Utilizing computational approaches for the prediction of alpha-PPAR inhibitors from baobab (Adansonia digitata) against non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), a silent killer, lacks a specific treatment because there is currently no medication approved by the Federal Drug Administration (FDA) for its treatment. So, this serious situation requires the use of all resources to remedy this problem. Reducing triglyceridemia may be a promising strategy to lower the risk of NAFLD. So, the aim of the present study was to predict a new potential alpha-PPAR agonist as a drug for NAFLD from baobab fruit (Adansonia digitata) using molecular docking. Compounds from baobab fruit using the PubChem database were selected. Filtration of compounds was carried out using the Lipinski rules and ADME parameters. Then, Molecular Operating Environment (MOE) software was used to prepare these compounds as ligands for docking simulations. The 3D structure of the PPAR-alpha receptor was retrieved from the Protein Data Bank (PDB) database for docking simulations. The analysis of Adansonia digitata fruit showed the presence of 102 compounds using PubChem database. When filtering these compounds using the Lipinski rule, only 23 compounds were recorded with 0 violations. After docking through MOE software, one compound, namely the carbohydrate, D-Glucitol, 1, 3:2, 4-bis-O-((4-ethylphenyl) methylene) gave the least negative score of energy complex (about −8.2333 Kcal/mol) while the reference Pioglitazone drug gave a score of −7.7763 Kcal/mol. RMSD for the carbohydrate compound was 1.4141, while in the reference drug, it was 1.9589. The amino acid (THR) in the carbohydrate, D-Glucitol, is hydrophilic and neutrally charged at a physiological pH, suggesting better absorption, while in the reference drug, the amino acid (HIS) is hydrophobic at a physiological pH, potentially limiting the drug’s absorption. Additionally, the ADME properties of the carbohydrate showed good pharmacokinetic properties. The D-Glucitol, 1,3:2,4-bis-O-((4-ethylphenyl)methylene) compound, isolated from baobab fruit, shows promising potential as a novel agonist for the PPAR-alpha receptor responsible for non-alcoholic fatty liver disease (NAFLD). Further in vivo studies are necessary to investigate this compound’s therapeutic efficacy.