摘要
目的通过网络药理学和虚拟筛选技术探讨穿心莲治疗登革热的作用机制。方法基于TCMSP、PubChem、FAF-Drugs4、Pharmmapper数据库,筛选穿心莲中的活性成分和预测穿心莲成分的潜在靶点。利用虚拟筛选和分子对接方法分析穿心莲成分和CD209蛋白的相互作用关系。通过DisGeNET、Genecard、OMIM数据库获得人类登革热疾病靶点。利用Cytosacpe 3.6.0软件构建穿心莲成分-靶点网络、蛋白-蛋白相互作用(Protein-Protein interaction, PPI)网络,对网络进行拓扑结构分析,筛选出关键化合物和关键靶点。提取核心子网络,利用DAVID对核心子网络的靶点做基因本体(GO)分析和京都基因百科全书(KEGG)富集分析。结果虚拟筛选显示,穿心莲的5个成分与CD209可通过氢键结合形成稳定的构象。成分-靶点网络分析得到5种重要活性成分,其中新穿心莲内酯最为关键。核心子网络分析得到5个重要靶点。GO分析和KEGG富集分析显示核心子网络靶点与抗炎、调节免疫等多个生物学过程相关。结论穿心莲作用于CD209蛋白发挥抗病毒、抗炎、调节免疫等作用,穿心莲通过多成分、多靶点、多通路治疗登革热,以上结论有待进一步开展实验加以验证。
Objective This study aimed to explore the mechanism of Chuanxinlian(Andrographis Herba) to treat the dengue based on network pharmacology and virtual screening. Methods By searching TCMSP, PubChem, FAF-Drugs4 and Pharmmapper databases, the active compounds of Chuanxinlian(Andrographis Herba) were acquired and the targets of Chuanxinlian(Andrographis Herba) were predicted. The interaction among compounds of Chuanxinlian(Andrographis Herba) and CD209 protein was analyzed by virtual screening and molecular docking. Human dengue targets were obtained through DisGeNET, Genecards and OMIM databases. Then the compounds and targets network and protein-protein interaction(PPI) network were constructed and analyzed by Cytosacpe 3.6.0 software independently. The hub compounds and hub targets were screened. The core subnetwork was constructed. DAVID was used to analyze the GO function and KEGG enrichment of the targets in the core subnetwork. Result Virtual screening showed that five compounds of Chuanxinlian(Andrographis Herba) and CD209 could form stable conformations through hydrogen bond. Five important active compounds were obtained by analyzing the compounds and targets network. Neoandrographolide was the key compound. Five hub targets were acquired by analyzing the core subnetwork. GO analysis and KEGG enrichment analysis showed that the core subnetwork was related to anti-inflammatory and immunoregulatory process. Conclusion Chuanxinlian(Andrographis Herba) had antiviral, anti-inflammatory and immunoregulatory effects on CD209 protein. Chuanxinlian(Andrographis Herba) treated dengue through multi-component, multi-target and multi-path mechanism. This conclusion needed to be confirmed by experiments in the future.
作者
罗子清
刘云涛
张忠德
奚小土
LUO Ziqing;LIU Yuntao;ZHANG Zhongde;XI Xiaotu(The Second Clinical Medicine College,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;The Second Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;Key Laboratory of Traditional Chinese Medicine Emergency Research,Guangzhou 510405,Guangdong,China)
出处
《中华中医药学刊》
CAS
北大核心
2021年第5期86-89,I0022-I0025,共8页
Chinese Archives of Traditional Chinese Medicine
基金
国家“十三五”科技重大专项(2017ZX10305501-006)
广东省中医急症研究重点实验室项目(2017B030314176)
广东省中医院中医药科学技术研究专项(YK2013B2N04)。
关键词
穿心莲
登革热
网络药理学
虚拟筛选
分子对接
Chuanxinlian(Andrographis Herba)
dengue
network pharmacology
virtual screening
molecular docking
