天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (12): 2136-2145.doi: 10.16333/j.1001-6880.2021.12.018

• 数据研究 • 上一篇    下一篇

基于网络药理学及分子对接技术分析“半边莲-白花蛇舌草”药对治疗银屑病的作用机制

沈乐乐1,席建元2*,孙立新3,王子加3,刘均瑜3,李静3   

  1. 1宁夏医科大学,银川 750004;2湖南中医药大学第一附属医院,长沙 410000;3湖南中医药大学,长沙 410208
  • 出版日期:2021-12-28 发布日期:2021-12-30
  • 基金资助:
    湖南省教育厅重点项目(19A363)

Based on network pharmacology to analyze the mechanism of Lobeliae Chinensis Herba-Hedyotis Herba drug pair on the treatment of psoriasis

SHEN Le-le1,XI Jian-yuan2*,SUN Li-xin3,WANG Zi-jia3,LIU Jun-yu3,LI Jing3   

  1. 1Ningxia Medical University,Yinchuan 750004,China;2The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410000,China;3Hunan University of Chinese Medicine,Changsha 410208,China

  • Online:2021-12-28 Published:2021-12-30

摘要:

基于网络药理学及分子对接技术探讨“半边莲-白花蛇舌草”药对治疗银屑病的有效活性成分及作用机制。运用TCMSP数据库筛选“半边莲-白花蛇舌草”药对的活性成分及靶标,并通过GeneCards数据库获取银屑病疾病靶点,获取交集靶标,利用Cytoscape 3.6.1软件构建“药物-活性成分-靶点-疾病”网络图,利用STRING数据库构建PPI蛋白互作网络,并筛选出核心靶蛋白,对交集靶标进行GO生物过程及KEGG通路富集分析,最后利用SYBYL-X 21.1进行“半边莲-白花蛇舌草”药对与核心靶蛋白的模拟分子对接验证。从“半边莲-白花蛇舌草”中筛选获得24个活性成分,其中槲皮素、木犀草素、山奈酚、刺槐素、β-谷甾醇、环三烯酚为药对的关键活性成分,其作用主要涉及AKT1、JUN、MAPK1、RELA、HSP90AA1、IL6、ESR1、MAPK8、EGFR、MAPK14核心靶蛋白,GO与KEGG通路富集分析提示药对干预银屑病的生物学过程复杂多样,并且在PI3K-Akt信号通路、VEGF相关通路、Th1和Th2细胞、B细胞受体、HIF-1α等信号通路上基因富集性较高。在60个对接结果中,半数提示有较优的对接活性,槲皮素与核心靶蛋白结合情况最佳,HSP90AA1是半边莲-白花蛇舌草中关键化学成分结合活性最优的靶蛋白。“半边莲-白花蛇舌草”药对干预银屑病的机制具有多靶点、多途径的特点,与血管生成、炎性反应、免疫介导等途径关系密切,初步揭示了其作用的关键靶点及涉及的生物学过程和信号通路,为今后临床用药组方治疗银屑病以及实验研究提供理论依据。

关键词: 半边莲-白花蛇舌草, 银屑病, 作用机制, 网络药理学, 分子对接

Abstract:

In this study,network pharmacology and molecular docking technology were used to study the effective active components and mechanism of “Lobeliae Chinensis Herba-Hedyotis Herba” in the treatment of psoriasis.The TCMSP database was used to screen the active components and targets of the drug pair “Lobeliae Chinensis Herba-Hedyotis Herba”,and the psoriasis disease targets and intersection targets were obtained through the genecards database.The network diagram was constructed by using Cytoscape 3.6.1 software,the protein interaction network was constructed by using string database,and the core target proteins were screened,Gene Ontolog(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the intersection target.Finally,SYBYL-X 2.1.1 was used to verify the simulated molecular docking of “Lobeliae Chinensis Herba-Hedyotis Herba” with the core target protein.We screened and obtained 24 active components from “Lobeliae Chinensis Herba-Hedyotis Herba”,quercetin,luteolin,kaempferol,acacetin,β-sitosterol,and cycloeucalenol are the key active components of the drug pair,and their effects mainly involve the core target proteins of AKT1,JUN,MAPK1,RELA,HSP90AA1,IL6,ESR1,MAPK8,EGFR,MAPK14.The enrichment analysis of GO and KEGG pathways suggests that the biological process of drug intervention in psoriasis is complex and diverse,including PI3K-Akt signaling pathway,VEGF related pathway,Th1 and Th2 cells,B cell receptor and HIF-1α signaling pathway.Among the 60 docking results,half of them suggested that they had better docking activity.Quercetin had the best binding to the core target protein,and HSP90AA1 was the target protein with the best binding activity of the key chemical components in “Lobeliae Chinensis Herba-Hedyotis Herb”.The mechanism of “Lobeliae Chinensis Herba-Hedyotis Herba” on the intervention of psoriasis has the characteristics of multi-pathway and multi-channel,which is closely related to angiogenesis,inflammatory response,immune-mediated and other pathways.It preliminarily reveals the key targets of its action and the biological processes and signal pathways involved,so as to provide a theoretical basis for the treatment of psoriasis and experimental research in the future.

Key words: Lobeliae Chinensis Herba-Hedyotis Herba, psoriasis, mechanism, network pharmacology, molecular docking

中图分类号:  R275.9