Molecular docking, dynamics simulations, and in vivo studies of gallic acid in adenine-induced chronic kidney disease: targeting KIM-1 and NGAL

Abstract

Gallic acid (GA), a naturally occurring compound with antioxidant, anti-inflammatory, anti-apoptotic, and regenerative properties, has gained attention for its potential protective role against kidney dysfunction and diseases, though its therapeutic efficacy in this context remains underexplored. The primary objective of this study was to explore the therapeutic effects of GA in treating adenine-induced chronic kidney disease (CKD) in male Wistar rats. The study evaluated GA’s therapeutic potential against CKD, along with its pharmacokinetic and drug-likeness properties through a comprehensive analysis. It also assessed GA’s inhibitory effects on key kidney proteins, KIM-1 and NGAL, using gene expression analysis, molecular docking, and molecular dynamics simulations. The results demonstrated a range of positive effects, including significant improvement in adenine-induced kidney damage, as shown by changes in urine and serum markers, as well as oxidative stress biomarkers, following GA treatment. The study revealed that GA effectively suppresses the adenine-induced gene expression of KIM-1 and NGAL. Furthermore, GA adhered to Lipinski’s Rule of Five, and molecular docking analysis indicated strong interactions and low binding energies between GA and the target proteins KIM-1 and NGAL, further supporting its efficacy in targeting these markers. Additionally, 100 ns molecular dynamics simulations showed that gallic acid has a stronger binding affinity for NGAL than for KIM-1, with higher binding energy, stability, and stronger hydrogen bonds, suggesting that it primarily influences NGAL interactions. This study underscores gallic acid’s potential in reducing adenine-induced kidney damage and improving kidney function, with computational evidence supporting its promise as a treatment for CKD.