An in silico studies of Solanum erianthum compounds as PPAR-α and TGF-βR1 modulators in oxidative stress-induced liver injury

Oxidative stress–induced liver injury is a major pathological condition characterized by excessive reactive oxygen species and disruption of antioxidant defense mechanisms. Identifying natural compounds with the ability to modulate key signaling proteins offers a potential therapeutic strategy. In this study, ADME screening, molecular docking, and molecular dynamics (MD) simulations were employed to evaluate the binding interactions of phytoconstituents of Solanum erianthum against two protein targets, PPAR-α (5HYK) and TGF-βR1 (3TZM), associated with oxidative stress liver injury. ADME screening of the phytoconstituents including caffeic acid, ferulic acid, tannic acid, rutin, p-coumaric acid, apigenin, saponin, naringin and quercetin reveals relatively druggable characteristics with tolerable oral bioavailability. Molecular docking analysis reveals favorable binding orientations within the active sites of 5HYK and 3TZM, respectively. The docking score ranges from -6.2 to -9.4 kcal/mol for 5HYK and -6.2 to -10.4 kcal/mol for 3TZM. All phytoconstituents engaged important residues through hydrogen bonding, hydrophobic interactions, and π–π stacking, suggesting potential activation and inhibitory activities. To further assess stability, MD simulations with the best docked complexes, 5HYK–Apigenin and 3TZM-Rutin show that the 5HYK–Apigenin complex possesses superior stability with low RMSD, compact packing, and stable H-bonds, whereas the 3TZM–Rutin complex showed moderate stability with higher flexibility and solvent exposure. MM/GBSA calculations yielded binding free energies of -12.87 kcal/mol for 5HYK-Apigenin and -22.13 kcal/mol for 3TZM-Rutin, confirming favorable binding for both complexes. Overall, the results indicate that phytoconstituents of S. erianthum , display a favorable binding interaction and stability, supporting its potential as a therapeutic agent against oxidative stress–induced liver injury.