摘要
目的采用网络药理学方法探讨赤芍治疗动脉粥样硬化(AS)的物质基础和作用机制。方法借助中药系统药理学分析平台(TCMSP)检索赤芍的化学成分和作用靶点;在人类基因数据库(GeneCards)、人类孟德尔遗传数据库(OMIM)中搜索AS靶点;使用String数据库构建蛋白质-蛋白质相互作用网络,并利用DisGeNET数据库对作用靶点类型进行归属;采用Cytoscape 3.7.1软件构建赤芍-活性成分-抗动脉粥样硬化靶点网络;利用Metascape平台对靶基因进行基因功能注释(GO)和京都基因和基因组百科全书(KEGG)通路分析。结果通过口服生物利用度(OB)和生物活性分子的类药性(DL)参数筛选得到赤芍29个潜在活性成分,共涉及41个作用靶点,与疾病靶点有关的活性成分有12个,与疾病有关的靶点有36个。主要通过调控细胞凋亡、白介素-17(IL-17)信号通路、流体剪切应力(FSS)与AS、缺氧诱导因子-1(HIF-1)信号通路、Th17细胞分化、肿瘤坏死因子(TNF)信号通路、甲状腺激素信号通路、p53信号通路、Toll样受体(TLR4)信号通路及磷酸肌醇3-激酶(PI3K)-Akt信号通路等多种途径发挥抗AS作用。结论网络药理学分析显示,赤芍通过多成分、多靶点、受途径共同发挥抗AS作用,有助于进一步了解赤芍的药理学作用机制,证实了网络药理学方法可以作为从整体角度揭示中医药作用机制的有效工具。
Objective To explore the material basis and mechanism of Radix Paeoniae Rubra in the treatment of atherosclerosis(AS).Methods The chemical composition and target of Radix Paeoniae Rubra were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),as the targets were searched in gene databases(GeneCards)and Online Mendelian Inheritance in Man(OMIM),protein-protein interaction network was constructed by String database,and the types of targets were classified by DisGeNET database.The network of Radix Paeoniae Rubra-active component-anti atherosclerotic target was constructed by the software of Cytoscape 3.7.1.The target genes were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)on Metascape.Results Twenty-nine potential active components of Radix Paeoniae Rubra were screened by oral bioavailability(OB)and drug-like(DL)parameters,involving 41 action targets,12 active components related to disease targets and 36 disease targets.Radix Paeoniae Rubra played the role of anti AS mainly through regulating apoptosis,interleukin-17(IL-17)signaling pathway,fluid shear stress(FSS)and AS,hypoxia inducible factor-1(HIF-1)signaling pathway,Th17 cell differentiation,tumor necrosis factor(TNF)signaling pathway,thyroid hormone signaling pathway,p53 signaling pathway,toll like receptor(TLR4)signaling pathway,PI3K Akt signaling pathway,and many other ways.Conclusion This study analyzes the molecular mechanism of Radix Paeoniae Rubra in the treatment of AS based on the network pharmacology,which is helpful to further understand the pharmacological mechanism of Radix Paeoniae Rubra,and confirms that the network pharmacology method can be an effective tool to reveal the mechanism of Chinese medicine from an overall perspective.
作者
王心意
鞠建庆
田园硕
樊懿萱
徐浩
WANG Xinyi;JU Jianqing;TIAN Yuanshuo;FAN Yixuan;XU Hao(Beijing University of Chinese Medicine,Beijing 100029,China,Cardiovascular Disease Center,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China,National Clinical Research Center for Chinese Medicine Cardiology,Beijing 100091,China)
出处
《中西医结合心脑血管病杂志》
2020年第6期865-873,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金资助项目(No.81874412)
北京市自然科学基金资助项目(No.7192185)。
关键词
动脉粥样硬化
赤芍
网络药理学
机制
atherosclerosis
Radix Paeoniae Rubra
network pharmacology
mechanism
