酸枣仁-五味子药对抗焦虑药效及网络药理学机制分析研究OACSTPCD

Objective:To clarify the anti-anxiety efficacy of Suanzaoren-Wuweizi(S-W)in a rat model with restraint stress combining with isolation(RS),and to predict the action targets and signaling pathways of S-W on anxiety disorder after compatibility.Methods:The pharmacodynamics of S-W before and after compatibility in the treatment of anxiety was evaluated by open-field test(OFT)and elevated plus-maze test(EPM)in RS model rats of the following groups:control group,model group,positive drug group,Suanzaoren(SZR)group,Wuweizi(WWZ)group,and S-W group.The contents of neurotransmitter and brain-derived neurotrophic factor(BDNF)in rat brain were measured.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database and literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi.The SwissTargetPrediction platform was used to predict drug-related targets,and the GeneCards,TTD,DisGeNET and OMIM database were used to obtain potential targets for the treatment of anxiety with the chemical components of Suanzaoren and Wuweizi.Drug-disease intersection genes were selected and protein-protein interaction(PPI)network was constructed using STRING,and the core targets of S-W after compatibility in the treatment of anxiety were selected according to the topological parameters.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways enrichment analysis were performed via DAVID.The relationship network of"drug-active ingredient-disease-target-pathway"was constructed through Cytoscape 3.8.0.Results:The pharmacodynamics experiment showed that the model group had anxiety as compared with the control group.Compared with the model group,RS rats treated with S-W exhibited significantly increased the number of entries and stay time in the central area of the open field(P<0.05)and significantly increased the percentage of open arm entries(P<0.01).S-W significantly reduced the content of 5-hydroxytryptamine(5-HT)(P<0.05),and significantly increased the levels of dopamine(DA)(P<0.05)as well as BDNF(P<0.01)in the brain of RS model rats.However,the contents of gamma-aminobutyric acid(GABA),glutamate(Glu),Glu/GABA,corticotropin-releasing hormone(CRH)and corticosterone(CORT)were not significantly affected.The results of network pharmacology showed that there were 13 active ingredients in S-W,including sanjoinenine,swertisin,daucosterol,schizandrer B,wuweizisu C and gomisin-A,and 148 potential targets,such as Akt serine/threonine kinase 1(Akt1),tumor necrosis factor(TNF),sodium-dependent 5-HT transporter protein(SLC6A4),and sodium-dependent dopamine transporter protein(SLC6A3).The main pathways involved included neurotransmitter ligand-receptor interaction pathway,serotonergic synapse pathway,cAMP and cGMP-PKG signaling pathways,and also the pathways related to hormone regulation,such as estrogen signaling pathway,gonadotropin secretion pathway and prolactin signaling pathway.Conclusion:S-W has significant anti-anxiety effect after compatibility.Its anti-anxiety mechanism is closely related to the regulation of 5-HT,DA and BDNF contents and multiple signaling pathways.This study provided theoretical and experimental basis for the clinical application of S-W.