药学学报, 2018, 53(9): 1422-1428
引用本文:
周荣荣, 张萌, 朱彦, 周文静, 李彦文, 李志勇. 含党参方剂的数据挖掘及防治胃肠道疾病的分子机制[J]. 药学学报, 2018, 53(9): 1422-1428.
ZHOU Rong-rong, ZHANG Meng, ZHU Yan, ZHOU Wen-jing, LI Yan-wen, LI Zhi-yong. Data mining of the prescription containing Codonopsis and study on the molecular mechanism of prevention and treatment of gastrointestinal disease[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1422-1428.

含党参方剂的数据挖掘及防治胃肠道疾病的分子机制
周荣荣1,4, 张萌2, 朱彦3, 周文静1, 李彦文3, 李志勇1,4,5
1. 山西中医药大学 基础医学院, 山西 晋中 030600;
2. 山西中医药大学 中药学院, 山西 晋中 030600;
3. 中国中医科学院中医药信息研究所, 北京 100700;
4. 中央民族大学药学院, 北京 100081;
5. 云南省中药新资源开发研究协同创新中心, 云南 昆明 650051
摘要:
基于数据挖掘工具分析含党参高频对药的用药规律,利用网络药理学方法预测防治胃肠疾病的分子作用机制。筛选含党参方剂,使用R语言关联规则对筛选方进行数据挖掘,筛选同时满足support≥0.3、confidence≥0.9的高频组合,利用中药整合药理学平台(TCMIP)预测高频对药的“中药-疾病”关键核心靶点,构建“中药-化合物-靶点-通路”网络,探究含党参高频对药在防治胃肠疾病中的分子作用机制。通过SystemsDock Web Site对成分与靶点进行分子对接验证。从543首含党参方剂数据中筛选得到185首标准方剂,关联分析获得含党参高频对药共6个,党参与当归、甘草、白术、茯苓、陈皮、黄芪密切相关;高频对药与补中益气汤(党参、当归、甘草、白术、陈皮、黄芪、柴胡、升麻)相似;整合药理学平台发现6组党参高频对药均与靶点POMC、OPRM1、CCR9、HTR2C有关;预测含党参高频对药防治胃肠疾病已知靶点(HTR2C、POMC、OPRM1、CCR9、OPRD1)和潜在药物作用靶点(GNB1、GCK、SDHD、SLC25A2、DHRS4)。Gene Ontology (GO)富集分析显示,其生物功能主要定位在线粒体、髓鞘,参与三羧酸循环、血小板活化、天门冬氨酸代谢等生物过程;KEGG通路富集分析显示,其疾病代谢通路主要与氨基酸代谢、能量代谢、内分泌代谢等有关。含党参高频对药在防治胃肠疾病中存在多个靶点与神经细胞密切相关,推测其可能通过脑-肠轴、神经内分泌系统来发挥治疗作用。
关键词:    党参      胃肠疾病      关联规则      整合药理学      分子机制     
Data mining of the prescription containing Codonopsis and study on the molecular mechanism of prevention and treatment of gastrointestinal disease
ZHOU Rong-rong1,4, ZHANG Meng2, ZHU Yan3, ZHOU Wen-jing1, LI Yan-wen3, LI Zhi-yong1,4,5
1. School of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong 030600, China;
2. College of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030600, China;
3. Institute of Information on Traditional Chinese Medicine of China Academy of Chinese Medical Sciences, Beijing 100700, China;
4. School of Pharmacy, Minzu University of China, Beijing 100081, China;
5. Collaborative Innovation Center for the Development of New Chinese Medicine Resources in Yunnan, Kunming 650051, China
Abstract:
The medication rules of high frequency herb-pairs containing Codonopsis pilosula (Dangshen) were analyzed with data mining tools, and the molecular mechanisms of these herb-pairs on the gastrointestinal diseases were predicted with the network pharmacology. The R language association rules were used to mine the high frequency herb-pairs from TCM formulae containing Dangshen, and these herb-pairs would be screened out, which satisfied the following requirements with support ≥ 0.3 and confidence ≥ 0.9 at the same time. Using the Integrated Pharmacology Platform of Traditional Chinese Medicine (TCMIP) to predict the key core targets of the high frequency herb-pairs, the network of Chinese medicine-compound-target-pathway related to Dangshen were built to explore the preventing and treating molecular mechanism on gastrointestinal diseases. At last, the relation of the main active components from Dangshen and its herbal pairs with target proteins were validated by Systems Dock Web Site. The 185 formulae were selected from 543 formulae containing Dangshen, and 6 herbal pairs with Dangshen, which includes Angelica (Danggui), Licorice (Gancao), Atractylodes macrocephala (Baizhu), Poria cocos (Fuling), dried tangerine peel (Chenpi) and Astragalus membranaceus (Huangqi), were discovered with Apriori algorithm. The combination of 6 herbal pairs is similar to Bu Zhong Yi Qi Decoction; 6 herbal pairs with Dangshen were related to the target of POMC, OPRM1, CCR9 and HTR2C in TCMIP. The known targets (HTR2C, POMC, OPRM1, CCR9, OPRD1) and potential drug-targets (GNB1, GCK, SDHD, SLC25A2, DHRS4) for gastrointestinal diseases were predicted about the high frequency pairs with Dangshen. The results of GO enrichment analysis showed that the biological function was mainly located in the mitochondria and myelin sheath, and involved in the biological processes of three carboxylic acid cycle, platelet activation, and aspartic acid metabolism. KEGG pathway enrichment analysis showed that the main metabolic pathways related with Dangshen pairs involved amino acid metabolism, energy metabolism and endocrine metabolism. The prediction results showed many targets of the frequency herbal pairs with Dangshen preventing and treating gastrointestinal diseases were related with nerve cells. These herbal pairs could prevent and treat the gastrointestinal diseases through the neuroendocrine system and the brain gut axis.
Key words:    Codonopsis pilosula (Dangshen)    gastrointestinal disease    association rule    integrated pharmacology    molecular mechanism   
收稿日期: 2018-05-25
DOI: 10.16438/j.0513-4870.2018-0488
基金项目: 国家自然科学基金面上项目(81473797);云南省科重大科技专项计划资助项目(2017ZF004);北京市自然科学基金资助项目(7174328).
通讯作者: 李志勇,Tel:86-10-68939935,E-mail:lizhiyong@muc.edu.cn
Email: lizhiyong@muc.edu.cn
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