Liu Nan, Jiang Yun-Yao, Huang Ting-Ting, Hou Jin-Cai, Liu Jian-Xun
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
Beijing Key Laboratory of Pharmacology of Chinese Materia Medica, Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Zhongguo Zhong Yao Za Zhi. 2018 Jun;43(11):2190-2198. doi: 10.19540/j.cnki.cjcmm.20180418.001.
The point of this study is to explore and investigate mechanisms of Buyang Huanwu decoction for treatment of cerebral infarction (CI) using a network pharmacology approach. First, TCMSP database, DrugBank database and PharmMapper server were used and combined with oral bioavailability and drug analysis to screen the components of Buyang Hanwu decoction and predict the potential targets. Then, Cytoscape 3.5.1 software was used to construct compounds-targets network and the protein-protein interaction (PPI) networks for targets of compounds and CI-related targets and merge the two PPI networks to acquire active targets. Finally, gene ontology (GO) and KEGG pathway analysis of active targets were carried out by DAVID online analysis tool and KOBAS 3.0 software. In total of 150 screened compounds and 232 potential targets were obtained. And in total of 208 active targets were finally determined by merging networks. Results indicated that Buyang Huanwu decoction might have a role in treating CI by regulating some biological processes including response to drug, aging, response to hypoxia, and blood coagulation, and some molecular function, such as protein binding, enzyme binding and serine-type endopeptidase activity. The mechanisms might be concerned with PI3K-Akt signaling pathway, TNF signaling pathway, HIF-1 signaling pathway and cAMP signaling pathway. Among them, the regulation of PI3K-Akt signaling pathway might be one of the most crucial mechanisms.
本研究旨在采用网络药理学方法探索和研究补阳还五汤治疗脑梗死（CI）的机制。首先，利用中药系统药理学数据库与分析平台（TCMSP数据库）、药物银行（DrugBank数据库）和中药靶点预测服务器（PharmMapper服务器），并结合口服生物利用度和药物分析筛选补阳还五汤的成分并预测潜在靶点。然后，使用Cytoscape 3.5.1软件构建化合物-靶点网络以及化合物靶点与CI相关靶点的蛋白质-蛋白质相互作用（PPI）网络，并将两个PPI网络合并以获得活性靶点。最后，通过DAVID在线分析工具和KEGG 3.0软件对活性靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。共获得150个筛选化合物和232个潜在靶点。通过网络合并最终确定了208个活性靶点。结果表明补阳还五汤可能通过调节一些生物学过程发挥治疗CI的作用，这些生物学过程包括对药物的反应、衰老、对缺氧的反应和血液凝固，以及一些分子功能，如蛋白质结合、酶结合和丝氨酸型内肽酶活性。其机制可能与磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路、肿瘤坏死因子（TNF）信号通路、缺氧诱导因子-1（HIF-1）信号通路和环磷酸腺苷（cAMP）信号通路有关。其中，PI3K-Akt信号通路的调节可能是最关键的机制之一。
