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

BACKGROUND: Although thunder god vine (Tripterygium wilfordii) 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 T. wilfordii for the treatment of IMN based on network pharmacology. METHODS: Active components of T. wilfordii 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 T. wilfordii 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 T. wilfordii 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 T. wilfordii for the treatment of IMN based on network pharmacological, and provided a scientific basis for further experimental studies.