Ameliorative role of ellagic acid against acute liver steatosis in adult zebrafish experimental model

Non-alcoholic fatty liver disease (NAFLD), also known as hepatic steatosis, is highly prevalent in developed countries despite advancements in clinical modalities. Therefore, there is a need for identifying the bioactive molecular entity (BME) that can therapeutically intervene with liver steatosis progression. In this study, we investigated the efficacy of one such BME - ellagic acid (EA) to ascertain its molecular therapeutic potential against iodoacetamide (IAA) mediated liver steatosis in an adult zebrafish model. Dysregulation of lipid homeostasis by IAA and its amelioration by EA was examined by histological staining and biochemical analysis in the adult zebrafish model. Furthermore, the gene expression analysis of 3-hydroxy methyl glutaryl (HMG) CoA reductase, fatty acid synthase and sterol receptor binding protein-1c in IAA mediated liver steatosis and its regulation by EA was also studied by reverse transcription-polymerase chain reaction (RT-PCR). Concurrently, the drug likeliness and pharmacokinetic properties of EA in comparison to Simvastatin (SIM) were analysed computationally by absorption, distribution, metabolism, and excretion (ADME) analysis. Also, the atomic level interactions of HMG-CoA reductase binding pocket with EA in comparison to SIM were examined by the molecular docking approach to ascertain their comparative binding energy (ΔG) and binding pose. Molecular docking revealed prominent hotspot residues (Gly 765, Gln 766, Asp 767, Gly 808) key to both EA and SIM interaction. All the above results revealed that the experimental observations wherein good agreement with the computational analysis substantiating the promising therapeutic potential of EA against IAA mediated liver steatosis.