In vitro and in silico inhibition of acetylcholinesterase by acetone extracts of Anvillea garcinii subsp. radiata (Coss. & Durieu) Anderb., Marrubium deserti (de Noé) Coss., and Asphodelus tenuifolius Cav. from the Algerian desert.

The complex pathophysiology of Alzheimer's disease underscores the need for potent AChE inhibitors. In this context, we investigated, for the first time, the acetone extracts of three Algerian medicinal plants: Anvillea garcinii subsp. radiata (Coss. & Durieu) Anderb., Marrubium deserti (de Noé) Coss., and Asphodelus tenuifolius Cav., through combined in vitro AChE assays, LC-MS/MS metabolite profiling and in silico evaluation. Total phenolic and flavonoid content analyses revealed that M. deserti had the highest levels TPC/TFC (209.8 ± 0.6 mgGAE/g and 161.0 ± 0.9 mgQE/g, respectively). In vitro AChE inhibition assays, showed that galantamine exhibited the strongest activity (4.23 ± 0.02 μg/mL) followed by the A. garcinii subsp. radiata (IC₅₀=122.88 ± 1.30 µg/mL). LC-MS/MS profiling identified 21 compounds, with A. garcinii subsp. radiata displaying the most diverse chemical profile. Molecular docking analysis revealed strong binding affinities, with hesperidin exhibiting the highest binding energy (-11.2 kcal/mol), comparable to the reference drug donepezil (-11.5 kcal/mol).