Cholinesterase Inhibitory Activity, Gas Chromatography-Mass Spectrometry Profiling, and In Silico Studies on the...

In this study, the essential oils (EOs) from Artemisia campestris, A. herba-alba, and A. judaica, obtained by hydrodistillation and characterized by gas chromatography-mass spectrometry, were investigated for their inhibitory potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using a microtiter-based assay, molecular docking, molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling analysis. Major monoterpenes were docked into the active sites of AChE and BChE, and key complexes were subjected to 100 ns MD simulations and molecular mechanics generalized born surface area binding free energy calculations. In silico ADMET analysis was further performed to assess pharmacokinetic properties and drug-likeness of the most active compounds. The EOs exhibited a concentration-dependent cholinesterase inhibition. A. judaica showed the strongest AChE inhibition (half-maximal inhibitory concentration [IC₅₀] = 17.84 µg/mL), while A. campestris was the most effective against BChE (IC₅₀ = 9.82 µg/mL). Docking results revealed favorable interactions between key constituents, such as camphor and piperitone, and critical active site residues of the enzymes. MD simulations confirmed the structural stability and favorable binding of these ligands, as evidenced by low root mean square deviation fluctuations and consistent hydrogen bonding. ADMET predictions supported their oral bioavailability and low toxicity potential. These results highlight the cholinesterase inhibitory potential of three Artemisia-derived EOs and may provide an initial molecular basis for Alzheimer's disease management.