<i>Athamanta sicula</i> L. Root extract: <i>in vitro</i> and <i>in silico</i> 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 <i>Athamanta sicula</i> 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 <i>in vitro</i> assays, molecular docking, and ADME predictions. The crude extract demonstrated superior inhibition of <i>α</i>-amylase and <i>α</i>-glucosidase compared to acarbose. Among the isolated compounds, apiol showed more activity than myristicin, particularly against <i>α</i>-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.