基于整合药理学平台的柴胡-黄芩药对抗抑郁的分子机制研究

Molecular mechanism of Bupleuri Radix and Scutellariae Radix drug pair for depression based on integrative pharmacology platform of traditional Chinese medicine

小柴胡汤为中医经典方药,现代研究证明其对抑郁症的疗效确切。但由于中药复方的复杂性,其抗抑郁症的药理学机制难以明晰。柴胡-黄芩是小柴胡汤核心配伍,该研究以柴胡-黄芩为研究对象,借助整合药理学平台,对其治疗抑郁症的分子机制进行研究探讨。对柴胡-黄芩药对预测共得到116个活性成分,其中柴胡62个,主要为柴胡皂苷类、酸类、醇类等;黄芩54个,主要为黄酮类和苷类。其抗抑郁作用涉及118个核心靶标,其中包括22个直接靶标,如五羟色胺受体（HTR2C）,转录激活因子1,2（ATF1,ATF2）,δ型阿片受体（OPRD1）,μ型阿片受体（OPRM1）,κ型阿片受体（OPRK1）,肌醇单磷酸酶1（IMPA1）,Toll样受体4（TLR4）,组胺H1受体（HRH1）,神经营养因子酪氨酸激酶受体1（NTRK1）,糖原合成酶激酶-3β（GSK3β）等;其抗抑郁作用涉及RNA聚合酶Ⅱ启动子转录的正调控、转录因子的结合、细胞质、转录调控DNA模板、酶结合、内分泌系统、神经系统、神经营养因子信号通路、细胞生长和死亡、信号转导分子、甲状腺激素信号传导通路等相关生物过程和代谢通路。该研究为进一步研究该药对抗抑郁作用机制提供科学依据。

Xiaochaihu decoction is a classic prescription of traditional Chinese medicine. Modern research has proved its anti-depression effect. However,its pharmacological mechanism for anti-depression effect is difficult to be unveiled because of the complexity of compound Chinese medicines. Bupleuri Radix and Scutellariae Radix is the core drug pair of Xiaochaihu decoction. In this research,Bupleuri Radix and Scutellariae Radix were analyzed by the integrative pharmacology platform to study its molecular mechanism for antidepression. One hundred and sixteen active ingredients were predicted,62 for Bupleuri Radix,mainly including saikosaponins,acids,alcohols,and 54 for Scutellariae Radix,mainly including flavonoids and glycosides. Its anti-depression effect was relevant to 118 core targets,including 22 known disease targets,such as serotonin receptor（ HTR2 C）,activating transcription factor（ ATF1,ATF2）,δ opioid receptor（ OPRD1）,μ opioid receptor（ OPRM1）,κ opioid receptor（ OPRK1）,inositol monophosphatase（ IMPA1）,Toll-like receptor 4（ TLR4）,histamine H1 receptor（ HRH1）,neurotrophic factor tyrosine kinase receptor1（ NTRK1）,Glycogen synthetase kinase 3β（ GSK3β）,etc. The antidepressant effect involved positive regulation of transcription from RNA polymeraseⅡpromoter,transcription factor binding,cytosol,transcriptional regulation of DNA template,enzyme binding,endocrine system,nervous system,neurotrophin signaling pathway,cell growth and death,signal transduction,thyroid hormone signaling pathway and other related biological processes and metabolic pathways. This study provides a scientific evidence for further study of the anti-depression mechanism of this drug pair.