Mechanisms of Baishao () and Gancao () on major depressive disorder: network pharmacology and o validation

To elucidate the potential molecular mechanisms of Baishao (Radix Paeoniae Alba) (APR) and Gancao (Radix Glycyrrhizae) (GR) in the treatment of major depressive disorder (MDD).

Based on the network pharmacology strategy, the therapeutic targets of APR-GR for MDD are predicted, differentially expressed genes from the Integrated Gene Expression database for MDD patients. Topological networks are constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched, their pharmacological potential molecular mechanisms are discussed, and molecular docking analysis is performed to further motivate compositional and target interactions. Finally, the CUMS mouse model is used for validation.

Based on the pharmacological network analysis, 17 candidate genes were identified, including muscarinic acetylcholine receptor M1(CHRM1), muscarinic acetylcholine receptor M2 (CHRM2), β2-adrenergic receptor (ADRB2), adrenergic α1A receptor (ADRA1A) and 5-hydroxytryptamine transfer protein (SLC6A4), etc. which are primarily involved in reactive oxygen species metabolism, neural response, oxidative stress response and other biological processes. Further analysis revealed that these targets are closely related to Ca²⁺, cyclic adenosine monophosphate, etc., and exhibit optimal binding sites after molecular docking. Finally, in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models, increasing brain levels of 5-hydroxytryptamine, dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone, corticosterone and adreno cortico tropic hormone, while upregulating the expression of CHRM1, CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2.

This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.