Diabetic kidney disease (DKD) is a major contributor to chronic kidney failure and is closely associated with inflammatory pathways, particularly those involving TNF-α and NF-κB. In this study, phytocompounds from Pedalium murex were computationally assessed for their potential therapeutic roles in DKD using a multi-step in silico pipeline. 29 phytochemicals were initially retrieved from the IMPPAT database, and eight were shortlisted based on ADME and toxicity profiling. Target prediction using SwissTargetPrediction and STITCH identified 267 compound-associated genes with 160 overlapping DKD-related genes obtained from the GeneCards and OMIM databases (n = 4904). Protein-protein interaction (PPI) analysis using STRING and Cytoscape revealed NF-κB and TNF-α as key hub genes, which were further validated through functional enrichment and KEGG pathway analysis, highlighting the AGE-RAGE signalling pathway in diabetic complications. Structural validation using QMEANDisCo, Ramachandran plots, and ProSA confirmed the reliability of the protein target. Molecular docking predicted energetically favourable binding confirmations of Episesamin (-5.52 kcal/mol for TNF-α and -6.5 kcal/mol for NF-κB) and Sesamolin (-5.75 kcal/mol for TNF-α and -6.99 kcal/mol for NF-κB) compared to the control drug, Dapagliflozin (-5.39 kcal/mol for TNF-α and -5.16 kcal/mol for NF-κB). MDS over 200 ns demonstrated stable interactions of the ligands with the protein targets through RMSD, RMSF, Rg, SASA, H-bond, PCA, FEL, and MM-PBSA analyses. Sesamolin exhibited superior binding to NF-κB, whereas Episesamin showed a stronger affinity for TNF-α. These findings suggest that P. murex-derived compounds, particularly Episesamin and Sesamolin, emerge as computationally prioritized candidates for further experimental validation in DKD-associated inflammatory pathways.
Das et al. (Wed,) studied this question.