摘要
目的:采用网络药理学方法探讨茯菟丹治疗糖尿病肾病(diabetic kidney disease,DKD)的作用机制。方法:依托中药系统药理学研究平台(TCMSP)、中药综合数据库(TCMID)、台湾@TCM检索茯菟丹全方6味中药相关的所有化学成分、作用靶点,进而构建化合物-靶点网络图;通过DrugBank,GAD,OMIM以及TTD寻找DKD相关的靶点。从String数据库中获得仅源于活性成分作用的靶点间交互作用的信息,导入Cytoscape3.6.1软件中进而构建部分中药靶点相互作用网络图;筛选药物靶点间交互作用图的核心靶点,利用ClueGO分别对核心靶点和共同靶点(中药作用靶点与DKD疾病相关靶点的交集靶点)进行KEGG通路富集分析。结果:选择口服利用度(OB)≥30%,类药性(DL)≥0.18作为活性成分的筛选条件,筛选出茯菟丹中的61个活性成分和224个相应靶点;获得DKD相关靶点109个,中药作用靶点与DKD疾病相关靶点存在25个共同靶点;通过构建"中药作用靶点-DKD疾病靶点交互作用网络",以自由中心度、介度中心度、接近中心度等网络拓扑参数筛选出茯菟丹治疗DKD的核心靶点63个,进一步通过KEGG进行通路富集分析,共同靶点富集得到21条条目,其中HIF-1 signaling pathway,IL-17 signaling pathway,TNF signaling pathway,Relaxin signaling pathway,AGE-RAGE signaling pathway in diabetic complications等5条是生物通路,关键靶点富集得到84条条目,其中有IL-17 signaling pathway,TNF signaling pathway,AGE-RAGE signaling pathway in diabetic complications,C-type lectin receptor signaling pathway,Toll-like receptor signaling pathway等27条是生物通路。结论:通过网络药理学验证了茯菟丹多成分、多靶点、整体调节的作用特点,预测了茯菟丹治疗DKD的主要作用机制,为其活性成分研究和实验研究提供理论依据。
Objective: To explore the active compounds and mechanism of Futu Pellet for diabetic kidney disease(DKD) based on network pharmacology. Methods: Chemical components and targets related to the six TCM herbs were searched through TCMSP, TCMID and TCM Database@Taiwan. Compound-target networks were constructed to explore the mechanism of Futu Pellet. Through DrugBank, GAD, OMIM and TTD, the targets of DKD were selected, and then the network diagram of disease-target interaction was constructed. Information data of the interaction between active ingredient targets were obtained from a protein interaction information database. The above information was imported into the Cytoscape 3.6.1 composition software to construct a visual network model of the interaction of the component-corresponding target-disease target. Then, the nuclear targets in the interaction diagram of drug targets were screened, ClueGO was used to carry out GO analysis of the nuclear targets, and KEGG database was used to carry on the related pathway enrichment of the nuclear targets. Results: Sixty-one active ingredients and 224 corresponding protein targets of Futu Pellet were screened with the criteria of oral bioavailability(OB)≥30% and drug likeness(DL)≥0.18, and 109 related targets of DKD were obtained. There were 25 common targets among the drug-targets and DKD disease-related targets. Through the evaluation of network topological characteristics, such as degree, closeness, and betweenness, 63 targets were selected to serve as the nuclear targets in DKD. The KEGG database was used for the enrichment of the selected targets, and 21 pathways were screened which had effect on DKD, including five biological process entries: HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Relaxin signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. In addition, another 84 pathways of core targets were also screened out, including 27 biological process entries such as IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway and so on. Conclusion: This study revealed the main active compounds and possible mechanism of Futu Pellet for treatment of DKD and verified the characteristics of multi-components, multi-targets, and integral regulation for Futu Pellet, predicting the main possible mechanism for the treatment of DKD, which provided theoretical basis for the study of active ingredients and experimental research.
作者
李晓朋
刘枚芳
刘旭生
张蕾
LI Xiao-peng;LIU Mei-fang;LIU Xu-sheng;ZHANG Lei(Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;Guangdong Provincial Hospital of Traditional Chinese Medicine,Guangzhou 510120,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第6期670-680,共11页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81603717)。
关键词
网络药理学
茯菟丹
糖尿病肾病
network pharmacology
Futu Pellet
diabetic kidney disease
