摘要
目的 研究地锦草“清热解毒、凉血止血、利湿退黄”的物质基础与作用机制。方法 采用网络药理学方法,通过TCMSP、 SymMap、 CNKI、 PubMed筛选地锦草的活性成分;通过GeneCard、 TCMSP、SymMap、SwissTargetPrediction获取地锦草活性成分的作用靶标;利用SymMap将地锦草传统功效与现代疾病相关联,并通过GeneCard检索疾病对应靶标;利用STRING对地锦草成分-疾病交集靶标进行相互作用分析得到地锦草潜在靶标相互作用网络关联图;采用DAVID数据库对潜在靶标进行GO分析和KEGG信号通路富集分析;导入Cytoscape软件构建地锦草“功效-疾病-通路-靶标-活性成分”网络关联图。采用Autodock软件对关键活性成分和潜在靶标进行分子对接以验证网络分析结果的可靠性,并通过抗炎、凝血、抗肿瘤实验验证网络分析结果的准确性。结果 地锦草“清热解毒、凉血止血、利湿退黄”三种传统功效分别对应现代医学疾病中的痢疾、出血及黄疸。通过网络药理学研究,得到地锦草的潜在活性成分20个,治疗痢疾、出血及黄疸的潜在靶标分别有26、69、45个,富集于炎症、凝血、癌症相关通路。分子对接结果显示关键成分和靶标有较好的结合能力。体外实验结果显示,槲皮素、没食子酸、芹菜素具有很好的抗炎活性,槲皮素、没食子酸、木犀草素、芹菜素、鞣花酸具有较强的凝血活性,槲皮素、没食子酸、木犀草素、芹菜素具有较强的抗肿瘤活性,验证了网络药理学的部分预测结果。结论 基于地锦草传统功效“清热解毒、凉血止血、利湿退黄”,挖掘了其治疗现代疾病“痢疾、出血、黄疸”的“多成分-多靶点-多通路”的作用特点,初步揭示了地锦草的物质基础及作用机制,为地锦草的临床应用提供了科学依据。
Objective To explore the material basis and mechanism of action of Euphorbiae humifusae herba(EHH), which has the efficacy of “clearing heat and removing toxin, cooling blood and stopping bleeding,draining dampness to relieve jaundice.”Methods TCMSP,SymMap,CNKI,and PubMed were used to screen the active components of EHH. GeneCard, TCMSP, SymMap, and SwissTargetPrediction were used to obtain the targets of active components of EHH. SymMap was utlized to associate the traditional effects of EHH with modern diseases,and the corresponding targets of disease were retrieved from GeneCard. STRING was employed to analyze the intersection target of the components of EHH-disease,then the potential target interaction network of EHH was obtained. GO analysis and KEGG pathway enrichment were performed by using DAVID database, the above information was imported to Cytoscape to construct the “efficacy-disease-pathway-targets-active components”network map of EHH. The Autodock software was further used to perform molecular docking of key active components and potential targets to verify the reliability of the network analysis,and the accuracy of the network analysis was verified by anti-inflammatory,coagulation,and anti-tumor assays. Results The traditional efficacy of EHH, such as “clearing heat and removing toxin, cooling blood and stopping bleeding, draining dampness to relieve jaundice”corresponds to dysentery,hemorrhage,and jaundice in modern medicine,respectively. Through the network pharmacology research, we obtained 20 potential active components of EHH. There were also 26,69 and 45 potential targets for the treatment of dysentery, hemorrhage, and jaundice, respectively, which are enriched in inflammation,coagulation,and cancer-related pathways. The result of molecular docking showed that the active components and potential targets can combine well. In vitro experiments results showed that quercetin,gallic acid and apigenin have good anti-inflammatory activity. Quercetin,gallic acid,luteolin,apigenin and ellagic acid have strong coagulation activity. Moreover,quercetin,gallic acid,luteolin,and apigenin have strong antitumor activity. The above results verified some prediction of network pharmacology. Conclusion Based on the traditional efficacy of “clearing heat and removing toxin,cooling blood and stopping bleeding,draining dampness to relieve jaundice”,this study explored the “multi-component,multi-target and multi-pathway” characteristics of EHH for the treatment of dysentery,bleeding and jaundice,which not only preliminarily revealed the material basis and action mechanism of EHH,but also provided a scientific basis for the clinical application of EHH.
作者
曾晓涛
陈艳琰
乐世俊
黄昱曦
徐顶巧
付瑞嘉
唐于平
ZENG Xiaotao;CHEN Yanyan;YUE Shijun;HUANG Yuxi;XU Dingqiao;FU Ruijia;TANG Yuping(Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility,Shaanxi University of Chinese Medicine,Xi'an 712046 Shaanxi,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2022年第9期1205-1217,共13页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家重点研发计划项目(2019YFC1711000)
陕西省青年科技新星培育计划项目(2021KJXX-46)
陕西高校青年创新团队项目(2020)
陕西中医药大学学科创新团队项目(2019-YL10)。
关键词
地锦草
网络药理学
分子对接
实验验证
传统功效
活性成分
抗炎
凝血
抗肿瘤
Euphorbiae humifusae herba
network pharmacology
molecular docking
experimental verification
traditional efficacy
active components
anti-inflammatory
coagulation
anti-tumor
