基于网络药理学和分子对接技术研究柴胡桂枝汤治疗抑郁症的作用机制  

Study on the mechanism of Chaihu Guizhi Decoction in the treatment of depression based on network pharmacology and molecular docking technology

作　　者：蓝绍航 罗俊[1,2] 李娜娜 罗业浩 陈秋霞 陈静芹 李宏一 方刚 LAN Shaohang;LUO Jun;LI Nana;LUO Yehao;CHEN Qiuxia;CHEN Jingqin;LI Hongyi;FANG Gang(Key Laboratory of Applied Basic Research of Guangxi Zhuang Medicine,Guangxi University of Chinese Medicine,Guangxi Zhuang Autonomous Region,Nanning,530001,China;Modern Educational Technology and Information Center,Guangxi University of Chinese Medicine,Guangxi Zhuang Autonomous Region,Nanning,530200,China;Guoyitang,Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Guangxi Zhuang Autonomous Region,Nanning,530011,China)

机构地区：[1]广西中医药大学广西壮医应用基础研究重点实验室,广西南宁530001 [2]广西中医药大学现代教育技术与信息中心,广西南宁530200 [3]广西中医药大学附属瑞康医院国医堂,广西南宁530011

出　　处：《中国医药导报》2021年第31期22-27,F0004,共7页China Medical Herald

基　　金：广西壮族自治区卫生健康委重点(重点培育)实验室项目(桂卫科教发〔2020〕17号);广西医学高层次学科带头人培养项目(桂卫科教发〔2020〕15号)。

摘　　要：目的运用网络药理学和分子对接技术研究柴胡桂枝汤治疗抑郁症的作用机制。方法利用中药系统药理学数据库和分析平台收集柴胡桂枝汤中9味中药的主要化学成分和作用靶点。通过GeneCards、药物基因组学知识库、在线人类孟德尔遗传、DrugBank、TTD等数据库获取抑郁症相关靶点,利用STRING在线平台构建潜在靶点蛋白质-蛋白质相互作用网络并利用R语言获取GO功能富集及KEGG通路分析。运用Cytoscape3.7.2构建“活性成分-疾病靶点”网络并对其进行拓扑分析。最后利用AutoDock vina等软件对网络中度值较高的活性成分与核心靶点进行分子对接验证。结果筛选到柴胡桂枝汤中槲皮素、山柰酚等154种主要化学成分和250个相关靶点,其中关键靶点有JUN、Akt1、ESR1等;GO功能富集分析共得到2900条富集结果,主要涉及对脂多糖的反应、氧化应激反应等生物过程的调节;KEGG通路分析共得到170条通路富集结果,主要涉及MAPK信号通路、PI3K-Akt信号通路等;分子对接结果显示主要活性成分与核心靶点结合力强。结论本研究初步表明了柴胡桂枝汤通过多成分、多靶点、多通路发挥治疗抑郁症的协同作用机制。Objective To study the mechanism of Chaihu Guizhi Decoction in the treatment of depression by network pharmacology and molecular docking technology.Methods Traditional Chinese medicine systems pharmacology database and analysis platform was used to collect the main chemical components and targets of nine traditional Chinese medicines in Chaihu Guizhi Decoction.Depression related targets were obtained from GeneCards,pharmacogenomics knowledgebase,online Mendelian inheritance in man,DrugBank,TTD,and other databases.Proteinprotein interaction network of potential targets was constructed by using STRING online platform,and GO functional enrichment analysis and KEGG pathway analysis were obtained by R language.The“active component-disease target”network was constructed and topologically analyzed by Cytoscape3.7.2.Finally,AutoDock vina and other software were used to verify the molecular docking between the active ingredients with high network intermediate value and the core target.Results A total of 154 chemical constituents including quercetin and kaempferol were screened and 250 related targets were identified,among which the key targets were JUN,Akt1,and ESR1.A total of 2900 enrichment results were obtained by GO functional enrichment analysis,which mainly involved the regulation of biological processes such as lipopolysaccharide response and oxidative stress response.A total of 170 pathways were enriched by KEGG pathway analysis,mainly involving MAPK signaling pathway,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the main active ingredients had strong binding ability with the core target.Conclusion This study preliminarily shows that Chaihu Guizhi Decoction plays a synergistic role in the treatment of depression through multiple components,multiple targets and multiple pathways.

关 键 词：柴胡桂枝汤 抑郁症 网络药理学 分子对接 

分 类 号：R749.4[医药卫生—神经病学与精神病学]