Abstract
Background
Tripterygium wilfordii has been widely used for idiopathic membranous nephropathy (IMN), while the pharmacological mechanisms are still unclear. This study is aimed at revealing potential therapeutic targets and pharmacological mechanism of tripterygium wilfordii for the treatment of IMN based on network pharmacology.
Methods
Active components of tripterygium wilfordii were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. IMN-associated target genes were collected from GeneCards database, DisGeNET database, and OMIMI database. VENNY 2.1 was used to identify the overlapping genes between active compounds of tripterygium wilfordii and IMN target genes. Using STRING database and Cytoscape 3.7.2 software to analyze interactions among overlapping genes. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the targets were analyzed using the Rx64 4.0.2 software, colorspace, stringi, DOSE, clusterProfiler, and enrichplot packages.
Results
A total of 153 compounds-related genes, 1485 IMN-related genes were obtained, and 77 overlapping genes between them were identified. The protein–protein interactions network indicated that the targets AKT1, TNF, VEGFA, TP53, PTGS2, CXCL8, MAPK8, STAT3, JUN, and CASP3 play an important role in the treatment effect of tripterygium wilfordii for IMN. The enrichment analysis showed that the main pathways of targets were AGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway.
Conclusion
This study reveals potential mechanisms of multi-component and multi-target of tripterygium wilfordii for the treatment of IMN based on network pharmacologic approach, and provide a scientific basis for further experimental studies.