Background. Major Depression Disorder (MDD) is a common mental disease that has become one of the world’s major medical diseases. Currently, the Fructus Aurantii (FA) has been widely used to treat depression. However, the active substance ingredients and potential mechanisms of the shell antidepression have not yet been clarified. Method. First, we used ultraperformance liquid chromatography-quadrupole/time-of-flight tandem mass (UPLC-QTOF-MS/MS) technology to identify the chemical composition of the FA. Then, it is predicted for active ingredients, pharmaceutical disease target screening by DiscoveryStudio 2016 (DS), Metascape, and other databases, PPI network diagram, and FC core pathway. Finally, the system network pharmacology results are verified by molecular contact verification. Results. Forty-six compounds in FA were identified, and twelve active ingredients were determined. Various database information, PPI network analysis of 41 intersections, and 20 core targets including DRD2, MTOR, FASP3, and PIK3P1 were integrated. Finally, the MDD treatment is indicated by molecular docking, and the most relevant potential signal pathway is the PI3K-Akt signaling pathway.

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