Nephrolithiasis is a widespread chronic condition that can significantly impair kidney function and elevate the risk of chronic kidney disease and end-stage renal disease. The complex and poorly understood pathogenesis of nephrolithiasis has limited the development of effective preventive and therapeutic strategies, thus highlighting the urgent need for novel and safe treatments.

To explore potential therapeutic targets and mechanisms for nephrolithiasis, we identified nephrolithiasis-related targets using multiple disease databases. We then performed biological functional enrichment analysis to elucidate the key pathways involved. Protein-protein interaction (PPI) networks were constructed, and hub targets were identified through Cytoscape and MCODE analysis. Potential anti-nephrolithiasis compounds were screened using molecular docking and molecular dynamics simulations, with the most promising candidates further validated through in vivo and in vitro experiments.

Network pharmacology analysis identified 223 targets associated with kidney stones and LUT (Luteolin). KEGG database enrichment analysis highlighted the involvement of several Our comprehensive analysis identified 623 targets associated with nephrolithiasis. KEGG pathway enrichment analysis revealed significant links to metabolic pathways and key signaling cascades, including the PI3K-Akt, MAPK, and Rap1 pathways. Through Cytoscape analysis, we pinpointed a critical hub target implicated in nephrolithiasis. Molecular docking and dynamics simulations showed that epicatechin has a strong binding affinity for IL-1α. Subsequent in vitro and in vivo experiments further confirmed that epicatechin effectively mitigates nephrolithiasis by modulating the IL-1α/NF-κB signaling pathway.

This study provides comprehensive evidence for the anti-nephrolithiasis effects of epicatechin, supported by both network pharmacology and experimental validation. The protective mechanism of epicatechin involves modulation of the IL-1α/NF-κB signaling pathway. These findings offer valuable insights for the development of novel therapeutic strategies against nephrolithiasis.