AIM:This study investigates the antidepressant mechanism of Jieyu-Anshen formula combined with selenium in chronic unpredictable mild stress(CUMS)mice through network pharmacology and animal experiments.METHODS:Potential drug targets were identified using the TCMSP,Genecards,and STRING databases.A protein-pro-tein interaction network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)enrichment analyses and molecular docking validation.Sixty male KM mice were divided into six groups:control,model,selenium,Jieyu Anshen formula,selenium+Jieyu Anshen formula,and fluoxetine.Depression-like behav-iors were assessed using the tail suspension test,forced swimming test,and elevated plus-maze test.Enzyme-linked immu-nosorbent assay(ELISA)was used to measure hippocampal levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,5-hydroxytryptamine(5-HT),and dopamine(DA).Histopathological changes in the hippocampus were ex-amined using hematoxylin and eosin(HE)staining.Additionally,protein expression levels of nuclear factor-κB p65(NF-κB p65),phospho-NF-κB-p65(p-NF-κB p65),prostaglandin-endoperoxide synthase 2(PTGS2),glutathione peroxidase 4(GPX4),and selenoprotein S(SelS)were detected through immunohistochemistry and Western blot.RESULTS:Jieyu-Anshen formula combined with selenium significantly improved depression-like behaviors in CUMS mice,reduced inflammatory cytokine(IL-6,TNF-α and IL-1β)levels,restored the levels of 5-HT and DA,and inhibited NF-κB signal-ing pathway activation.CONCLUSION:Jieyu Anshen formula combined with selenium significantly improved depres-sion-like behaviors in CUMS mice,potentially by improving hippocampal morphology,modulating the NF-κB signaling pathway,suppressing inflammatory factor expression,and enhancing hippocampal 5-TH and DA levels.

AIM:This study investigates the antidepressant mechanism of Jieyu-Anshen formula combined with selenium in chronic unpredictable mild stress(CUMS)mice through network pharmacology and animal experiments.METHODS:Potential drug targets were identified using the TCMSP,Genecards,and STRING databases.A protein-pro-tein interaction network was then constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)enrichment analyses and molecular docking validation.Sixty male KM mice were divided into six groups:control,model,selenium,Jieyu Anshen formula,selenium+Jieyu Anshen formula,and fluoxetine.Depression-like behav-iors were assessed using the tail suspension test,forced swimming test,and elevated plus-maze test.Enzyme-linked immu-nosorbent assay(ELISA)was used to measure hippocampal levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,5-hydroxytryptamine(5-HT),and dopamine(DA).Histopathological changes in the hippocampus were ex-amined using hematoxylin and eosin(HE)staining.Additionally,protein expression levels of nuclear factor-κB p65(NF-κB p65),phospho-NF-κB-p65(p-NF-κB p65),prostaglandin-endoperoxide synthase 2(PTGS2),glutathione peroxidase 4(GPX4),and selenoprotein S(SelS)were detected through immunohistochemistry and Western blot.RESULTS:Jieyu-Anshen formula combined with selenium significantly improved depression-like behaviors in CUMS mice,reduced inflammatory cytokine(IL-6,TNF-α and IL-1β)levels,restored the levels of 5-HT and DA,and inhibited NF-κB signal-ing pathway activation.CONCLUSION:Jieyu Anshen formula combined with selenium significantly improved depres-sion-like behaviors in CUMS mice,potentially by improving hippocampal morphology,modulating the NF-κB signaling pathway,suppressing inflammatory factor expression,and enhancing hippocampal 5-TH and DA levels.