| Abstract |
Objective Employing network pharmacology, GEO analysis,and molecular docking methods to explore the active constituents and underlying mechanisms of bupleurum- cyperus rotundus medicine in treating depression, thus laying a partial theoretical groundwork and offering directional guidance for future research on its mechanism.. Methods Active components and associated targets of Bupleurum and Cyperus rotundus were identified and screened using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and String databases; The Human Gene Database（GeneCards） and Online Mendelian Inheritance in Man（OMIM） databases were employed to pinpoint depression-related targets. Once we identified the common targets of the disease and drug, the String platform and Cytoscape 3.9.1 software were employed to construct a network symbolizing these overlapping targets and active elements. This network was then evaluated using Protein-Protein Interactions（PPI） network analysis. Through bioinformatics analysis of selected datasets from m the Gene Expression Database（GEO）, genes exhibiting differences in human depression were identified. Intersection of these genes with core targets associated with key pathways was performed to validate the targets reliability in clinical specimens. This led to the identification of primary targets for treating depression clinically. Molecular docking studies were then executed using Pymol software to affirm the drugs efficacy on the identified targets. Results In the Bupleurum-Cyperus medication, 25 active constituents were identified, four of which were common components, which interact with 123 depression-related targets. GEO analysis yielded 1,217 differential genes for depression, and after intersecting with 67 core genes corresponding to key pathways, five core targets were identified for the treatment of human depression using Bupleurum-Cyperus medicine, namely Mitogen activated protein kinase 14（MAPK14）, Matrix metalloproteinase 9（MMP9）, Epidermal Growth Factor（EGF）, MYC proto-oncogene（MYC）, and Monoamine oxidase A（MAOA）. Molecular docking indicated that the key targets form stable structures with most of the core components. Conclusion bupleurum- cyperus rotundus may exert its therapeutic impact on depression through the key targets of MAPK14, MMP9, EGF, MYC, and MAOA.
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