Study On The Mechanism Of Jiawei Chaihu Shugan Decoction In The Treatment Of Epilepsy Based On Network Pharmacology

Objective: To explore the main active ingredients,core therapeutic targets and key signaling pathways of Jiawei Chaihu Shugan decoction for the treatment of epilepsy through network pharmacology techniques.Then explore the possible mechanism of action of Jiawei Chaihu Shugan decoction for the treatment of epilepsy.Methods: Firstly,the targets related to epilepsy were collected and integrated from Dis Ge NET,OMIM,Therapeutic Target Database,Pharm Gkb and Gene Cards databases.The active ingredients and targets in Jiawei Chaihu Shugan decoction were searched in TCMSP database.Then the online software Venny was used to analysis the potential target of Jiawei Chaihu Shugan decoction in the treatment of epilepsy.At the same time,Cytoscape software was used to construct the "ingredients-targets" relational network.Secondly,the functional analysis of potential targets was carried out,and the "PPI" relational network was constructed by STRING database,and the core sub-network was constructed by Cyto NCA plug-in in Cytoscape software.Meanwhile,the cluster Profiler package in R software was used to carry out the gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis for potential targets.Then the "targets-KEGG pathways" relationship network was constructed by Cytoscape software.Results: There were 155 active ingredients of Jiawei Chaihu Shugan decoction in this study,mainly including beta-sitosterol,kaempferol,quercetin,luteolin,naringenin,Peimisine,pelargonidin,Rhynchophylline,paeoniflorin,isorhamnetin,Hesperetin,Myricanone and formononetin.There are 246 targets for the action of the active ingredients of Jiawei Chaihu Shugan decoction.A total of 4580 epilepsy-related targets were collected and integrated from Dis Ge NET,OMIM,Therapeutic Target Database,Pharm Gkb,and Gene Cards databases.There are 147 potential targets for epilepsy treatment were obtained by mapping through Venny.All of these 147 potential targets have direct or indirect relationships with each other.The analysis of the PPI core sub-network can yield 22 core targets,namely MAPK3,MAPK14,CCND1,AKT1,IL1 B,CCL2,MMP2,MAPK1,EGF,EGFR,MYC,TP53,ESR1,CXCL8,MAPK8,MMP9,VEGFA,PTGS2,CASP3,FOS,STAT3,and TNF.The biological functions affected by the potential targets of Jiawei Chaihu Shugan decoction in the treatment of epilepsy include: response to metal ion,response to reactive oxygen species,response to oxidative stress,integral component of presynaptic membrane,intrinsic component of postsynaptic membrane,intrinsic component of presynaptic membrane,integral component of synaptic membrane,intrinsic component of synaptic membrane,presynaptic membrane,catecholamine binding,neurotransmitter receptor activity,protease binding,protein-coupled amine receptor activity,cytokine receptor binding,dopamine binding,etc.The main KEGG signaling pathways involved include apoptosis,Fluid shear stress and atherosclerosis,TNF signaling pathway,IL-17 signaling pathway,VEGF signaling pathway and Prolactin signaling pathway.By jointly analyzing the "targets-KEGG pathways" relationship network,PPI core sub-network and apoptosis pathway,we further screened 8 core targets including AKT1,TP53,TNF,MAPK1,MAPK8,MAPK3,FOS and CASP3.These eight core targets are not only the key targets in the PPI core sub-network,but also the important targets in the KEGG relationship network,as well as the core targets enriched in the apoptotic pathway.Conclusion: Through the network pharmacology research,we hypothesized that the beta-sitosterol,kaempferol,quercetin,luteolin,naringenin,Peimisine,pelargonidin,Rhynchophylline,paeoniflorin,isorhamnetin,Hesperetin,Myricanone,formononetin and other active ingredients of Jiawei Chaihu Shugan decoction may affect the biological functions of response to reactive oxygen species,response to oxidative stress,presynaptic membrane,catecholamine binding,neurotransmitter receptor activity,dopamine binding and so on.and regulate the signal pathway such as apoptosis,Fluid shear stress and atherosclerosis,TNF signaling pathway,IL-17 signaling pathway,VEGF signaling pathway,Prolactin signaling pathway,Then play an anti-epilepsy role by targeting the core targets like AKT1,TP53,TNF,mapk1,mapk8,mapk3,FOS and CASP3.