Liu FengZhi, Zhao Qian, Liu Suxian, Xu Yingzhi, Zhou Dongrui, Gao Ying, Zhu Lingqun
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2020 Oct 31;2020:3236768. doi: 10.1155/2020/3236768. eCollection 2020.
Stroke is the second significant cause for death, with ischemic stroke (IS) being the main type threatening human being's health. (AT) is widely used in the treatment of Alzheimer disease, epilepsy, depression, and stroke, which leads to disorders of consciousness disease. However, the systemic mechanism of AT treating IS is unexplicit. This article is supposed to explain why AT has an effect on the treatment of IS in a comprehensive and systematic way by network pharmacology.
ADME (absorbed, distributed, metabolized, and excreted) is an important property for screening-related compounds in AT, which were screening out of TCMSP, TCMID, Chemistry Database, and literature from CNKI. Then, these targets related to screened compounds were predicted via Swiss Targets, when AT-related targets database was established. The gene targets related to IS were collected from DisGeNET and GeneCards. IS-AT is a common protein interactive network established by STRING Database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analysed by IS-AT common target genes. Cytoscape software was used to establish a visualized network for active compounds-core targets and core target proteins-proteins interactive network. Furthermore, we drew a signal pathway picture about its effect to reveal the basic mechanism of AT against IS systematically.
There were 53 active compounds screened from AT, inferring the main therapeutic substances as follows: bisasaricin, 3-cyclohexene-1-methanol-,,4-trimethyl,acetate, ,,-7,10,13-hexadecatrienal, hydroxyacoronene, nerolidol, galgravin, veraguensin, 2'-o-methyl isoliquiritigenin, gamma-asarone, and alpha-asarone. We obtained 398 related targets, 63 of which were the same as the IS-related genes from targets prediction. Except for GRM2, remaining 62 target genes have an interactive relation, respectively. The top 10 degree core target genes were IL6, TNF, IL1B, TLR4, NOS3, MAPK1, PTGS2, VEGFA, JUN, and MMP9. There were more than 20 terms of biological process, 7 terms of cellular components, and 14 terms of molecular function through GO enrichment analysis and 13 terms of signal pathway from KEGG enrichment analysis based on < 0.05.
AT had a therapeutic effect for ischemic via multicomponent, multitarget, and multisignal pathway, which provided a novel research aspect for AT against IS.
中风是第二大致死原因，缺血性中风（IS）是威胁人类健康的主要类型。细辛脑（AT）广泛用于治疗阿尔茨海默病、癫痫、抑郁症和中风等导致意识障碍的疾病。然而，AT治疗IS的系统机制尚不明确。本文旨在通过网络药理学全面系统地解释AT对IS治疗有效的原因。
药物代谢动力学（吸收、分布、代谢和排泄，ADME）是筛选AT中相关化合物的重要性质，这些化合物从中药系统药理学数据库（TCMSP）、中药整合数据库（TCMID）、化学数据库以及中国知网的文献中筛选得出。然后，通过瑞士靶点预测与筛选出的化合物相关的靶点，建立AT相关靶点数据库。从疾病基因数据库（DisGeNET）和基因卡片（GeneCards）收集与IS相关的基因靶点。IS-AT是由STRING数据库建立的常见蛋白质相互作用网络。通过IS-AT共同靶基因对基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集进行分析。使用Cytoscape软件建立活性化合物-核心靶点以及核心靶点蛋白-蛋白相互作用网络的可视化网络。此外，我们绘制了其作用的信号通路图，以系统地揭示AT对抗IS的基本机制。
从AT中筛选出53种活性化合物，推断主要治疗物质如下：双细辛醚、3-环己烯-1-甲醇-,,4-三甲基乙酸酯、,,,-7,10,13-十六碳三烯醛、羟基奥罗星、橙花叔醇、加拉格文、维拉古辛、2'-O-甲基异甘草素、γ-细辛醚和α-细辛醚。我们获得398个相关靶点，其中63个与靶点预测中的IS相关基因相同。除GRM2外，其余62个靶基因分别具有相互作用关系。前10位度的核心靶基因是IL6、TNF、IL1B、TLR4、NOS3、MAPK1、PTGS2、VEGFA、JUN和MMP9。基于<0.05，通过GO富集分析有超过20个生物过程术语、7个细胞成分术语和14个分子功能术语，通过KEGG富集分析有13个信号通路术语。
AT通过多成分、多靶点和多信号通路对缺血性疾病具有治疗作用，为AT对抗IS提供了新的研究方向。
