Acetylcholinesterase Inhibitory Activities of Essential Oils from Vietnamese Traditional Medicinal Plants

Abstract

Essential oils are promising as environmentally friendly and safe sources of pesticides for human use. Furthermore, they are also of interest as aromatherapeutic agents in the treatment of Alzheimer's disease, and inhibition of the enzyme acetylcholinesterase (AChE) has been evaluated as an important mechanism. The essential oils of some species in the genera Callicarpa, Premna, Vitex and Karomia of the family Lamiaceae were evaluated for inhibition of electric eel AChE using the Ellman method. The essential oils of Callicarpa candicans showed promising activity, with IC₅₀ values between 45.67 and 58.38 μg/mL. The essential oils of Callicarpa sinuata, Callicarpa petelotii, Callicarpa nudiflora, Callicarpa erioclona and Vitex ajugifolia showed good activity with IC₅₀ values between 28.71 and 54.69 μg/mL. The essential oils Vitex trifolia subsp. trifolia and Callicarpa rubella showed modest activity, with IC₅₀ values of 81.34 and 89.38, respectively. trans-Carveol showed an IC₅₀ value of 102.88 µg/mL. Molecular docking and molecular dynamics simulation were performed on the major components of the studied essential oils to investigate the possible mechanisms of action of potential inhibitors. The results obtained suggest that these essential oils may be used to control mosquito vectors that transmit pathogenic viruses or to support the treatment of Alzheimer's disease.

Keywords: Alzheimer’s; Lamiaceae; atractylone; pesticide; trans-carveol.

Figure 1

The main chemical components of essential oils.

Figure 2

Validation of the predicted structure of AChE1. (A) Binding pocket predicted by CASTp; (B) QMEAN Z−Scrores value; (C) Ramachandran plot; (D) ERRAT plot. Note: Non-glycine and non-proline residues are shown as squares; Glycine residues are shown as triangles; [A, B, L]: Residues in most favoured regions; [a, b, l, p]: Residues in additional allowed regions; [~a, ~b, ~l, ~p]: Residues in generously allowed regions; Error value*:On the error axis, two lines are drawn to indicate the confidence with which it is possible to reject regions that exceed that error value; Residue #: Indate the residue number in protein model.

Figure 3

Overlay of EeAChE and AChE1 models produced using Chimera 1.13.1; the EeAChE model is presented in apricot color; the AChE1 model is presented in cyan color.

Figure 4

Dock pose overlay of crystallographic ligands (red) with the calculated shape (gray).

Figure 5

Binding orientation of potential inhibitors at the binding site of the AChE enzyme, suggested on the basis of molecular docking studies.

Figure 5

Binding orientation of potential inhibitors at the binding site of the AChE enzyme, suggested on the basis of molecular docking studies.

Figure 5

Binding orientation of potential inhibitors at the binding site of the AChE enzyme, suggested on the basis of molecular docking studies.

Figure 6

Computational modeling of FPL calculations. The pulling pathway is aligned along the Z−axis.

Figure 7

(A) The mean force of complexes over eight independent SMD trajectories. The data were monitored every 0.1 ps; (B) The mean work of complexes during eight independent SMD trajectories.