Oleo-Gum-Resin of Ferula persica: Phytochemical Analysis and Enzyme Inhibitory Activity Related to Alzheimer’s Disease

Background and objectives: Medicinal plants have effectively treated Alzheimer’s disease (AD). In this study, the oleo-gum-resin of Ferula persica known as sagapenum was selected to investigate its inhibitory activity toward enzymes involved in the creation and progression of AD. Also, the phytochemical analysis, which was not previously reported in the literature, was conducted. Methods: The in vitro inhibitory activity of dichloromethane, methanol, and aqueous extracts was investigated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) according to the modified Ellman’s method. Moreover, the phytochemical analysis of the most potent extract was conducted using different column chromatography techniques. Results: The dichloromethane extract showed selective BuChE inhibitory activity (IC50 = 23.41 µg/mL), compared with donepezil as the reference drug (IC50 = 1.97 µg/mL). Phytochemical analysis of the related extract led to the isolation and identification of aurapten, farnesiferol A, umbelliprenin, farnesiferol C, farnesiferone A, karatavicinol, ferocaulidin, and ligupersin A, which were assayed toward cholinesterases (ChEs). Farnesiferol A was the most potent and selective inhibitor of BuChE (IC50 = 31.46 µg/mL). Moreover, it showed good β-secretase 1 (BACE1) inhibitory activity (IC50 = 5.14 µM), compared with the positive control, OM99-2 (IC50 = 0.014 µM) to be considered a multi-target directed ligand against AD. Conclusions: Selective anti-BuChE activity of the dichloromethane extract of sagapenum, as well as farnesiferol A and its good anti-BACE1 activity, may play a significant role in the development of anti-AD supplements.