OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the...OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.展开更多
基金the National Natural Science Foundation of China:Study on the Biological Basis of Jiawei Danzhi Xiaoyaosan in Treatment of Depression based on Network Pharmacology and Proteomics(No.81973739)Natural Science Excellent Youth Fund of Henan Province:the Mechanism of Baicalin Regulates the GSK3B-Mediated Axoplasmic Transport in the Treatment of Depression(No.202300410249)+1 种基金Science and Technology Research Project of Henan Province:Study on the Antidepressant Mechanism of Jiawei Danzhi Xiaoyaosan based on the NOD-like Receptor Thermal Protein Domainassociated Protein and Tripartite Motif-containing Protein 31 Ubiquitination Pathway(No.222102310233)Study on the Mechanism of Jiawei Danzhi Xiaoyaosan in the Treatment of Depression by Regulating M1/M2 Polarization and Microglia Autophagy(No.232102310419)。
文摘OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.
