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基于网络药理学的治疗特发性膜性肾病的作用机制

Mechanism of action of for treatment of idiopathic membranous nephropathy based on network pharmacology.

作者信息

Shi Honghong, Hou Yanjuan, Su Xiaole, Qiao Jun, Wang Qian, Guo Xiaojiao, Gao Zhihong, Wang Lihua

机构信息

Division of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Division of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Ren Fail. 2022 Dec;44(1):116-125. doi: 10.1080/0886022X.2021.2024850.

Abstract

BACKGROUND

Although thunder god vine () has been widely used for treatment of idiopathic membranous nephropathy (IMN), the pharmacological mechanisms underlying its effects are still unclear. This study investigated potential therapeutic targets and the pharmacological mechanism of for the treatment of IMN based on network pharmacology.

METHODS

Active components of were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. IMN-associated target genes were collected from the GeneCards, DisGeNET, and OMIM databases. VENNY 2.1 was used to identify the overlapping genes between active compounds of and IMN target genes. The STRING database and Cytoscape 3.7.2 software were used to analyze interactions among overlapping genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the targets were performed using Rx64 4.0.2 software, colorspace, stringi, DOSE, clusterProfiler, and enrichplot packages.

RESULTS

A total of 153 compound-related genes and 1485 IMN-related genes were obtained, and 45 core genes that overlapped between both categories were identified. The protein-protein interaction network and MCODE results indicated that the targets TP53, MAPK8, MAPK14, STAT3, IFNG, ICAM1, IL4, TGFB1, PPARG, and MMP1 play important roles in the treatment of on IMN. Enrichment analysis showed that the main pathways of targets were the AGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway.

CONCLUSION

This study revealed potential multi-component and multi-target mechanisms of for the treatment of IMN based on network pharmacological, and provided a scientific basis for further experimental studies.

摘要

背景

雷公藤已被广泛用于治疗特发性膜性肾病(IMN),但其作用的药理机制仍不清楚。本研究基于网络药理学探讨雷公藤治疗IMN的潜在治疗靶点和药理机制。

方法

从中药系统药理学数据库和分析平台获取雷公藤的活性成分。从GeneCards、DisGeNET和OMIM数据库收集IMN相关的靶基因。使用VENNY 2.1软件确定雷公藤活性成分与IMN靶基因之间的重叠基因。利用STRING数据库和Cytoscape 3.7.2软件分析重叠基因之间的相互作用。使用Rx64 4.0.2软件、colorspace、stringi、DOSE、clusterProfiler和enrichplot软件包对靶标进行基因本体论和京都基因与基因组百科全书通路富集分析。

结果

共获得153个化合物相关基因和1485个IMN相关基因,确定了两类基因之间重叠的45个核心基因。蛋白质-蛋白质相互作用网络和MCODE结果表明,TP53、MAPK8、MAPK14、STAT3、IFNG、ICAM1、IL4、TGFB1、PPARG和MMP1等靶点在雷公藤治疗IMN中起重要作用。富集分析表明,靶点的主要通路为AGE信号通路、IL-17信号通路、TNF信号通路和Toll样受体信号通路。

结论

本研究基于网络药理学揭示了雷公藤治疗IMMIM多成分、多靶点机制,为进一步的实验研究提供了科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2cf/8856020/deaa9fea3863/IRNF_A_2024850_F0001_C.jpg

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