Experimental Study on Anti-Depression of Shuxin Anshen(舒心安神)Decoction Based on Network Pharmacology
Objective:To investigate the effect and mechanism of Shuxin Anshen(舒心安神)Decoction in treating depression through network pharmacology,molecular docking,and animal experiments.Methods:Active components and action targets of Shuxin Anshen Decoction were identified using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Swiss Target Prediction,and Uniprot,and depression-related disease targets were obtained from GeneCards,Online Mendelian Inheritance in Man(OMIM),and Drug-Bank.A visual network was constructed with Cytoscape,and common drug-disease targets were identified using Venny 2.1.These common targets were then entered into the String to generate a protein-protein interaction(PPI)network and to identify key targets.GO enrichment and KEGG pathway analyses of the intersected genes were performed in the Database for Annotation,Visualization and Integrated Discovery(DAVID).Core targets were subjected to molecular docking verification on the CB-Dock online platform,and LC-MS was used to determine the main chemical components of Shuxin Anshen Decoction.A corticosterone-induced mouse model of depression was created,and behavioral tests,Nissl staining,and Western blotting were performed to evaluate the efficacy of Shuxin Anshen Decoction.The levels of brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB),and cAMP-response element binding protein(CREB)were examined.Re-sults Network pharmacology predicted 141 potential active components of Shuxin Anshen Decoction for treating depression,including querce-tin,β-sitosterol,kaempferol,paeoniflorin,monoside,spinosin,and gingerol,and the key targets identified were IL6,ESR1,AKT1,EGFR,etc.GO enrichment analysis found that the depression response was linked to protein phosphorylation,extracellular matrix binding,and protein ki-nase activity.KEGG pathway analysis suggested that Shuxin Anshen Decoction acted through the PI3K-Akt,HIF-1,and MAPK signaling pathways.Molecular docking revealed strong binding affinities between paeoniflorin,monoside,spinosin,gingerol,and targets such as ESR1,AKT1,and BDNF.LC-MS identified 15 highly-responsive chemical components in Shuxin Anshen Decoction,which was in line with the core components predicted by network pharmacology.Animal experiments demonstrated that compared with the model control group,the mice trea-ted with Shuxin Anshen Decoction(20.5 g/kg)had increased body weights and sucrose preferences,as well as reduced forced swimming time and latency in novelty-suppressed feeding test(P＜0.05).Nissl staining showed that mice treated with Shuxin Anshen Decoction(20.5 g/kg)had more regularly arranged neurons in the hippocampal CA3 region,reduced pericellular space,and abundant Nissl bodies,in contrast to the model control group.Western blot indicated that Shuxin Anshen Decoction(20.5 g/kg)upregulated the protein expressions of TrkB,p-Akt,BDNF,and CREB in the hippocampus(P＜0.05).Conclusion:Shuxin Anshen Decoction exerted its therapeutic effects on de-pression by acting on targets such as ESR1 and AKT1 and intervening in the BDNF/TrkB signaling pathway and downstream proteins possibly through its main components such as quercetin,β-sitosterol,paeoniflorin,spinosin,and gingerol,etc.Its mechanism might involve upregulating TrkB,p-Akt,BDNF,and CREB proteins and improving the plasticity of hippocampal neurons.
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