UPLC-MS/MS and network pharmacology-based antidepressant study of Chaihu Jia Longgu Muli decoction

Background Depression is a mental disorder characterized by persistent low mood and cognitive impairment. Chaihu Jia Longgu Muli Decoction (CLMD) is an effective and relatively safe therapeutic method for depression. However, the chemical composition of CLM and its underlying mechanisms remain unclear. Objective This study aimed to explore the potential mechanisms of CLMD in treating depression by integrating UPLC-MS/MS and network pharmacology. Methods Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the ingredients of CLMD. The targets of these components were predicted and screened using the TCMSP, SuperPred, and SwissTargetPrediction databases. The disease targets related to depression were obtained from the GeneCards, OMIM, and DisGeNET databases. The protein-protein interaction (PPI) networks of CLMD and depression were constructed using the STRING database, and Origin 2022 software was used to identify cross-targets by screening the core-acting targets. A network diagram was constructed using Cytoscape3.7.2 software. The DAVID database was used for GO and KEGG enrichment analysis of the core genes. Then, molecular docking was performed to verify the results using AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL2.3.0, and Ligplot V 2.2.4 software. Molecular dynamics simulation was performed by iNODS. Finally, a series of in vitro experiments were performed to examine the function of baicalin in corticosterone-stimulated HT22 cells. Results A total of 1011 components in CLMD were detected, and 778 targets were identified through database screening. Key active ingredients included baicalin, luteolin, rhein, etc . A total of 472 targets were screened based on the degree values, among which there were 3 core target genes: PIK3R1, AKT1, and MAPK1. There were many enriched significant pathways, including PI3K/AKT and MAPK pathways. Baicalin binds well to the three core proteins PIK3R1, AKT1, and MAPK1. Baicalin inhibited corticosterone-induced depression-like neuronal injury through activating PI3K/AKT and MAPK/ERK pathways. Conclusion These results suggested that the antidepressant effects of CLMD could be achieved by its active ingredient baicalin, which targeted PIK3R1, AKT1, and MAPK1 to affect PI3K/AKT and MAPK/ERK pathways. This study provided a basis for further in-depth study on the therapeutic mechanism of CLMD in depression.