCMSP database did not include ejiao,deerhorn gum,ophiopogon ophiopogon,raw turtle shell,raw tortoise board,gastrodia elata and prepared licorice,on the one hand,with "Score≥20,P-value < 0.05" as the screening criteria,drug ingredients and targets were queried from BATMAN-TCM.On the other hand,through the search of literature and the websites of Huayuan.com,Swiss Target Prediction and Swiss ADME,3 ejiao,19 deer horn gum,18 ophiopogon ophiopogon,14 raw turtle shell,7 raw earth,7 raw turtle plate,14 Gastrodia elata and 9 processed glycyrrhiza were finally screened out.A total of 219 effective ingredients were screened.(2)Core targets: STAT3,SRC,MAPK3,MAPK1,HSP90AA1,AKT1,etc.They are likely to be the core targets of Bushen Zhichan Decoction in the treatment of PD.(3)GO enrichment analysis:include 3491 biological processes(BP),215 cell components(CC),353 molecular functions(MF)items.BP involves the response to peptide,antioxidant reaction,cell response to chemical stress,response to foreign biological stimuli,cell response to oxidative stress,response to reactive oxygen species,etc.CC involves membrane raft,membrane microregion,neuron body,cyst cavity,cytoplasmic vesicle cavity,secretory granulocyte cavity,etc.MF involves organic acid binding,tetrapyrrole binding,scaffold protein binding,heme binding,flavonoid adenine dinucleotide binding,carboxylic acid binding,etc.(4)Enrichment analysis of KEGG pathway: The results included 198 pathways,mainly involving AGE-RAGE,atherosclerosis,IL-17,TNF,HIF-1,MAPA and other signaling pathways.Conclusion: The network pharmacology study found that Bushen Zhichan Decoction was likely to act on STAT3,SRC,MAPK3,MAPK1,HSP90AA1,AKT1 and other core genes through stigmasterol,β-sitosterol,sitosterol,quercetin,kaempferol,paeoniflorin,baicalein and other core components.It plays biological functions such as organic acid binding,tetrapyrrole binding,and scaffold protein binding,and finally regulates the signaling pathways such as AGE-RAGE,atherosclerosis,IL-17,TNF,HIF-1,and MAPA to achieve the treatment of PD.