基于网络药理学的中药复方知柏地黄丸治疗代谢综合征的机制研究

目的:应用网络药理学的研究方法挖掘中药复方知柏地黄丸治疗代谢综合征的物质基础及其作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库检索中药复方知柏地黄丸中八味中药的主要活性成分,并进行靶点预测。通过OMIM、TTD、DisGeNET数据库检索代谢综合征的相关靶点,将中药靶点与疾病靶点取交集得到共同作用靶点。应用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络,通过Cytoscape软件对其进行拓扑学分析筛选出核心靶点。最后,基于Metascape软件并进行GO-BP生物功能富集和KEGG通路分析。结果:经数据库分析中药复方知柏地黄丸中含有活性化合物74个,作用靶点906个,其中290个为与代谢综合征共有靶点;通过对共有靶点的拓扑分析,筛选出核心靶点78个,GO-BP生物功能富集以及KEGG通路分析发现,其可通过循环系统、G蛋白偶联受体信号通路、脂多糖调节、调控血压、脂质代谢调节等多种生物学功能以及血管内皮生长因子信号通路、钙信号通路、ErbB信号通路等多条代谢通路发挥其治疗作用。结论:中药复方知柏地黄丸可通过过氧化物酶体增殖激活受体(PPAR)、转录激活因子-3(STAT3)、磷脂酰肌醇激酶(PIK3)等靶点经过循环系统、G蛋白偶联受体信号通路、与环状核苷酸第二信使偶联以及VEGF信号通路、钙信号通路、ErbB信号通路等代谢通路发挥治疗代谢综合征的作用,为其临床和基础研究提供新的科学依据。

Study on the Mechanism of Chinese Medicine Zhibai Dihuang Pill in the Treatment of Metabolic Syndrome Based on Network Pharmacology

To explore the material basis and mechanism of Chinese compound Zhibai Dihuang Pill in the treatment of metabolic syndrome by the application of network pharmacology research methods.Methods:Through the Chinese Medicine System Pharmacology Technology Platform (TCMSP) database,the main active components of traditional Chinese medicine compound Rhizoma Anemarrhenae,Cortex Phellodendri,Radix Rehmanniae Preparata,Fructus Corni,Rhizoma Dioscoreae,Cortex Moutan Radicis,Rhizoma Alismatis were retrieved and made for target prediction.The OMIM,TTD,and DisGeNET databases were used to retrieve the relevant disease targets of the metabolic syndrome,and the eight-flavored Chinese medicine target was intersected with the disease target to screen for a common target.The STRING platform was used to construct a protein-protein interaction(PPI) network model,and the network was topologically analyzed by using Cytoscape software to obtain the core target.GO-BP biofunctional enrichment analysis and KEGG pathway analysis were performed on the core targets by Metascape software.Results:By database analysis,it was inferred that the database of Chinese medicine compound Zhibai Dihuang Pill contained 74 active compounds,906 target sites,and 290 targets shared with metabolic syndrome.Through the topological analysis of common targets,the core of Chinese medicine compound Zhibai Dihuang Pill was screened for 78 target.From GO-BP biological function enrichment and KEGG pathway analysis,it was found that through the circulatory system,G protein coupled receptor signaling pathway,lipopolysaccharide regulation,regulation of blood pressure,lipid metabolism regulation and other biological functions,and a variety of metabolic pathways such as calcium signaling pathway,VEGF signaling pathway and ErbB signaling pathway they played a therapeutic role.Conclusion:This study explored the material basis and mechanism of Chinese medicine compound Zhibai Dihuang Pill in the treatment of metabolic syndrome,and provided a new scientific basis for its clinical and basic research.