Distichochlamys citrea essential oil alleviates trimethyltin-induced cognitive dysfunction and neurodegeneration through modulation of acetylcholinesterase activity.

Cholinesterase inhibitor medications have been a key pharmacological inter-vention for managing memory-related symptoms; however, intolerable side effects are associated with their use. Aromatherapy that bypasses first-pass metabolism can be a low-risk approach. This study aimed to investigate whether inhalation of DCEO can reverse memory impairment in a mouse model of trimethyltin (TMT)-induced amnesia. TMT mice displayed anxiety-like behaviors and memory deficits assessed by open field test, Y-maze, novel object recognition test and morris water maze, which were alleviated by daily inhalation of DCEO for 15 days. Our histological analysis revealed that DCEO significantly decreased the number of degenerating nerve cells in the CA3/Hilus regions of TMT mice. DCEO exhibited strong inhibitory activity against acetylcholin-esterase (AChE) in vitro, with an IC50 of 32.01 ± 1.41 µg/ mL, which may partly explain the reduced AChE activity in the hippocampus of TMT mice treated with DCEO. Molecular docking showed that main constituents of DCEO including 1,8-cinenole, (Z)-citral, (E)-citral, and geraniol had a good affinity for AChE binding through interactions with catalytic and peripheral anionic site residues. These data suggest that neuroprotective effects of DCEO may be associated with modulation of AChE activity, making it likely a promising alterna-tive and complementary treatment to rescue memory and neuronal damage.