基于网络药理学和分子对接探讨“寒凉”中药黄连、黄芩、黄柏治疗痴呆的作用机制  

Mechanism of“cold and cool”traditional Chinese medicines Coptis chinensis Franch,Scutellaria baicalensis Georgi,and Phellodendron chinense Schneid in treatment of dementia based on network pharmacology and molecular docking

作　　者：高书春 唐瑞欣 赵洋 邓雪阳 浮姣 GAO Shuchun;TANG Ruixin;ZHAO Yang;DENG Xueyang;FU Jiao(Department of Endocrinology and Metabolism,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;China Pharmaceutical University College of Traditional Chinese Medicine)

机构地区：[1]西安交通大学第一附属医院内分泌代谢科,西安710061 [2]中国药科大学中药学院

出　　处：《山西医科大学学报》2023年第5期652-662,共11页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(82074045)。

摘　　要：目的 基于网络药理学和分子对接探讨“寒凉”中药黄连、黄芩、黄柏(三黄)治疗痴呆的作用机制。方法 通过数据挖掘《宣明论方》,筛选出符合“寒凉”属性并且是治疗“痴呆症”的常见中药黄芩、黄连、黄柏。通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)数据库检索“三黄”的有效成分和作用靶点,在GeneCards、DrugBank等数据库检索痴呆症(dementia)靶点。利用Cytoscape3.7.2构建“药物-成分-靶点”网络,用VENNY2.1获得“三黄”和痴呆症的交集靶点后,构建蛋白质互作网络(protein-protein interaction networks, PPI),利用Metascape库对核心靶点进行GO、KEGG富集分析,并构建“三黄”药物-成分-靶点-通路-疾病网络,最后利用分子对接,以反向验证“三黄”活性成分与核心靶点之间的关系。结果 筛选出“三黄”治疗痴呆症的重要活性成分有槲皮素、β-谷甾醇、小檗碱、黄连碱等,关键核心靶点有TP53、AKT1、IL6、JUN、MAPK14、TNF等。KEGG通路分析有129条,主要有AGE-RAGE信号介导的糖尿病并发症通路、PI3K-Akt信号通路、钙信号通路等;GO功能中,分子功能117条,细胞组成61条,生物过程1 366条,主要涉及配体激活转录因子活性、DNA结合转录因子结合等分子功能,膜微区、突触后膜等细胞组成,活性氧代谢过程、对脂多糖的反应、炎症反应等生物过程。分子对接结果可以看出重要活性成分与核心靶点全部对接成功。结论 本研究结果表明,“三黄”特有的药性优势,可以通过多成分、多靶点、多通路的方式治疗痴呆症,为“三黄”治疗痴呆症临床应用和机制研究提供了依据。Objective To explore the mechanism of“cold and cool”traditional Chinese Medicines Coptis chinensis Franch,Scutellaria baicalensis Georgi,and Phellodendron chinense Schneid in the treatment of dementia based on network pharmacology and molecular docking.Methods Through data mining of Xuanming Lun Fang,the common traditional Chinese medicines Coptis chinensis Franch,Scutellaria baicalensis Georgi,and Phellodendron chinense Schneid(also called“Sanhuang”)in treatment of dementia were selected.The active ingredients and targets of“Sanhuang”were retrieved through the TCMSP database,and the targets of dementia were searched in GeneCards and DrugBank.The network of“drugs-components-targets”was constructed by Cytoscape3.7.2.The intersection targets of“Sanhuang”and dementia were obtained by VENNY2.1,and the PPI network was constructed.The core targets were analyzed with Metascape library for GO and KEGG,and a“Sanhuang”drug-component-target-pathway-disease network was built.Finally,the molecular docking was used to verify the relationship between the active ingredients of“Sanhuang”and the core target.Results The active ingredients of“Sanhuang”for dementia were quercetin,beta-sitosterol,berberine,coptisine,etc.The key core targets included TP53,AKT1,IL6,JUN,MAPK14,TNF,etc.A total of 129 KEGG pathways were identified,including AGE-RAGE signaling pathway in diabetic complications,PI3K-Akt signaling pathway,calcium signaling pathway and etc.GO analysis showed that molecular functions were enriched in 117 items(mainly ligand activation of transcription factor activity and DNA binding transcription factor binding),the cellular locations were enriched in 61 items(membrane microdomain and postsynaptic membrane),and the biological process was enriched in 1366 items(reactive oxygen species metabolic process,response to lipopolysaccharide,and inflammatory response).Finally,all the active ingredients were successfully docked with the core targets.Conclusion“Sanhuang”has unique pharmaceutical advantag

关 键 词：痴呆症 网络药理学 分子对接 黄芩 黄连 黄柏 数据挖掘 

分 类 号：R742[医药卫生—神经病学与精神病学]