Study on the Mechanism of Budesonide in the Treatment of IgA Nephropathy Based on Network Pharmacology

Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis in China and worldwide, approximately 25%-30% of patients will progress to end-stage renal disease within 20 years after diagnosis. Currently, there is no effective and safe treatment specifically for IgAN. In recent years, there has been a rapid progress in the research of new drugs for IgAN, among which the targeted delayed-release budesonide capsules is the first allopathic drug for IgAN globally. Objective To investigate the mechanism of corticosteroid budesonide capsules in the treatment of IgAN based on network pharmacology. Methods Chemical Book platform was used to screen the targets of budesonide; GeneCards and CTD databases were utilized to obtain the relevant targets of IgAN. The intersection of budesonide targets and IgAN targets was obtained through a Venn diagram. A protein-protein interaction (PPI) network map was constructed, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting targets. Results A total of 242 targets for budesonide, 1 443 candidate targets for IgAN, and 146 intersecting targets were selected. The 15 core targets in the PPI network included interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-10 (IL-10), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), interleukin-1B (IL-1B), interleukin-4 (IL-4), interleukin-8 (CXCL8), gene on chromosome 1 (JUN), interleukin-13 (IL-13), interleukin-2 (IL-2), chemokine 2 (CCL2), toll-like receptor 4 (TLR4), colony-stimulating factors (CSF2), and albumin (ALB). Enrichment analysis revealed 1 646 GO enrichment results and 174 KEGG signaling pathways. The biological processes (BP) mainly involved positive regulation of phosphorylation, inflammatory response, and positive regulation of cell movement. The cellular components (CC) mainly involved cytoplasmic vesicle lumen, cyst cavity, and secretory granule lumen. The molecular functions (MF) mainly involved receptor signaling activity, receptor regulator activity, and receptor ligand activity. The KEGG signaling pathways mainly included interleukin 17 signaling pathway, cytokine-cytokine receptor interaction, pathways in cancer, and tumor necrosis factor signaling pathway. Conclusion This study provides preliminary verified that budesonide can treat IgAN by targeting IL-6, TNF, IL-10, VEGFA, EGFR, and other targets, through multiple signaling pathways, like cytokine-cytokine receptor interaction, interleukin-17 signaling pathway, pathways in cancer, and tumor necrosis factor signaling pathway, providing a theoretical basis for further research and clinical practice of budesonide.