ABSTRACT
Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, affecting approximately 25% of the population with limited effective pharmacological treatments. According to recent research, phytochemicals from Vitis vinifera and Aframomum melegueta offer potential therapeutic benefits in the management of NAFLD. The application of computational screening proves to be a valuable strategy for the discovery of promising drug candidates. Objective: To perform computational screening of phytochemicals from Vitis vinifera (grapes) and Aframomum melegueta (alligator pepper) to identify potential candidates for treating nonalcoholic fatty liver disease (NAFLD). Methods: This study utilized computational approaches to analyze protein-ligand interactions for drug discovery. The structures of target proteins (PDB IDs: 5LX9, 1PKW, 1DQ9, and 6TSG) were retrieved from the Protein Data Bank (PDB) and prepared using Discovery Studio. Ligands from Vitis vinifera and Aframomum melegueta were obtained from PubChem, optimized, and converted into docking-compatible formats. Molecular docking was conducted using AutoDock Vina within PyRx, followed by pharmacophore modeling in Discovery Studio. ADMET properties were predicted using SwissADME, while toxicity assessments were performed via ProTox-3.0. 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 Vitis vinifera (e.g., Flavylium, Afzelchin, Cyanidin, Catechin, Riboflavin, and Alpha-tocopherol), showed high binding affinities particularly with 5LX9 and 1PKW. Similarly, compounds from Aframomum melegueta (e.g., Piperine, Quercetin, Beta-sitosterol, 6-paradol, 6-shogaol, and Catechins) exhibited promising interactions with 5LX9, 1PKW, and 6TSG. Conclusion: The study highlights the potential of Vitis vinifera and Aframomum melegueta as natural therapeutics for NAFLD. The strong binding affinities and favorable pharmacokinetic profiles of selected phytochemicals suggest their therapeutic viability. Further research is recommended to optimize their efficacy and safety through in-vitro and in-vivo studies, paving the way for plant-based drug discovery in NAFLD treatments.
