OBJECTIVE To study the therapeutic effect of saikosaponins and paeoniflorin on rats with premenstrual dysphoric disorder(PMDD) model of liver Qi depression and the effect on neurotransmitters in hippocampal brain area. METHODS The PMDD rat model of liver Qi depression was prepared by the time-chosen chronic restraint stress method, and the depressive symptoms of rats were evaluated by the intervention of saikosaponins and paeoniflorin, the open field experiment and forced swimming experiment, and the changes of neurotransmitter levels in the hippocampal brain region of rats were detected by UHPLC-MS/MS target metabolomics. RESULTS The levels of 5-HT, Glu, GABA and NE in the hippocampal brain area of PMDD rats were significantly increased, and the levels of 5-HT, Glu, GABA, NE, DA and E were not statistically significant from those of the normal group after the intervention of saikosaponins and paeoniflorin. CONCLUSION Saikosaponins and paeoniflorin alleviates depression in rats with PMDD by regulating neurotransmitter levels, and it may be the pathway for the clinical treatment of PMDD with liver qi depression in the formulations of Bupleuri Radix and Paeoniae Radix Alba.

OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression.