Exploring the molecular mechanism of budesonide enteric capsules in the treatment of IgA nephropathy based on bioinformatics

IgA nephropathy (IgAN) is a prevalent primary glomerular disease and a major contributor to end-stage renal disease (ESRD). Budesonide Enteric Capsules (Nefecon®) are the first treatment approved by the U.S. Food and Drug Administration (FDA) targeting galactose-deficient IgA1 (Gd-IgA1) synthesis in the terminal ileum for IgAN. However, the detailed molecular mechanisms underlying its efficacy remain to be fully elucidated. In this study, we utilized bioinformatics approaches to integrate data from the GeneCards, CTD, and OMIM databases, identifying 787 IgAN-related targets. Additionally, we employed the PharmMapper, CTD and TargetNet databases to predict 384 budesonide targets, ultimately pinpointing 122 common targets. GO and KEGG enrichment analyses indicated that these targets are significantly enriched in biological processes such as apoptosis, inflammation responses, and cell proliferation, as well as in key pathways, including pathways in cancer, the PI3K-Akt signaling pathway, and the IL-17 signaling pathway. Protein-protein interaction (PPI) network analysis identified 10 core targets, including IL-6, TNF, AKT1, and TGF-β1, all of which exhibited strong binding affinity with budesonide in molecular docking studies. This study suggests that budesonide may exert its therapeutic effects on IgAN through multi-target and multi-pathway synergistic actions, offering valuable insights for its application in the clinical management of IgAN.