School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2018 Dec 17;2018:2582843. doi: 10.1155/2018/2582843. eCollection 2018.
Ischemic stroke is accompanied by high mortality and morbidity rates. At present, there is no effective clinical treatment. Alternatively, traditional Chinese medicine has been widely used in China and Japan for the treatment of ischemic stroke. Baicalin is a flavonoid extracted from Scutellaria baicalensis that has been shown to be effective against ischemic stroke; however, its mechanism has not been fully elucidated. Based on network pharmacology, we explored the potential mechanism of baicalin on a system level. After obtaining baicalin structural information from the PubChem database, an approach combined with literature mining and PharmMapper prediction was used to uncover baicalin targets. Ischemic stroke-related targets were gathered with the help of DrugBank, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). Protein-protein interaction (PPI) networks were constructed through the Cytoscape plugin BisoGenet and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. We obtained a total of 386 potential targets and 5 signaling pathways, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), hypoxia-inducible factor-1 (HIF-1), nuclear factor kappa B (NF-B), and forkhead box (FOXO) signaling pathways. GO analysis showed that these targets were associated with antiapoptosis, antioxidative stress, anti-inflammation, and other physiopathological processes that are involved in anti-ischemic stroke effects. In summary, the mechanism of baicalin against ischemic stroke involved multiple targets and signaling pathways. Our study provides a network pharmacology framework for future research on traditional Chinese medicine.
缺血性脑卒中具有较高的死亡率和发病率。目前，临床上缺乏有效的治疗方法。而中医药在我国和日本被广泛应用于缺血性脑卒中的治疗。黄芩苷是从黄芩中提取的一种黄酮类化合物，已被证明对缺血性脑卒中具有治疗作用，但作用机制尚未完全阐明。本研究基于网络药理学，从系统水平探讨黄芩苷治疗缺血性脑卒中的作用机制。从 PubChem 数据库中获取黄芩苷的结构信息，结合文献挖掘和 PharmMapper 预测方法，预测黄芩苷的作用靶点。借助 DrugBank、在线人类孟德尔遗传数据库（OMIM）、遗传关联数据库（GAD）和治疗靶点数据库（TTD）获取与缺血性脑卒中相关的靶点。利用 Cytoscape 插件 BisoGenet 构建蛋白-蛋白相互作用（PPI）网络，并采用拓扑分析方法进行分析。通过数据库检索，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。结果共获得 386 个潜在作用靶点和 5 条信号通路，涉及丝裂原活化蛋白激酶（MAPK）、磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）、缺氧诱导因子-1（HIF-1）、核因子 κB（NF-κB）和叉头框（FOXO）信号通路。GO 分析结果表明，这些靶点与抗细胞凋亡、抗氧化应激、抗炎等参与抗缺血性脑卒中的病理生理过程有关。综上所述，黄芩苷治疗缺血性脑卒中的作用机制涉及多个靶点和信号通路。本研究为进一步研究中药治疗缺血性脑卒中提供了网络药理学框架。
