Neuroprotective Effects of Hippeastrum elegans Extract: Anticholinesterase Effect In Silico and In Vivo Studies in the Scopolamine-Induced Memory Deficits Model in Rat

Alzheimer’s disease is a chronic and progressive neurodegenerative disease that causes severe cognitive decline and memory loss. Alzheimer’s disease is the most prevalent cause of dementia in elderly people. Most medications currently available for the treatment of Alzheimer’s disease are acetylcholinesterase inhibitors. Amaryllidaceae plants, such as Hippeastrum elegans (Spreng.) H.E.Moore, are known to biosynthesize alkaloids, which exhibit acetylcholinesterase inhibitory activity. The aim of this study was to evaluate the effects of H. elegans extract bulbs and galantamine, on memory impairment caused by scopolamine administration in mice. Mice were treated orally for 7 days with H. elegans extract (25, 50, and 100 mg/kg) or galantamine (3 mg/kg); on the eighth day, scopolamine-induced memory deficits were evaluated. Scopolamine (3 mg/kg) was injected intraperitoneally 30 min before the Y-maze (working memory) and passive avoidance (aversive memory) tests. Acetylcholinesterase inhibition was evaluated in the hippocampal and cortex tissues of treated animals and the antioxidant activity of H. elegans was evaluated in vitro . Additionally, molecular docking was performed to investigate the probability of alkaloids to bind to the active site of the acetylcholinesterase. Scopolamine caused a significant deficit in working and aversive memory. Hippeastrum elegans also protected against working and aversive late memory impairment. The molecular docking study indicated a strong interaction of the alkaloids with the active site of acetylcholinesterase. These findings show that treatment with H. elegans protected against scopolamine-induced memory impairment in mice, probably by inhibiting acetylcholinesterase activity and exerting antioxidant action. Therefore, H. elegans can serve as an adjuvant treatment for Alzheimer’s disease. Graphical Abstract