天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (9): 1573-1581.doi: 10.16333/j.1001-6880.2022.9.015

• 数据研究 • 上一篇    下一篇

基于网络药理学、分子对接及大鼠实验的黄芪-冬虫夏草药对治疗IgA肾病作用机制研究

傅   奕1,2,陈帮明1,李鑫2,3,4*,付   义1,伍宏泽1,刘永芳1   

  1. 1江西省中医肾病临床医学研究中心九江市中医院,九江 332000;2湖南中医药大学;3湖南中医药大学中医诊断学湖南省重点实验室;4湖南中医药大学中医心肺病证辨证与药膳食疗湖南省重点研究室,长沙 410208
  • 出版日期:2022-09-28 发布日期:2022-10-09
  • 基金资助:
    国家自然科学基金委员会地区科学基金(82060839);江西省卫生健康委科技计划(20204305);江西省中医药科研计划(2019A395)

The mechanism of Astragali Radix-Cordyceps on the treatment of IgA nephropathy based on network pharmacology, molecular docking and rat experiments 

FU Yi1,2,CHEN Bang-ming1,LI Xin2,3,4*,FU Yi1,WU Hong-ze1,LIU Yong-fang1   

  1. 1Jiujiang Hospital of Traditional Chinese Medicine,Jiangxi Provincial Traditional Chinese Medicine Nephropathy Clinical Research Center,Jiujiang 332000,China;2Hunan University of Traditional Chinese Medicine;3Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics,Hunan University of Traditional Chinese Medicine;4Hunan Provincial Key Laboratory of TCM Cardiopulmonary Disease Syndrome Differentiation and Medicinal Diet Therapy,Hunan University of Traditional Chinese Medicine,Changsha 410208,China
  • Online:2022-09-28 Published:2022-10-09

摘要:

通过网络药理学筛选黄芪-冬虫夏草治疗IgA肾病(IgA nephropathy,IgAN)的作用靶点和相关信号通路,明确其作用机制,并进行实验验证。应用TCMSP、BATMAN-TCM数据库结合文献挖掘获取黄芪-冬虫夏草的活性成分和作用靶点;通过GeneCards、OMIM数据库获取慢性IgAN的疾病靶点;筛选出与黄芪-冬虫夏草共同的靶点,进而利用Venny 2.1绘制共同靶点韦恩图;利用STRING构建共同靶点互作网络(PPI);应用Cytoscape 3.7.1软件构建成黄芪-冬虫夏草丸活性成分-靶点交集的网络;通过R语言软件对共同靶点进行GO分析和慢性IgA肾病作用靶点的KEGG分析,筛选出潜在通路并分析其作用机制。运用分子对接技术验证黄芪-冬虫夏草活性成分与关键靶点的结合效能。取IgA肾病造模大鼠(分空白组、模型组和黄芪-冬虫夏草中剂量组)分别治疗21天。取肾脏组织,采用酶联免疫法检测各组大鼠肾组织中VEGFA含量。筛选出黄芪-冬虫夏草中生物活性成分5个,作用于37个IgAN的共同靶点,核心靶点为VEGFA、HIF1A、NOS3、CASP3,主要涉及类固醇结合、细胞凋亡过程的半胱氨酸型内肽酶活性、雌激素受体结合、胆固醇结合等生物过程,主要富集在Lipid and atherosclerosis信号通路、AGE-RAGE信号通路、Fluid shear stress and atherosclerosis通路、PI3K-Akt信号通路等信号通路。分子显示主要成分和关键靶点之间具有较好的结合效能。相对于模型组,黄芪-冬虫夏草中剂量组VEGFA含量显著降低(P<0.05)。黄芪-冬虫夏草药对可能作用于VEGFA、HIF1A、NOS3、CASP3等关键靶点,通过抑制纤维化等与IgA肾病疾病相关的信号通路实现对IgA肾病的治疗作用。

关键词: 网络药理学, 分子对接, 大鼠实验, 黄芪-冬虫夏草, IgA肾病, 作用机制

Abstract:

To screen the targets and related signaling pathways of Astragali Radix-Cordyceps in the treatment of IgA nephropathy (IgAN) by network pharmacology,to clarify its mechanism of action,and to verify it experimentally.TCMSP and BATMAN-TCM databases combined with literature mining were used to obtain the active components and targets of Astragali Radix-Cordyceps;the disease targets of chronic IgAN were obtained through GeneCards and OMIM databases;Venny 2.1 was used to draw a Venn diagram of common targets;STRING was used to build a common target interaction network (PPI);Cytoscape 3.7.1 software was used to build an interaction network of Astragali Radix-Cordyceps pills-target;through R language software GO analysis of common targets and KEGG analysis of chronic IgA nephropathy targets were performed to screen out potential pathways and their mechanisms of action were analyzed.Molecular docking technology was used to verify the binding efficacy of the active components of Astragali Radix-Cordyceps and key targets.IgA nephropathy model rats (model group and Astragali Radix-Cordyceps dose group with high,medium and low doses) were taken for 21 days,respectively,and the kidney tissue was collected to detect the expression of VEGFA protein in the kidney tissue of the rats in each group by Western blot.Five bioactive components were screened out from Astragali Radix-Cordyceps,which acted on 37 common targets of IgAN.The core targets were VEGFA,HIF1A,NOS3,and CASP3,which mainly involved cysteine-type steroid binding and apoptosis,endopeptidase activity,estrogen receptor binding,cholesterol binding and other biological processes are mainly enriched in lipid and atherosclerosis signaling pathway,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis pathway,PI3K-Akt signaling pathway and other signaling pathways.The molecules showed good binding potency between the main components and key targets.Compared with model group,the expression of VEGFA in the high and low dose groups of Astragali Radix-Cordyceps decreased (P<0.05),and there was no significant difference between the high-dose group and the middle-dose group (P> 0.05).Astragali Radix-Cordyceps may act on key targets such as VEGFA,HIF1A,NOS3,and CASP3,and achieve therapeutic effects on IgA nephropathy through fibrosis and other signaling pathways.

Key words: network pharmacology, molecular docking, rat experiment, Astragali Radix-Cordyceps, IgA nephropathy, mechanism of action

中图分类号:  R256.5