网络药理学方法研究红花注射液主要活性成分对脑血管疾病网络的调控作用

A Network Pharmacology Based Study of Regulation Effects of the Main Active Components in Honghua Injection on Cerebrovascular Disease Network

目的运用网络药理学理念和网络分析技术研究红花注射液主要活性成分对脑血管疾病网络的调控作用。方法整合HPRD和BioGRID蛋白-蛋白相互作用关系,为网络构建提供基础。利用公共数据库RGD中脑血管疾病相关基因构建疾病网络。全面收集PubMed中红花注射液5个主要活性成分的靶点信息,提取成分-靶点关系,整合脑血管疾病网络构建成分-靶点网络。运用网络拓扑学属性分析、子簇聚类算法及网络GO富集分析,发现成分-靶点网络的关键靶点、生物学途径及成分之间的协同作用。结果成分-靶点网络含有940个节点,2 360条连接。MCODE分析得到28个子簇,其中节点数≥3的子簇有18个,对得分≥3的6个子簇开展BinGO分析,发现子簇涉及的生物学过程主要有生物大分子合成及代谢、神经再生、凋亡、血管生成、免疫炎症反应、缺氧应激响应等,其中羟基红花黄色素A和槲皮素可能通过协同抗凋亡的作用发挥抗脑血管疾病作用。结论本实验运用网络药理学方法和技术,从分子网络层面揭示了红花注射液主要活性成分抗脑血管疾病的多靶点、多途径作用模式及成分间存在的协同作用。

OBJECTIVE To investigate the regulation effects of main active components in Honghua Injection on cerebrovascular disease network. METHODS Cerebrovascular disease network was constructed using genes from public database RGD based on the protein-protein interaction （PPI） relationship databases HPRD and BioGRID. Then targets of five main active components in Honghua injection was retrieved from PubMed. Component-target relationships were extracted and associated with PPI in cerebrovascular disease. Component-target network was constructed with Cytoscape 3.1.0 . Network analysis technologies were applied to find eritieal targets, biological pathways and potential synergistic effects among components. RESULTS The component-target network contains 940 nodes and 2 360 edges. MCODE analysis extracted 28 clusters in which 18 clusters had at least 3 nodes. There were 6 clusters with score ≥ 3, and they were further investigated using BinGO analysis. The results showed that the main biological processes included regulation of macromolecule biosynthetic and metabolic processes, neurogenesis, apoptosis, angiogenesis, immune-inflammation reaction, response to hypoxia stress. Our study also indicated that Hydroxysafflor yellow A and Quercetin may show their cerebrovascular-protective potential based on their synergistic anti-apoptosis effects. CONCLUSION From the view of molecular network, our study applied network pharmacology methods and technologies to reveal the multi-target, multi-pathway mode of action of Honghua injection on anti-eerebrovascular disease effects, and the synergistic effects among Hydroxysafflor yellow A and quercetin.