OBJECTIVE: To explore the mechanism of Huanglian Ejiao decoction in the treatment of depression. METHODS: Effective components and targets of Huanglian Ejiao decoction were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other database. Component-disease-target network was established by Cytoscape. Protein-protein interaction（PPI） of intersection targets was established based on STRING platform. Gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed based on DAVID platform. AutoDock software was used for the molecular docking. In vitro experiments

the PC12 cell model was administered with quercetin and baicalein

cell activity and expression of related target proteins were detected. RESULTS: A total of 73 antidepressant active ingredients were screened from Huanglian Ejiao decoction

including 577 targets

of which 283 targets were related to depression. Active ingredients such as quercetin

baicalein and beta-sitosterol may play an important role. PPI results showed that signal transducer and activator of transcription 3

vascular endothelial growth factor A

interleukin（IL） 1β

IL-6

tumor necrosis factor（TNF） and protein kinase B1 were the core targets of Huanglian Ejiao decoction in the treatment of depression. Molecular docking results showed that there was a good binding ability. GO and KEGG enrichment analysis showed that 283 targets were involved in hypoxia response

postsynaptic membrane and plasma membrane

as well as signal pathways such as hypoxia inducible factor（HIF） 1

TNF and cyclic adenosine monophosphate（cAMP）. Results of in vitro experiments showed that quercetin and baicalein could effectively improve the apoptosis rate of PC12 cells and reduce the expression of inflammatory factors. CONCLUSIONS: After the prediction of network pharmacology and verification of in vitro experiments

Huanglian Ejiao decoction can treat depression by regulating inflammatory factors

cytokines and oxidative stress through HIF-1

TNF

cAMP and other signaling pathways.