摘要
目的运用网络药理学和分子对接技术探究黄芪-白术配伍治疗慢性阻塞性肺疾病的作用机制和药效物质。方法运用中药系统药理学分析平台(TCMSP)和GeneCards数据库,进行黄芪-白术药物成分和疾病所作用靶点收集,处理构建出化学成分-疾病靶标,筛选核心靶标。借助Metascape数据库进行GO注释和KEGG通路富集分析,将靶标映射至对应生物学信号通路,构建黄芪白术-化学成分、化学成分-核心靶点-COPD疾病等多层次网络关联图,筛选出药物活性成分和核心靶点。利用分子对接技术分析活性成分和核心靶点的相互作用关系,并采取体外抗炎活性实验进行验证。结果搜集到黄芪-白术中关键活性物质6个,潜在治疗COPD靶标131个,筛选出核心靶标16个。通过KEGG分析主要通过癌症信号通路(Pathways in cancer)、MAPK信号通路(MAPK signaling pathway),IL-17信号通路(IL-17 signaling pathway)通路发挥药效作用。分子对接结果显示,槲皮素、山奈酚、异鼠李素、8β-乙氧基苍术内酯Ⅲ、7-O-甲基异丁香酚等活性物质与COPD关键靶点之间具有较高的结合活性。体外抗炎活性验证槲皮素与山奈酚具有较好抗炎效果。结论本研究运用网络药理学和分子对接技术预测黄芪-白术治疗COPD作用机制,初步揭示了黄芪-白术配伍通过抑制炎症反应、调节上皮细胞生长增强保护屏障、抑制肿瘤血管生成等作用而发挥防治COPD的作用。研究结果预测了黄芪-白术配伍治疗COPD多基因和多途径的调节作用,可为临床合理用药及作用机制的研究提供参考。
Objective To explore the mechanism and pharmacodynamics of Radix Astragali seu Hedysari and Rhizoma Atractylodis Macrocephalae in the treatment of chronic obstructive pulmonary disease(COPD) by using network pharmacology and molecular docking techniques. Methods The systemic pharmacology analysis platform(TCMSP) and GeneCards database were used to collect the drug components and disease targets of Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae macrocosm, and then constructed the chemical components and disease targets and screened the core targets. With the help of Metascape database, GO annotation and KEGG pathway enrichment analysis,targets were mapped to the corresponding biological signal pathway, and multi-level network association maps such as Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae-chemical components, chemical components-core targets-COPD disease were constructed to screen out the active components and core targets of drugs. Molecular docking technique was used to analyze the interaction between active components and core targets. Then A549 cells induced by TNF-α were employed to test the predict results. Results A total of 131 disease targets were obtained from the 6 active components of Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae, and 16 core targets were selected. KEGG analysis showed that the Pathways in cancer, MAPK signaling pathway(MAPK signaling pathway), and IL-17 signaling pathway(IL-17 signaling pathway) played a pharmacological role. Molecular docking, according to the results of quercetin, kaempferol, isorhamnetin, 8β-ethoxy atractylenolide Ⅲ, 7-O-methylisomucronulatol between active material and the key targets for COPD has good affinity. Quercetin and kaempferol have good anti-inflammatory effects in vitro. Conclusion This study used network pharmacology and molecular docking technology to predict the action mechanism of Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae in the treatment of COPD, and preliminarily revealed the role of Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae compatibility in the prevention and treatment of COPD by inhibiting inflammatory response, regulating the growth of epithelial cells to enhance the protective barrier, and inhibiting tumor angiogenesis. The results predicted the regulatory effects of multiple genes and multiple pathways in the treatment of COPD by the combination of Radix Astragali seu Hedysari-Rhizoma Atractylodis Macrocephalae macrocosm, which could provide references for the research on rational drug use and the mechanism of action in clinical practice.
作者
朱泓锦
王佩阳
田燕歌
万焱
刘学芳
冯素香
Zhu Hongjin;Wang Peiyang;Tian Yange;Wan Yan;Liu xuefang;Feng Suxiang(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center for the Prevention and Treatment of Respiratory Diseases by Provinces and Ministries,Zhengzhou 450046,China;NMPA Key Laboratory for Quality Control and Evaluation of Traditional Chinese Medicine,Zhengzhou 450046,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第7期2206-2215,共10页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
河南省教育厅河南省高等学校重点科研项目(20A360007):基于网络药理学融合体内动态化学成分表征的补肺健脾方治疗慢性阻塞性肺疾病物质基础研究,负责人:刘学芳。
关键词
黄芪-白术
慢性阻塞性肺疾病
网络药理学
分子对接
作用机制
Radix Astragali seu Hedysari
Rhizoma Atractylodis Macrocephalae
Chronic obstructive pulmonary disease
Network pharmacology
Molecular docking
Mechanism of action
