Athamanta sicula L. Root extract: in vitro and in silico evaluation of anti-diabetic and anti-Alzheimer’s activities of apiol and myristicin

This study is the first to analyse the methanolic root extract of Athamanta sicula L., an endemic Mediterranean plant, leading to the isolation of two phenylpropanoids: apiol and myristicin. The extract and isolated compounds were evaluated for their inhibitory potential against α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) using in vitro assays, molecular docking, and ADME predictions. The crude extract demonstrated superior inhibition of α-amylase and α-glucosidase compared to acarbose. Among the isolated compounds, apiol showed more activity than myristicin, particularly against α-glucosidase. Both compounds inhibited BChE, with apiol (IC50 = 330.07 µM; MolDock score = −89.89) outperforming myristicin (IC50 = 385.08 µM; MolDock score = −87.86). Favourable ADME properties, including high gastrointestinal absorption and blood-brain barrier penetration, were also predicted. These findings suggest that apiol and myristicin are key contributors to the plant’s bioactivity, making them promising multi-target lead compounds for developing new treatments for diabetes and Alzheimer’s disease.