Investigation into the antidepressant mechanism of the Guizhi-Baishao herbal pair based on network pharmacology and molecular docking.

This study aims to explore the antidepressant mechanism of the Guizhi-Baishao herbal pair using network pharmacology and molecular docking methods, providing a basis for fundamental research and clinical application. Active compounds and target proteins of Guizhi and Baishao were retrieved from the TCMSP database using oral bioavailability ≥ 30% and drug-likeness ≥ 0.18 as screening criteria. Depression-related therapeutic targets were identified through databases such as GeneCards, OMIM, TTD, and DrugBank, and the intersection of drug targets and disease targets was obtained. A protein-protein interaction network was constructed using the STRING database, and topological analysis was performed with Cytoscape 3.10.3 software. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the intersecting targets were conducted via the DAVID database. Molecular docking analyses were performed using AutoDockTools 1.5.7 and PyMOL 3.1.3, with further validation of key compounds through AutoDock Vina. A total of 20 potential active compounds and 87 corresponding targets of the Guizhi-Baishao pair were identified, along with 5502 depression-related targets, yielding 77 intersecting targets. Protein interaction analysis revealed core targets potentially influenced by the active compounds, including RAC-α serine/threonine protein kinase, prostaglandin G/H synthase, interleukin (IL)-6, tumor necrosis factor (TNF), estrogen receptor 1, acetylcholinesterase, sodium-dependent neurotransmitter transporter, peroxisome proliferator-activated receptor γ, cytochrome P450 3A4 enzyme, and NF-κB p65 protein. With P < .05 as the threshold, 415 Gene Ontology functional terms and 127 Kyoto Encyclopedia of Genes and Genomes pathways were enriched for the Guizhi-Baishao pair's antidepressant effects. Molecular docking of core targets with corresponding active compounds indicated affinities of <-5 kJ/mol between the active compounds and target proteins. The antidepressant mechanism of the Guizhi-Baishao pair may involve multiple active compounds (such as kaempferol, dihydroquercetin, β-sitosterol, epicatechin, catechin, and paeoniflorin) regulating core proteins like RAC-αserine/threonine protein kinase, prostaglandin G/H synthase, IL-6, TNF, estrogen receptor 1, acetylcholinesterase, peroxisome proliferator-activated receptor γ, cytochrome P450 3A4 enzyme, and NF-κB p65 protein, as well as pathways related to apoptosis, T helper 17 cell differentiation, TNF, IL-17, and NF-κB signaling. This regulation may inhibit apoptosis of cells and hippocampal neurons, neurotransmitter disturbances, oxidative stress, and inflammatory responses.