基于网络药理学预测西瓜皮营养成分防治糖尿病作用机制的研究

Prediction of Therapeutic Mechanism of Nutritional Components from Watermelon Peel on Diabetes Mellitus Based on Network Pharmacology

目的运用网络药理学的方法,探讨西瓜皮营养成分防治糖尿病潜在的分子作用机制。方法首先通过查阅相关文献(CNKI、PubMed)及结合TCMSP、PubChem等数据库,以药效活性或ADME参数为指标,筛选西瓜皮的活性营养成分,其次通过BATMAN-TCM数据库、中药靶标数据库、HIT和TTD数据库,筛选西瓜皮营养成分防治糖尿病的潜在作用靶点,建立靶点数据集;利用OMIM数据库筛选糖尿病相关的靶标;利用PPI数据库构建西瓜皮和糖尿病作用的交互靶标;并用Cytoscape软件构建"药物成分-靶点-疾病"复杂网络关系图,通过STRING数据库、生物学信息注释数据库(DAVID)和KEGG Pathway数据库等进行蛋白互作关系分析、靶点基因功能富集分析和信号通路分析。结果筛选得到西瓜皮8个活性营养成分,通过Degree、Betweenness Centrality、Closeness Centrality等网络拓扑特征评价筛选出22个靶标在防治糖尿病过程中起重要的作用,并利用KEGG数据库对22个靶标进行相关通路富集分析,筛选出31条通路参与防治糖尿病作用。网络分析结果表明西瓜皮防治糖尿病的作用机制可能与Pathways in cancer、Proteoglycans in cancer、Chronic myeloid leukemia、Hepatitis B等信号通路过程有关,同时也与参与RNA聚合酶Ⅱ启动子对转录的正调控、信号转导、凋亡过程的负调控、昼夜节律、细胞缺氧反应、转录因子NF-kappaB活性的负调控等多种生物学过程的正负调控有关,从而达到增加组织对胰岛素的敏感性,改善代谢,减轻胰岛素抵抗,降低心血管并发症等作用发挥多成分、多靶点、多途径防治糖尿病的生物学效应。结论网络药理学为寻找西瓜皮营养成分防治糖尿病的分子作用机制奠定了基础,也为西瓜皮药用价值的深入研究及开发利用提供了理论依据。

Objective:To explore the potential molecular mechanism of watermelon peel nutrition in the treatment of diabetes mellitus(DM)by using the method of network pharmacology.Methods:Firstly,the active nutritional components of watermelon peel were screened by consulting related literatures(CNKI,PubMed)and databases such as TCMSP,PubChem,etc.,and taking pharmacological activity or ADME parameters as indexes.Through BATMAN-TCM database,traditional Chinese medicine target database,HIT and TTD database,the potential targets of watermelon peel nutrition in the treatment of diabetes were screened,the target data set was established,and the diabetes related targets were screened by OMIM database.The interaction target of watermelon peel and diabetes mellitus was constructed by using PPI database,the complex network diagram of"drug component-target-disease"was constructed by Cytoscape software,STRING database,(DAVID)database and KEGG Pathway database were used to analyze the protein interaction,target gene function enrichment and signal pathway.Results:Eight active nutritional components were selected from watermelon peel,and 22 targets were screened out by Degree,Betweenness Centrality,Closeness Centrality and other network topological characteristics,which played an important role in the treatment of diabetes mellitus.KEGG database was used to analyze 22 targets,and 31 pathways were selected to participate in the treatment of diabetes.The results of network analysis showed that the mechanism of watermelon peel in the treatment of diabetes might be related to the signal pathway of Pathways in cancer,Proteoglycans in cancer,Chronic myeloid leukemia,Hepatitis B,and the positive regulation of transcription by RNA polymeraseⅱpromoter.Signal transduction,negative regulation of apoptosis,circadian rhythm,anoxia response,negative regulation of transcription factor NF-kappaB activity and other biological processes.So as to increase tissue sensitivity to insulin,improve metabolism,reduce insulin resistance,reduce cardiovascular complications and other effects to play a multi-component,multi-target,multi-way biological effect of diabetes treatment.Conclusion:Network pharmacology laid a foundation for finding the molecular mechanism of the nutritional components of watermelon skin in the treatment of diabetes,and also provided a theoretical basis for the further study and development of the medicinal value of watermelon peel.