Therapeutic Insights Into Alkanna tinctoria Phytochemicals as Cholinesterase Inhibitor for Alzheimer's Disease

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Alzheimer's disease (AD) poses a substantial challenge in the management of neurodegenerative disorders, necessitating innovative therapeutic strategies. Previous studies indicated that dual‐target cholinesterase inhibitors, which obstruct both AChE and BuChE, may offer therapeutic advantages in AD. This study aimed to determine the potential contribution of cholinesterase inhibitory activity of phytocompounds derived from Alkanna tinctoria as prospective anti‐Alzheimer agents. We employed an in silico docking methodology to investigate the cholinesterase inhibitory activity of A. tinctoria extracts. The present study revealed that flavonoid derivatives, specifically kaempferol‐3‐rutinoside and quercetin‐3‐glucopyranoside, exhibited considerable inhibitory effects on AChE, with docking scores of −13.233 and −12.566 kcal/mol, respectively, and on BuChE, with docking scores of −11.827 and −11.529 kcal/mol, in comparison to conventional AD treatments (donepezil and huprine19). The compounds were further assessed for pharmacokinetic characteristics and toxicity, demonstrating favorable ADMET profiles indicative of high oral bioavailability and low toxicity, which are crucial for therapeutic use. Molecular dynamics (MD) simulations further corroborated the robustness of these ligand–enzyme interactions, demonstrating their stability over time and enhancing their potential for prolonged utilization. These compounds initiated pathways for viable in vitro/in vivo experiments to determine the clinical effectiveness of these medicines.