基于网络药理学的方法揭示雷公藤红素抗糖尿病肾病的作用机制。
A Network Pharmacology-Based Strategy for Unveiling the Mechanisms of Tripterygium Wilfordii Hook F against Diabetic Kidney Disease.
机构信息
Department of Nephrology, Guang'anmen Hospital of China Academy of Traditional Chinese Medical Sciences, Beijing 100053, China.
Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
出版信息
J Diabetes Res. 2020 Nov 20;2020:2421631. doi: 10.1155/2020/2421631. eCollection 2020.
BACKGROUND
Diabetic kidney disease (DKD) poses a major public-health burden globally. Tripterygium wilfordii Hook F (TwHF) is a widely employed herbal medicine in decreasing albuminuria among diabetic patients. However, a holistic network pharmacology strategy to investigate the active components and therapeutic mechanism underlying DKD is still unavailable.
METHODS
We collected TwHF ingredients and their targets by traditional Chinese Medicine databases (TCMSP). Then, we obtained DKD targets from GeneCards and OMIM and collected and analyzed TwHF-DKD common targets using the STRING database. Protein-protein interaction (PPI) network was established by Cytoscape and analyzed by MCODE plugin to get clusters. In addition, the cytoHubba software was used to identify hub genes. Finally, all the targets of clusters were subjected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses via DAVID.
RESULTS
A total of 51 active ingredients in TwHF were identified and hit by 88 potential targets related to DKD. Compounds correspond to more targets include kaempferol, beta-sitosterol, stigmasterol, and Triptoditerpenic acid B, which appeared to be high-potential compounds. Genes with higher degree including VEGFA, PTGS2, JUN, MAPK8, and HSP90AA1 are hub genes of TwHF against DKD, which are involved in inflammation, insulin resistance, and lipid homeostasis. Kaempferol and VEGFA were represented as the uppermost active ingredient and core gene of TwHF in treating DKD, respectively. DAVID results indicated that TwHF may play a role in treating DKD through AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, insulin resistance, and calcium signaling pathway ( < 0.05).
CONCLUSION
Kaempferol and VEGFA were represented as the uppermost active ingredient and core gene of TwHF in treating DKD, respectively. The key mechanisms of TwHF against DKD might be involved in the reduction of renal inflammation by downregulating VEGFA.
背景
糖尿病肾病（DKD）在全球范围内造成了重大的公共卫生负担。雷公藤是一种广泛应用于降低糖尿病患者蛋白尿的草药。然而，对于 DKD 而言，一种整体网络药理学策略来研究其活性成分和治疗机制仍然不存在。
方法
我们通过中药数据库（TCMSP）收集雷公藤的成分及其靶点。然后，我们从 GeneCards 和 OMIM 中获得 DKD 靶点，并使用 STRING 数据库收集和分析雷公藤-DKD 常见靶点。通过 Cytoscape 构建蛋白质-蛋白质相互作用（PPI）网络，并使用 MCODE 插件进行分析以获取聚类。此外，使用 cytoHubba 软件识别枢纽基因。最后，通过 DAVID 对聚类的所有靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。
结果
共鉴定出 51 种雷公藤的活性成分，这些成分与 88 个与 DKD 相关的潜在靶点相吻合。化合物对应更多靶点的包括山奈酚、β-谷甾醇、豆甾醇和雷公藤三萜酸 B，这些化合物似乎是具有高潜力的化合物。具有更高程度的基因包括 VEGFA、PTGS2、JUN、MAPK8 和 HSP90AA1，是雷公藤治疗 DKD 的枢纽基因，它们涉及炎症、胰岛素抵抗和脂质稳态。山奈酚和 VEGFA 分别代表了雷公藤治疗 DKD 的最主要活性成分和核心基因。DAVID 结果表明，雷公藤可能通过 AGE-RAGE 信号通路、IL-17 信号通路、TNF 信号通路、胰岛素抵抗和钙信号通路（<0.05）发挥治疗 DKD 的作用。
结论
山奈酚和 VEGFA 分别代表了雷公藤治疗 DKD 的最主要活性成分和核心基因。雷公藤治疗 DKD 的关键机制可能涉及通过下调 VEGFA 减轻肾脏炎症。
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