Mulelu_2026_Chem.Biodivers_23_e71409

Alzheimer's disease (AD) is a disease associated with loss of brain cholinergic functions and a common cause of dementia. Diabetes and inflammation have been linked to some pathways contributing to AD pathogenesis. In this study, the effects of Withania somnifera (W. somnifera) root ethanol extract (WSEE) on lipoxygenase, butyrylcholinesterase (BChE), protein denaturation, and carbohydrate digestive enzymes were determined using in vitro and in silico experimental models. WSEE cytotoxicity on neuroblastoma cell lines (SH-SY5Y) and the molecular docking simulation of its compounds were also investigated. WSEE analysis showed the presence of terpenoids, flavonoids, alkaloids, and tannins. The extract showed significant (p < 0.05) inhibition of protein denaturation (IC(50) = 558.6 microg/mL), lipoxygenase (IC(50) = 175.6 microg/mL) and BChE (IC(50) = 313.6 microg/mL) than ibuprofen (IC(50) = 191.1 microg/mL), vitamin C (IC(50) = 44.97 microg/mL), and rivastigmine (IC(50) = 123.7 microg/mL), respectively. It also inhibited alpha-glucosidase (IC(50) = 343.0 microg/mL) and reduced SH-SY5Y cell viability at <= 80 microg/mL. The docking studies revealed that sitoindoside IX, somniferin, withanolide B, and withasomniferolide B in the plant exhibit high binding affinities, where withasomniferolide B presents the highest docking scores (-11.4 kcal/mol) with alpha-amylase. Further in vivo and molecular studies are needed to validate the plant's usefulness in AD management.