基于网络药理学的苦木——穿心莲药对抗胆汁淤积的机制研究  

Mechanism Prediction of Medicine Pair of Ramulus et Folium Picrasmae and Herba Andrographis Against Cholestasis Based on Network Pharmacology

作　　者：王美琪 林朝展[1] 祝晨蔯[1] WANG Meiqi;LIN Chaozhan;ZHU Chenchen(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510006,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《今日药学》2020年第7期453-461,473,共10页Pharmacy Today

基　　金：国家自然科学基金(81673872,81974520);广州中医药大学学科重点项目(2020-2022)。

摘　　要：目的通过网络药理学寻找并筛选苦木与穿心莲中重要的活性成分和作用靶点,通过靶点功能富集预测生物功能与作用通路,探讨苦木—穿心莲配伍抗胆汁淤积的分子机制。方法利用(中药系统药理学分析平台数据库)TCMSP等多个数据库联合检索并筛选穿心莲和苦木中的活性成分和靶点,同时在OMIM等数据库中搜索胆汁淤积相关的靶点,筛选出苦木和穿心莲抗胆汁淤积的潜在作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络,同时利用String数据库结合Cytoscape软件绘制蛋白互作网络,寻找药对配伍中起关键作用的活性成分和作用靶点。运用Cytoscape软件中Clue GO和Clue Pedia插件对作用靶点进行GO生物功能分析和KEGG通路富集,进一步预测苦木—穿心莲配伍抗胆汁淤积的机制。结果经过筛选,共得到穿心莲与苦木的31个活性成分,活性成分所对应的抗胆汁淤积潜在作用靶点共有37个。网络分析和靶点富集结果表明,作用靶点主要关联胆汁淤积疾病中的炎症、凋亡和氧化应激,参与调节ROS活性氧合成、氧化应激反应和鞘脂与脂质代谢等生物过程,同时对胆汁的分泌也具有一定的干预作用,涉及了NF-κB信号通路、IL-17信号通路和TNF信号通路,其中主要的作用靶点包括IL6、TNF、CASP3、MAPK1、PPAR、NFKB1、PARP1等。结论研究预测了苦木—穿心莲药对抗胆汁淤积的机制,体现了中药多成分、多靶点的作用特点,为苦木与穿心莲配伍治疗胆汁淤积性肝病的作用机制提供了理论依据。OBJECTIVE The significant active compounds and targets related to cholestasis in Herba andrographis and Ramulus et folium picrasmae was searched and screened on the basis of network pharmacology.And the molecular mechanism of those two herbs in the treatment of cholestasis was predicted by biological process and pathway enrichment based on the targets.METHODS The active compounds and targets were searched from online databases including TCMSP.And the potential targets against cholestasis in Herba andrographis and Ramulus et folium picrasmae was screened based on cholestasis targets acquired from OMIM and other online databases.The compounds-targets network and Protein-Protein interaction(PPI)network was constructed by Cytoscape to analyze significant active compounds and targets.The mechanism of the two herbs against cholestasis was further predicted explored based on GO biological process analysis and KEGG pathway enrichment by ClueGO and CluePedia.RESULTS 31 active compounds of Herba andrographis and Ramulus et folium picrasmae and 37 targets related to cholestasis was acquired from the screening.The network analysis and targets enrichment showed that the targets can regulate the process including inflammation,apoptosis and oxidative stress in cholestasis.The mechanism was involved in regulation of biological processes including reactive oxygen species biosynthetic process,regulation of cellular response to oxidative stress and lipid storage,as well as pathways including NF-kappa B signaling pathway,TNF signaling pathway,IL-17 signaling pathway,Sphingolipid signaling pathway and bile secretion.And IL6,TNF,CASP3,MAPK1,PPAR,NFKB1 and PARP1 were predicted as significant targets.CONCLUSION The study predicted and explored the mechanism of Herba andrographis and Ramulus et folium picrasmae against cholestasis based on network pharmacology.The networks reflected characteristics of multi-components,multi-targets,and multi-pathways of Traditional Chinese Medicine(TCM),which provided theory evidence for the research of

关 键 词：苦木—穿心莲药对 网络药理学 胆汁淤积 靶点 

分 类 号：R932[医药卫生—生药学]