Ferula haussknechtii Inhibits Acetylcholinesterase: In‐Vitro and In‐Silico Studies

Abstract

Alzheimer's disease (AD) is a destructive neurological disease. Approved therapies that target the cholinergic system to control the symptoms have various complications. Natural compounds that inhibit the acetylcholinesterase (AChE) enzyme can promote the development of new drugs. Nature‐derived compounds are more compatible with biological systems in comparison to synthetic library. Ferula haussknechtii is a native species of Iran. In study, we evaluated the effects of its essential oil and extracts on the inhibition of AChE through in vitro and in silico methods. The essential oil was extracted by Clevenger apparatus. Extracts were prepared by maceration for 72 hours. The Ellman's test was used to measure the inhibitory effects of the samples. The interaction of the main constituents of the essential oil with AChE was investigated by Coarse Grained molecular dynamics (CG‐MD) simulation. Essential oil inhibited the AChE with IC50: 44.6 μg/ml. Among different extracts, hydroalcoholic extract with IC50: 41.4 μg/ml exhibited the most potent inhibitory effect. Based on the results of 1 μs CG‐MD simulation, the major constituents of the essential oil inhibited the AChE by binding to the PAS site. The constituents of F. haussknechtii could be considered as a rich source for discovering and designing new AChE inhibitors.