Abstract
Abstract
Diabetic nephropathy (DN) ranks as the primary contributor to end-stage renal disease across the globe, characterized by progressive glomerular mesangial proliferation and tubular interstitial fibrosis, which poses a severe threat to public health. Pinocembrin is a major flavonoid compound that has been reported to exhibit a variety of prominent biological effects. However, its dual regulatory effects on glomerular and tubular injuries in DN remain unclear. The present study aims to investigate the potential role of pinocembrin in alleviating the progression of DN, providing a combination therapeutic strategy. In
vivo
experiments were performed to verify its efficacy in improving renal injury and fibrosis of pinocembrin in Lep
db
/Lep
db
(
db/db)
mice. Pinocembrin-related targets were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP), Comparative Toxigenomics Database (CTD), Swiss Target Prediction, and Symmap databases. Differentially expressed genes in DN tubules and glomeruli were obtained from Gene Expression Omnibus (GEO) dataset GSE30122. Overlapping targets between pinocembrin and DN tissues were identified, followed by Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking predicted potential binding interactions between pinocembrin and key targets. In
vitro
experiments demonstrated that in HG-induced HK-2 cells, pinocembrin might target HSP90AB1 to suppress inflammatory response and epithelial-mesenchymal transition, thereby alleviating tubular fibrosis injury. In HG-treated SV40 cells, pinocembrin downregulated expression of VEGFR, thereby inhibiting cell proliferation and extracellular matrix deposition to improve glomerular pathological damage. This study clarifies the dual protective mechanism of pinocembrin on DN
via
regulatory pathways. These findings provide experimental foundation and theoretical insight for the application of pinocembrin as a functional food ingredient for the prevention and treatment of DN.