All the in-silico (Protein ID: 5BTR) and in-vivo (high-fat diet + CCl4 induced NAFLD/NASH in CF-1 mice) experiments were carried out using eight synthesized cinnamyl sulfonamide hydroxamate derivatives to identify their inhibitory action against NOTCH-1 receptors by activation of SIRT-1 and disease prevention activity in NAFLD/NASH animal model (Fig. 1). This evidence concerns the gene NOTCH1 and metabolic dysfunction-associated steatohepatitis.