Redox Modulation in Down Syndrome by Platanus orientalis -derived Compounds Targeting the SOD1–GPx Axis

Down syndrome (DS), caused by trisomy 21, is characterized by chronic oxidative stress resulting from overexpression of the superoxide dismutase 1 (SOD1) gene without a proportional increase in downstream antioxidant enzymes such as glutathione peroxidase (GPx). This imbalance leads to hydrogen peroxide accumulation, contributing to neurodegeneration and systemic complications. Plant-derived phytochemicals with antioxidant properties may offer a multi-target strategy to restore redox homeostasis in DS. The present study aimed to evaluate phytochemicals derived from Platanus orientalis for their potential to modulate oxidative stress in Down syndrome by targeting the SOD1–GPx redox axis using in-silico molecular docking and pharmacokinetic analysis. Seven phytochemicals were selected from the IMPPAT database based on reported antioxidant activity. The three-dimensional structures of SOD1 (PDB ID: 2C9V) and GPx (PDB ID: 2R37) were retrieved from the Protein Data Bank and prepared for docking. Molecular docking was performed to assess binding affinities and interaction profiles. Drug-likeness, pharmacokinetic parameters, and blood–brain barrier permeability were evaluated using in-silico ADMET prediction tools. All selected phytochemicals exhibited favorable binding interactions with both SOD1 and GPx, with binding energies ranging from −5.0 to −7.5 kcal/mol for SOD1 and −4.8 to −6.7 kcal/mol for GPx. Tiliroside demonstrated the strongest affinity towards SOD1, while kaempferol and betulinic acid showed stable and consistent interactions with both targets. Five compounds—platanin, kaempferol, caffeic acid, allantoin, and betulinic acid—displayed acceptable drug-likeness profiles, although none were predicted to cross the blood–brain barrier. Platanus orientalis–derived phytochemicals demonstrate promising dual-target interactions with SOD1 and GPx, supporting their potential role in modulating oxidative stress in Down syndrome. These findings warrant further experimental validation to explore their therapeutic relevance and translational potential.