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基于罗汉果治疗糖尿病肾病机制的网络药理学和分子对接分析
于洋,田丹,倪东贺,张铎
PDF(1122 KB)
PDF(1122 KB)
基于罗汉果治疗糖尿病肾病机制的网络药理学和分子对接分析
Network pharmacologry and molecular docking analysis based on mechanism of monk fruit in treatment of diabetic nephropathy
目的 利用网络药理学分析罗汉果对糖尿病肾病(DN)的改善作用,阐明其可能的相关机制。 方法 采用中药系统药理学数据库和分析平台(TCMSP)确定罗汉果中的有效成分及其作用靶点。通过DisGeNET数据库和GeneCards数据库筛选DN靶基因。将罗汉果与DN靶点进行对比,获取罗汉果对DN的关键靶点。通过STRING 数据库和 Cytoscape 软件构建蛋白-蛋白互作(PPI)网络图,通过Cytoscape 软件进行基因本体论(GO) 功能富集分析和京都基因与基因组百科全书 (KEGG) 信号通路富集分析。采用分子对接技术预测DN核心靶点与罗汉果主要活性成分的结合能力。 结果 采用TCMSP 数据库结合选入标准共筛选出罗汉果5种活性成分(ZINC03860434、Perlolyrine、beta-sitosterol、Kaempferol和Flazin)及丝氨酸/苏氨酸蛋白激酶1(AKT1)、转录因子RELA、c-Jun氨基末端激酶(JUN)和肿瘤坏死因子(TNF)为代表的85个靶点,其中kaempferol所含靶点最多。筛选出的85个靶点中与DN相关的靶点有34个。GO功能富集分析主要涉及氧化应激、炎症及凋亡调控和细胞信号传导等生物学过程(BP)。KEGG信号通路富集分析涉及晚期糖基化终产物(AGE)-AGE受体(AGE-RAGE)信号通路、TNF信号通路和C型凝集素受体信号通路等。罗汉果主要活性成分与DN靶点蛋白分子对接分析,5种活性成分分子对接结合能均在-8.00~ -5.00 kJ·mol-1之间。 结论 Kaempferol是罗汉果中对DN治疗最有效的活性成分,其作用机制主要与抑制炎症有关。
Objective To analyze the improvement effect of monk fruit on diabetic nephropathy(DN) by network pharmacology,and to elucidate its possible related mechanism. Methods The Traditional Chinese Medicine Systems Pharmacology(TCMSP) Database was used to detect the active ingredients and their targets of monk fruit; the DN target genes were screened out by DisGeNET Database and Genecards Database; the key targets of monk fruit against DN were obtained by comparing the monk fruit with DN targets; protein-protein interaction (PPI) network diagram was constructed by STRING Database and Cytoscape software; Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed by Cytoscape software.Molecular docking technology was used to predict the binding abilities of the core targets and the main active ingredients of monk fruit. Results The TCMSP Database combined with the selection criteria was used to screen out a total of five active ingredients of monk fruit (ZINC03860434, Perlolyrine, beta-sitosterol, Kaempferol, and Flazin) as well as 85 targets represented by serine/threonine protein kinase 1 (AKT1),transcription factor RELA, c-Jun N-terminal kinase (JUN),and tumor necrosis factor (TNF). Among them, Kaempferol contained the most targets.Among the 85 targets, 34 were associated with DN.The GO functional enrichment analysis mainly included biological process(BP) such as oxidative stress, regulation of inflammation and apoptosis, and cell signaling transduction.The KEGG enrichment analysis included advanced glycosylation end product(AGE)-receptor of AGE (AGE-RAGE) signaling pathway, TNF signaling pathway, and C-type lectin receptor signaling pathway.The results molecular docking technology of the main active ingredients of monk fruit and DN target proteins showed that 5 kinds of molecular docking engergy were -8.00--5.00 kJ·mol-1. Conclusion Kaempferol is the most effective active ingredient in the monk fruit for the treatment of DN, and its mechanism is mainly related to anti-inflammatory.
罗汉果 / 糖尿病肾病 / 网络药理学 / 炎症因子 / 蛋白-蛋白互作网络
Monk fruit / Diabetic nephropathy / Network pharmacology / Inflammation factor / Protein-protein interaction
R285.5
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