Integrating Network Pharmacology, Molecular Docking and Pharmacological Evaluation for Exploring the Polyrhachis vicina Rogers in Ameliorating Depression

Purpose: To investigate the mechanisms of antidepressant action of active fraction of Polyrhachis vicina Rogers (AFPR) through network pharmacology, molecular docking and experimental validation. Methods: GC-MS was used to predict chemical compounds, corresponding databases were used to predict chemical compound targets and depression targets, Cytoscape software was used to construct and analyze the protein interaction network map, DAVID database was used to analyze gene ontology (GO) and KEGG signaling pathway, and AGFR software was used to perform molecular docking. Subsequently, the underlying action mechanisms of AFPR on depression predicted by network pharmacology analyses were experimentally validated in a CORT-induced depression model in vitro and in vivo. Results: A total of 52 potential targets of AFPR on antidepressant were obtained. GO is mainly related to chemical synaptic transmission, signal transduction and others. KEGG signaling pathways are mainly related to cAMP signaling pathway and C-type lectin receptor signaling pathway. The experiment results showed that AFPR significantly increased the expression of PRKACA, CREB and BDNF in mouse brain tissue and PC12 cells. Furthermore, after interfered of cAMP in PC12 cells, the decreased expression of PRKACA, CREB and BDNF was reversed by AFPR. Conclusion: AFPR may exert antidepressant effects through multiple components, targets and pathways. Furthermore, it could improve neuroplasticity via the cAMP signaling pathway to improve depression-like symptoms. Graphical Abstract: Keywords: PC12 cells, BDNF, corticosterone, CAMP signaling pathway, GC-MS