Study On The Mechanism Of Shaoyao Gancao Decoction In The Treatment Of Restless Leg Syndrome Based On Network Pharmacology

Objective:Through the network pharmacological method,this paper explores the mechanism of Shaoyao Gancao Dcoction(SGD)in the treatment of restless leg syndrome,so as to open up ideas for subsequent experimental research and provide scientific basis for clinical application.Methods:This study applies Traditional Chinese Medicine Database and Analysis Platform System Pharmacology(TCMSP)as well as the literature review,retrieve and collect peony SGD of radix paeoniae alba and radix glycyrrhizae in chemical composition information,with oral bioavailability(OB)and a kind of medicinal property(DL)0.18 or 30% or higher for the standard screening of active ingredients and targets,with the aid of Uni Prot database to standardization of target protein name,build SGD effective component potential targets data set.By collecting and screening disease targets related to restless leg syndrome through Gene Cards database,Disge Net database and CTD database,the target information dataset of active ingredients of SGD was constructed.The Venn graph is used to obtain common targets.The visualized network software Cytoscape 3.7.2 was used to construct the componenttargets-disease network of SGD for the treatment of restless leg syndrome.The high confidence interaction relationships of common target proteins were obtained from the String database,and the protein interaction network(PPI)was constructed in Cytoscape software.Cyto NCA plug-in was applied to perform topological analysis on the network,and the core targets of SGD for the treatment of restless leg syndrome were selected.Metascape database was used for GO enrichment analysis and KEGG pathway enrichment analysis of potential targets and signaling pathways.Results:1.Collection and screening of active ingredients of SGD: 85 compounds of paeony root and 280 compounds of Glycyrrhizae root were retrieved from TCMSP database.A total of105 active ingredients met the conditions of OB≥30% and DL≥0.18,and 102 active ingredients were obtained from the combined drugs,including 13 active ingredients of Paeonia lactiflora and 92 active ingredients of licorice.Sitosterol,kaempferol and Mairin were the common active ingredients of both Paeonia lactiflora and licorice.2.Drug and disease target screening of SGD: 74 action targets of Paeonia lactiflora and125 action targets of Glycyrrhiza were obtained from TCMSP database.Through standardized verification of Uniprot database,the repeated,non-human and non-standard targets were eliminated,and the final potential action targets of active ingredients in SGD were 96.A total of 2172 targets related to restless leg syndrome were screened based on Gene Cards database,Disge Net database and CTD database.There are 68 intersecting targets for drugs and diseases.3.SGD active ingredients-targets-RLS network: SGD active ingredients-target network consists of 232 nodes and 2193 edges.The network topology analysis showed that the median Degree of each compound was 54.5,among which kaempferol(MOL000422)had the highest node Degree and acted on 110 drug targets.Quercetin(MOL000098)was the next most targeted drug with 87 targets.The average degree of each target was 46.5,which was higher than the average value of 21 targets,among which the high degree of estrogen receptor alpha gene(ESR1)targeting 92,androgen receptor(AR)targeting 91,prostaglandin-endoperoxide synthase 2,PTGS2,a proliferative peroxisome proliferative receptor gamma(PPARG),targets 84 of them.4.Protein-protein interaction(PPI)networks: based on the String database feedback intersection of target protein information,the high degree of confidence of interaction in Cytoscape software build SGD in the treatment of restless legs syndrome of PPI network target protein,remove the interaction with other target protein without the free targets,PPI network node,a total of 64 453.The larger the diameter and darker the color of the node,the higher the Degree value of the node,and the more target proteins interacting with it.The thicker and darker the edge,the stronger the interaction between the two target proteins.Cytonca plug-ins were used for topology analysis of the network,and the results showed that the median of Degree was 12,BC median was 0.004562,and CC median was 0.49028.A total of 11 targets met the screening conditions of core targets,mainly including IL6,TP53,TNF,Jun,MAPK1,PTGS2,ESR1,PPARG,AR,HSP90aa1,and MAPK14.Conclusion:1.Through database search,it is found that Shaoyao Gancao Dcoction has a variety of compound components,and the treatment of restless leg syndrome by SGD is a combination of multiple components,among which paeoniflorin,kaanxiol,quercetin and glycyrrhiza may be the core components of Shaoyao Gancao Dcoction in the treatment of restless leg syndrome.2.In the active ingredient target prediction filter peony liquorice decoction,the active ingredient can be applied to multiple targets,IL6,TP53,TNF,JUN,MAPK1,PTGS2,ESR1,PPARG,AR,HSP90AA1,MAPK14 and other targets may be closely related to the active ingredients of Shaoyao Gancao Decoction and restless leg syndrome.3.GO enrichment of biological processes involved in regulating neurotransmitter receptors and kinase activity and protein kinase activity,cell response to nitrogen compounds,cell response to organic cyclic compound,response to toxic substances,cell responses to drugs,chemical synaptic transmission,the circulation of blood,blood vessels,development,MAPK cascade is regulation,active oxygen metabolism,etc.,These biological processes may play a key role in the treatment of RLS by Peony and Glycyrrhizae Decoction.4.KEGG pathway enrichment results cancer involving intervention approach,neural activity ligand receptor interaction,fluid shear stress and atherosclerosis,diabetes complications of AGE-RAGE,PI3 K signal channel-Akt signaling pathways,estrogen signaling pathways,cell aging,including serotonin synapses,nonalcoholic fatty liver disease,myocardial cells And AMPK signaling pathway,suggesting that Peony Glycyrhizoma Decoction may play a role in the treatment of RLS through these pathways.