中国药房2025,Vol.36Issue(12):1449-1456,8.DOI:10.6039/j.issn.1001-0408.2025.12.06
芦丁改善经前烦躁障碍肝气郁证抑郁症状的机制研究
Study on the mechanism of rutin in ameliorating depressive symptoms associated with premenstrual dysphoric disorder characterized by liver qi stagnation syndrome
摘要
Abstract
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.关键词
芦丁/经前烦躁障碍/肝气郁证/脑源性神经营养因子/神经元损伤Key words
rutin/premenstrual dysphoric disorder/liver qi stagnation syndrome/brain-derived neurotrophic factor/neuronal damage分类
医药卫生引用本文复制引用
张艺伟,宋现良,任亚爽,郭德第,宋润蔚,陈玺泰,赵怀伟,宋春红..芦丁改善经前烦躁障碍肝气郁证抑郁症状的机制研究[J].中国药房,2025,36(12):1449-1456,8.基金项目
国家重大新药创制课题(No.2017ZX09301064) (No.2017ZX09301064)
山东省自然科学基金面上项目(No.ZR2020MH341) (No.ZR2020MH341)
山东省中医药科技项目(No.2021M121) (No.2021M121)