Abstract: Echinenone, a keto carotenoid, has been extracted mainly from marine organisms such as sea urchin and algae. In this work, the inhibitory effect of echinenone on acetylcholinesterase (AChE) was studied, and the underlying mechanism was elucidated by enzyme kinetics, fluorescence spectroscopy, circular dichroism spectroscopy and molecular docking. In addition, a cell model of Alzheimer’s disease (AD) was established by inducing rat adrenal pheochromocytoma PC12 cells with amyloid beta peptide 25-35 (Aβ25-35) to study the effects of echinenone on oxidative stress injury in the AD model. The results showed that echinenone had strong inhibitory effect on AChE, with a half-maximal inhibition concentration (IC50) value of (16.29 ± 0.97) μg/mL and an inhibition constant Ki of 3.82 μg/mL, and the inhibition was competitive. Echinenone could induce changes in the secondary structure of AChE, and it was more likely to bind to Ser200, His440, Trp84 and Tyr121 in the active center of AChE, hindering the substrate acetylthiocholine iodide (ATCI) from binding to the enzyme and, consequently, resulting in a decrease of the enzyme’s activity. Echinenone inhibited the activity of AChE in PC12 cells induced by Aβ25-35, reduced the content of malondialdehyde (MDA), and increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), thus reducing oxidative stress damage of PC12 cells induced by Aβ25-35. The results of this study will provide data support and a theoretical basis for the application of echinenone in functional foods, biomedicine and other fields.

Key words: echinenone; Alzheimer’s disease; acetylcholinesterase; molecular docking; oxidative stress