主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2019, Vol. 42 ›› Issue (12): 1006-1015.doi: 10.3969/j.issn.1006-2157.2019.12.007

• 中药药理 • 上一篇    下一篇

基于网络药理学与分子对接方法探讨昆明山海棠的毒性机制*

张丹1, 董一珠1, 吕锦涛1, 张晓朦1, 林志健1, 张冰1,2#   

  1. 1 北京中医药大学中药学院 北京 102488;
    2 北京中医药大学中药药物警戒与合理用药研究中心
  • 收稿日期:2019-06-30 出版日期:2019-12-30 发布日期:2020-01-06
  • 通讯作者: 张冰,女,博士,教授,主任医师,博士生导师,主要研究方向:中药药物警戒与合理用药研究、中药防治代谢性疾病研究,E-mail:zhangbing@bucm.edu.cn
  • 作者简介:张丹,女,在读博士生
  • 基金资助:
    *国家自然科学基金项目(No.81874349),北京中医药大学新教师启动基金项目(No.2019-JYB-XJSJJ007),北京中医药大学自主课题项目 (No.2019-JYB-XS-072),中医药传承与创新“百千万”人才工程(歧黄工程)歧黄学者项目

Prediction of toxicity mechanism of Kunming shanhaitang based on network pharmacology and with molecular docking*

Zhang Dan1, Dong Yizhu1, Lyu Jintao1, Zhang Xiaomeng1, Lin Zhijian1, Zhang Bing1, 2#   

  1. 1 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China;
    2 Center for Pharmacovigilance and Rational Use of Chinese Herbal Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
  • Received:2019-06-30 Online:2019-12-30 Published:2020-01-06
  • Contact: Prof. Zhang Bing, Ph.D., Doctoral Supervisor. Beijing University of Chinese Medicine. Liangxiang Town, Fangshan District, Beijing 102488. E-mail:zhangb@bucm.edu.cn

摘要: 目的 利用网络药理学结合分子对接技术探讨昆明山海棠引起不良反应的毒性机制。方法 系统检索昆明山海棠文献,全面筛选其活性成分并汇总相关不良反应,通过中药系统药理学数据库与分析平台、Swiss数据库以及STITCH数据库预测昆明山海棠活性成分-作用靶点,利用美国比较毒理基因组学数据库建立不良反应-作用靶点。合并获得交集基因,将相关毒性潜在靶点导入STRING数据库获取蛋白相互作用,利用DAVID平台进行GO生物功能过程和KEGG代谢通路富集分析。利用Systems Dock平台将昆明山海棠的特征性成分与关键毒性靶点进行分子对接。结果 筛选得到21个昆明山海棠的生物活性成分,通过构建毒性蛋白相互作用关系(PPI)网络获取相关毒性靶点47个。对毒性靶点PPI网络的富集分析结果显示,昆明山海棠的毒性靶点可能与p53信号通路、PI3K-Akt信号通路等密切相关。分子对接研究证实昆明山海棠中大多数活性成分与毒性靶点有着较好的结合活性。结论 初步验证了昆明山海棠引起不良反应的毒性机制,为进一步开展毒性中药致不良反应的作用机制研究提供了新思路和新方法。

关键词: 网络药理学, 分子对接, 昆明山海棠, 靶点, 毒性机制

Abstract: Objective To explore the potential toxicity mechanism of Kunming shanhaitang(Tripterygium Hypoglaucum Toot, Radix Tripterygium Hypoglaucum) with Methods of network pharmacology and molecular docking. Methods Literature on Kunming shanhaitang was first comprehensively searched to identify and collect its active ingredients and adverse drug reactions (ADRs), respectively. Targets of the active ingredients were then predicted with TCMSP, Swiss, and STITCH databases. Moreover, targets of ADRs were gathered through CTD database. Next, the common genes shared by the above two types of targets were submitted to STRING to obtain protein-protein interaction. In addition, GO biological function process and KEGG pathway enrichment analysis were conducted on DAVID platform. Finally, molecular docking was carried out between characteristic ingredients of the herb and its key toxicity targets with systemsDock Web Site. Results A total of 21 ingredient candidates of Kunming shanhaitang involving 47 toxicity targets were identified by establishing toxic protein-protein interaction(PPI) network. PPI network enrichment analysis of the toxicity targets showed that such targets were probably closely associated with the p53 signaling pathway, PI3K-Akt signaling pathway and some other pathways. According to the Results of molecular docking, the majority of the active ingredients in the medicinal herb enjoyed good binding activities with the toxicity targets. Conclusion This research verified preliminarily the toxicity mechanism of Kunming shanhaitang, providing new ideas and Methods for further research on the toxicity mechanism of ADRs of Chinese medicinal herbs with toxicity.

Key words: network pharmacology, molecular docking, Kunming shanhaitang, targets, toxicity mechanism

中图分类号: 

  • R285.5