基于代谢组学与网络药理学的百合地黄汤抗抑郁作用机制研究  

Antidepressant mechanism of Baihe Dihuang Decoction based on metabolomics and network pharmacology

作　　者：胡超 杨蕙[1] 赵洪庆[2] 黄思琪 刘红宇[1] 张水寒[3] 唐林[1] HU Chao;YANG Hui;ZHAO Hong-qing;HUANG Si-qi;LIU Hong-yu;ZHANG Shui-han;TANG Lin(the First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Academy of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学,湖南长沙410208 [3]湖南省中医药研究院,湖南长沙410208

出　　处：《中国中药杂志》2025年第1期10-18,共9页China Journal of Chinese Materia Medica

基　　金：湖南省自然科学基金科药联合项目(2022JJ80093,2024JJ8151);湖南省自然科学基金优秀青年项目(2024JJ4033);湖南省教育厅科学研究项目(22B0362);湖南省卫生健康委科研计划项目(202213055417);湖南省中医药科研计划项目(B2023054);湖南中医药大学中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(2022FTKFJJ11);国家自然科学基金面上项目(82174069)。

摘　　要：百合地黄汤是治疗抑郁症的经典名方,该研究采用代谢组学整合网络药理学探究其治疗抑郁症的作用机制。50只雄性SD大鼠随机分为正常对照组、模型组、阳性药组、百合地黄汤高剂量组、百合地黄汤低剂量组。采用慢性不可预见性温和应激(CUMS)的方法建立抑郁大鼠模型;通过旷场实验和强迫游泳实验检测行为学变化;利用代谢组学技术对血清及海马组织代谢谱进行分析,筛选差异代谢物及相关代谢通路;结合网络药理学及分子对接初步阐明百合地黄汤改善抑郁症代谢异常的关键靶点及核心有效成分,并构建“成分-靶点-代谢物-通路”调控网络。百合地黄汤可显著改善CUMS大鼠抑郁样行为,显著调节血清中12个差异代谢物与海马中27个差异代谢物,主要涉及色氨酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,丙氨酸、天冬氨酸和谷氨酸代谢,酪氨酸代谢,嘌呤代谢等。毛蕊花糖苷、异毛蕊花糖苷、王百合苷B等为改善抑郁症代谢异常的关键有效成分,表皮生长因子受体(EGFR)、原癌基因酪氨酸蛋白激酶(SRC)、糖原合成酶激酶3β(GSK3β)、雄激素受体(AR)等为改善抑郁症代谢异常的关键核心靶点。该研究基于网络调控视角初步揭示了百合地黄汤改善抑郁症代谢异常的作用机制,为百合地黄汤的临床应用及后续研究提供了借鉴。The Baihe Dihuang Decoction(BDD)is a representative traditional Chinese medicine formula that has been used to treat depression.This study employed metabolomics and network pharmacology to investigate the mechanism of BDD in the treatment of depression.Fifty male Sprague-Dawley(SD)rats were randomly assigned to the normal control group,model group,fluoxetine group,and high-and low-dose BDD groups.A rat model of depression was established through chronic unpredictable mild stress(CUMS),and the behavioral changes were detected by forced swimming test and open field test.Metabolomics technology was used to analyze the metabolic profiles of serum and hippocampal tissue to screen differential metabolites and related metabolic pathways.Additionally,network pharmacology and molecular docking techniques were used to investigate the key targets and core active ingredients of BDD in improving metabolic abnormalities of depression.A"component-target-metabolite-pathway"regulatory network was constructed.BDD could significantly improve depressive-like behavior in CUMS rats and regulate 12 differential metabolites in serum and 27 differential metabolites in the hippocampus,involving tryptophan metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis,alanine,aspartate,and glutamate metabolism,tyrosine metabolism,and purine metabolism.Verbascoside,isorbascoside,and regaloside B were the key active ingredients for improving metabolic abnormalities in depression.Epidermal growth factor receptor(EGFR),protooncogene tyrosine-protein kinase(SRC),glycogen synthase kinase 3β(GSK3β),and androgen receptor(AR)were the key core targets for improving metabolic abnormalities of depression.This study offered a preliminary insight into the mechanism of BDD in alleviating metabolic abnormalities of depression through network regulation,providing valuable guidance for its clinical use and subsequent research.

关 键 词：百合地黄汤 抑郁症 代谢组学 网络药理学 机制 

分 类 号：R285.5[医药卫生—中药学]