Shen Hong-Bo, Zhou Yi-Nong, Zheng Jie, Zhu Ruo-Hai
Deparment of Hepatobiliary Surgery, Quzhou People's Hospital Quzhou 324000, China.
Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(7):1464-1474. doi: 10.19540/j.cnki.cjcmm.20181214.003.
To predict the targets of active ingredients of Kuihua Hugan Tablets by network pharmacology, and explore the "multi-component-multi-target-multi-pathway" hepatoprotective mechanism of action. First, through traditional Chinese medicine systems pharmacology(TCMSP) and TCM Database@Taiwan Database, main active ingredients of Kuihua Hugan Tablets were screened out based on oral bioavailability(OB), drug-likeness(DL) and effective half-lives(HL). The targets of active ingredients of Kuihua Hugan Tablets were predicted based on the PharmMapper method. Then, the prediction was conducted by screening the target genes associated with chronic hepatitis and early cirrhosis through CooLGeN and GeneCards databases. Target gene functions and signal pathways were analyzed by bioinformatics annotation database Metascape. Cytoscape software was used to construct the Kuihua Hugan Tablets ingredient-target and ingredient-target-pathway network. String database combined with Cytoscape software was used to construct the networks of component-target and component-target-pathway. STRING database was combined with Cytoscape software to draw protein-protein interaction(PPI) network and conduct network topology analysis. Finally, Systems Dock Web Site software was applied in verifying the molecular docking between active ingredients and potential protein targets. A total of 26 compounds and 509 potential targets were screened out from Kuihua Hugan Tablets in the experiment. The results of PPI network analysis indicated that albumin(ALB), insulin-like growth factor 1(IGF1), matrix metalloproteinase-9(MMP9), matrix metalloproteinase-2(MMP2), non-receptor tyrosine kinase proto-oncogene(SRC), estrogen receptor 1(ESR1) and cancer-signal transduction-inflammation-drugs metabolism-related biological processes and metabolic pathways were closely associated with the active ingredients in Kuihua Hugan Tablets. The effects of Kuihua Hugan Tablets in alleviating chronic hepatitis and early cirrhosis indicated the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicines, providing new ideas for further research and development of Kuihua Hugan Tablets.
运用网络药理学预测葵花护肝片活性成分的作用靶点,探讨其“多成分-多靶点-多途径”的保肝作用机制。首先,通过中药系统药理学数据库(TCMSP)和台湾中医药数据库,基于口服生物利用度(OB)、类药性(DL)和有效半衰期(HL)筛选出葵花护肝片的主要活性成分。基于PharmMapper方法预测葵花护肝片活性成分的靶点。然后,通过CooLGeN和GeneCards数据库筛选与慢性肝炎和早期肝硬化相关的靶基因进行预测。利用生物信息学注释数据库Metascape分析靶基因功能和信号通路。运用Cytoscape软件构建葵花护肝片成分-靶点及成分-靶点-通路网络。结合STRING数据库与Cytoscape软件构建成分-靶点和成分-靶点-通路网络。利用STRING数据库与Cytoscape软件绘制蛋白质-蛋白质相互作用(PPI)网络并进行网络拓扑分析。最后,应用Systems Dock网站软件验证活性成分与潜在蛋白质靶点之间的分子对接。实验共从葵花护肝片中筛选出26种化合物和509个潜在靶点。PPI网络分析结果表明,白蛋白(ALB)、胰岛素样生长因子1(IGF1)、基质金属蛋白酶-9(MMP9)、基质金属蛋白酶-2(MMP2)、非受体酪氨酸激酶原癌基因(SRC)、雌激素受体1(ESR1)以及癌症信号转导-炎症-药物代谢相关的生物学过程和代谢途径与葵花护肝片中的活性成分密切相关。葵花护肝片在缓解慢性肝炎和早期肝硬化方面的作用表明了中药的多成分、多靶点和多途径特点,为葵花护肝片的进一步研发提供了新思路。