Objective To explore the pharmacodynamic substances and mechanism of Chaihu Shugan Powder(CHSGP)in the treatment of depression and to verify the experimental results.Methods The chemical constituents of CHSGP were analyzed by UPLC-Q-TOF-MS/MS.Traditional Chinese Medicine System Pharmacology Database(TCMSP)and SwisTargetPrediction database were used to obtain and screen the component target.Differential gene analysis and weighted gene co-expression network analysis(WGCNA)analysis were performed on GSE19738 gene chip data using Limma package and hclust function,and depression related targets were obtained and intersected with component targets.The chemical composition-target network diagram was drawn,the degree value was calculated,and the pharmacodynamic substances were screened.The intersection genes were concentrated by GO and KEGG,followed by LASSO regression analysis and SVM analysis,to obtain the potential targets of CHSGP in the treatment of depression,and ROC survival analysis and molecular docking verification as well as experimental verification based on zebrafish depression model.Results A total of 126 chemical constituents were identified from CHSGP water extracts,114 intersections of"chemical-depression"were identified,and 44 potential pharmacodynamic substances with a degree ≥11(median)were identified.The top 5 components were saikosaponin A,nobiletin,2',4,4'-trihydroxy-chalcone,ligustrolide A and naringin chalcone.Five key genes,FOS,TNF,NF-κB1,CXCR2 and IDO1,were obtained as potential targets for GHSGP anti-depression.Molecular docking results showed that the five key components had good binding energy with five potential targets,and the binding energy with NF-κB1 and TNF was the best.In vivo studies,under the premise of determining the efficacy of CHSGP as an antidepressant,CHSGP can significantly reduce the expression levels of pro-inflammatory factors IL-6 and TNF-a in zebrafish depression models(P＜0.001).At the gene level,CHSGP could significantly reduce the mRNA expression levels of NF-κB1,TNF-a and IL-6 in zebrafish depression model(P＜0.05).Conclusion CHSGP can regulate the TNF-α/NF-κB signaling pathway through a variety of components such as saikosaponin A and chenorin to play an antidepressant role.
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