ABSTRACT Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with limited effective pharmacological treatments. Recent studies suggest that Ocimum gratissimum and Curcuma longa contain bioactive phytochemicals with reported hepatoprotective properties, potentially offering therapeutic benefits. Computational screening serves as a cost effective approach to identifying promising drug candidates. Objective: To perform computational screening of phytochemicals from Curcuma longa (turmeric) and Ocimum gratissimum (scent leaf) to identify potential candidates for treating non-alcoholic fatty liver disease (NAFLD). Methods: This study employed computational techniques to analyze protein-ligand interactions for drug discovery. Target protein structures (PDB IDs: 5lx9, 1pkw, 1dq9, and 6tsg) were retrieved from the Protein Data Bank (PDB) and processed using Discovery Studio. Ligands from Ocimum gratissimum and Curcuma longa were obtained from PubChem, optimized, and converted into docking-compatible formats. AutoDock Vina facilitated molecular docking within PyRx, followed by pharmacophore modeling using Discovery Studio. ADMET properties were predicted via SwissADME, while ProTox-3.0 assessed ligand toxicity. Results: Molecular docking analysis revealed that several phytochemicals exhibited stronger binding affinities than standard drugs (metformin, pioglitazone, and rosuvastatin), suggesting their potential as therapeutic alternatives. Notably, ligands from Ocimum gratissimum (e.g., β sitosterol, apigenin, chrysin, luteolin, oleanolic acid, procyanidins, quercetin, rosmarinic acid, and rutin) showed high binding affinities, particularly with 1PKW and 1DQ9. Similarly, compounds from Curcuma longa (e.g., cinnamyl cinnamate, demethoxycurcumin, germacrone, turmeronol, and humuladienone) exhibited promising interactions with 5LX9, 1PKW, and 6TSG. Conclusion: Ligands from Ocimum gratissimum showed strong interactions with 1PKW and 1DQ9, while those from Curcuma longa exhibited promising binding with 5LX9 and 6TSG. Key phytochemicals, including Beta-Sitosterol, Apigenin, Chrysin, Luteolin, Oleanolic acid, Procyanidins, Quercetin, Rosmarinic acid, and Rutin, demonstrated significant interactions. ADMET analysis confirmed favourable pharmacokinetics, though toxicity profiling indicated potential risks. Further optimization and validation through in vitro and in vivo studies are recommended to enhance safety and therapeutic efficacy, positioning these phytochemicals as potential NAFLD treatments. xiii
