Pakistan Journal of Pharmaceutical Sciences

Abstract: This study aims to investigate the neuroprotective effects of Utilito, a novel chalcone derivative isolated from Arisaema utile in a sodium azide-induced Alzheimer’s disease (AD) rat model. Anti-alzheimer activities were assessed through in silico molecular docking, simulation studies and in vivo studies. Utilito at doses of 100, 200, 300 mg/kg was administered in Wistar rats (n=6/group) for 14 days. Cognitive performance and locomotion were assessed through behavioural tests (Morris water maze, Y-maze, and open field). Biochemical assays measured the levels of oxidative stress biomarker including catalase (CAT) superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA). Molecular docking studies revealed a strong binding affinity of Utilito with monoamine oxidase (MAO-B), with a docking score of -41.4 kJ/mol. Conventional hydrogen bond interactions were observed between the MAO-B residues LEU171, TYR398, and TYR435 and the phenol ring of Utilito. Utilito also showed 71 ± 0.11% anti-oxidant activity in the DPPH assay. Behavioural tests utilizing animal models demonstrate the cognitive-enhancing effects of Utilito. Biochemical evaluations underscore the antioxidant properties of Utilito, offering valuable insights into their mechanisms of action at the cellular level. Utilito exhibits antioxidant activity and cognitive improvement in a rat AD model, suggesting its promise as a therapeutic candidate for AD.