基于网络药理学和分子对接研究枳实薤白桂枝汤治疗心血管疾病的作用机制  

Action Mechanism of Zhishixiebaiguizhi Decoction in the Treatment of Cardiovascular Disease Based on Network Pharmacology and Molecular Docking

作　　者：闫浩 刘潇潇 孙轲强 左振宇[1] 刘靖丽[1] 宋逍[1] Yan Hao;Liu Xiaoxiao;Sun Keqiang;Zuo Zhenyu;Liu Jingli;Song Xiao(College of Pharmacy,Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712046,China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046

出　　处：《中国药师》2021年第3期405-415,420,共12页China Pharmacist

基　　金：科技部国家重点研发计划中医药现代化研究重点专项(编号:2019YFC1711200);陕西省自然科学基础研究计划(编号:2019JQ-874);陕西省教育厅专项科研计划(编号:19JK0232)。

摘　　要：目的:探究复方枳实薤白桂枝汤治疗心血管疾病的作用机制。方法:基于中药系统药理学数据库与分析平台(TCMSP)数据库筛选枳实薤白桂枝汤的有效成分及靶点基因;通过基因卡片(Gene Cards)和在线人类孟德尔遗传(OMIM)数据库筛选疾病的靶点基因,将药物有效成分靶标与疾病靶标映射;采用Cytoscape 3.7.1构建药物-成分-靶点-疾病关系图,寻找关键作用成分。运用STRING数据库,得到蛋白互作核心基因。将关键作用成分与核心基因中的前3个做分子对接。利用Bioconductor进行基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选枳实薤白桂枝汤的有效成分61个,药物-疾病共同作用靶点104个;Cytoscape 3.7.1网络得到候选化合物47个,蛋白质-蛋白质相互作用(PPI)网络中核心基因为丝裂原活化蛋白激酶8(MAPK8)、淀粉样前体蛋白(APP)、表皮生长因子受体(EGFR),分子对接香蜂草苷、新橙皮苷、菠菜甾醇与核心靶点具有较强的亲和能力,涉及前列腺癌(prostate cancer)、乙型肝炎(Hepatitis B)、流体剪切力及动脉硬化(gluid shear stress and atherosclerosis)、糖尿病并发症中的糖化终末产物及其受体信号通路(AGE-RAGE signaling pathway in diabetic complications)等通路发挥治疗心血管疾病作用。结论:枳实薤白桂枝汤以多成分、多基因、多通路的复杂形式发挥其药效作用,为心血管疾病药物的开发提供理论依据。Objective: To explore the action mechanism of Zhishixiebaiguizhi decoction in the treatment of cardiovascular disease.Methods: TCMSP was used to screen the active ingredients of Zhishixiebaiguizhi decoction and target genes.The disease target genes were searched through OMIM and Genecards databases.The drug active ingredient targets were mapped to disease targets.Cytoscape3.7.1 was used to construct the drug-component-target-disease network to find the key components.STRING database was utilized to obtain protein interaction core genes and dock with the top three core genes.GO and KEGG pathway enrichment were performed by Bioconductor.Results: Totally 61 active ingredients of Zhishixiebaiguizhi decoction and 104 intersection genes were obtained.Moreover,47 candidate compounds were obtained by network of Cytoscape 3.7.1.Core targets were MAPK8,APP and EGFR screened out through PPI network,which had strong affinity to neohesperidin,spinach sterol and meringoside via molecular docking,and concluded prostate cancer,hepatitis B,fluid shear stress and atherosclerosis,and AGE-RAGE signaling pathway in diabetic complications to play roles in treating cardiovascular diseases.Conclusion: Zhishixiebaiguizhi decoction exhibits pharmacological effects in a complex form of multiple-component,multiple-gene and multiple-pathway,and the study provides theoretical basis for the development of drugs for cardiovascular diseases.

关 键 词：网络药理学 分子对接 心血管疾病 枳实薤白桂枝汤 作用机制 

分 类 号：R285[医药卫生—中药学]