Network pharmacology and molecular docking to elucidate the potential mechanism of Fernandoa adenophylla against oxidative stress-mediated nephroprotection

Oxidative stress is a central pathomechanism in chronic kidney disease (CKD), yet the nephroprotective potential of Fernandoa adenophylla (Bignoniaceae), a medicinally important tree of South and Southeast Asia, remains mechanistically uncharacterised. This study employed an integrated network pharmacology and molecular docking strategy to systematically elucidate the multi-target mechanism of F. adenophylla against oxidative stress-mediated renal injury. Thirteen phytochemical constituents were retrieved from curated databases and subjected to ADME screening via SwissADME; eight compounds including lapachol, α-lapachone, adenophyllone, peshwaraquinone, ursolic acid, and oleanolic acid met Lipinski’s Rule-of-Five criteria and were retained. Protein targets for these compounds were predicted via SwissTargetPrediction and intersected with 287 oxidative stress nephroprotection disease targets retrieved from GeneCards, OMIM, DisGeNET, and TTD, yielding 53 shared candidate targets. A tripartite Compound–Target–Disease network constructed in Cytoscape identified AKT1, TP53, NFE2L2 (NRF2), KEAP1, CASP3, and MAPK1 as principal hub targets. STRING-based protein–protein interaction analysis and CytoHubba MCC ranking corroborated these hubs, while GO and KEGG enrichment mapped the target set to the PI3K/AKT, apoptosis, NF-κB, and HIF-1α signalling pathways. Molecular docking with AutoDock Vina revealed that adenophyllone exhibited the highest binding affinity for KEAP1 (−8.9 kcal/mol) and lapachol for AKT1 (−8.2 kcal/mol). These interactions were further validated by 100 ns GROMACS molecular dynamics simulations demonstrating stable RMSD profiles, sustained hydrogen-bond occupancy, and favourable MM-PBSA binding free energies. Collectively, these results indicate that F. adenophylla likely exerts nephroprotection through coordinated modulation of the KEAP1/NRF2 antioxidant axis, the AKT1/TP53/CASP3 survival–apoptosis axis, and the MAPK1/TNF inflammatory–oxidative crosstalk axis, providing a rational computational foundation for in-vitro and in-vivo experimental validation.