Network Pharmacology and Molecular Docking-Based Investigation of Empagliflozin's Therapeutic Potential in Chronic Kidney Disease
Abstract
Chronic kidney disease (CKD) is a progressive global health challenge. While empagliflozin, a selective SGLT2 inhibitor, is known to attenuate CKD progression through mechanisms beyond glycemic control, the precise molecular pathways remain incompletely characterized and warrant further investigation. This study employed an integrated network pharmacology and molecular docking approach to elucidate the multi-target mechanisms of empagliflozin in CKD. Initial evaluation demonstrated that empagliflozin exhibits favorable physicochemical properties, drug-likeness, and ADMET profiles, supporting its potential as an effective orally administered therapeutic option for CKD management. Network analysis identified 221 shared molecular targets between empagliflozin and CKD-associated genes. Topological analysis of the protein-protein interaction (PPI) network revealed ten critical hub proteins-GAPDH, IL6, EGFR, HSP90AA1, NFKB1, HSP90AB1, MTOR, MAPK3, IL2, and PIK3CA-which serve as key regulators in CKD pathophysiology. Gene Ontology and KEGG pathway enrichment analyses indicated that these shared targets are significantly involved in phosphorylation, signal transduction, and central signaling cascades associated with CKD progression, including the PI3K-Akt, FoxO, HIF-1, and AGE-RAGE pathways. Molecular docking simulations corroborated empagliflozin's multi-target affinity, demonstrating particularly strong binding energies toward HSP90AB1 (-10.85 kcal/mol), MAPK3 (-9.46 kcal/mol),…
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