Abstract
Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer’s disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression.
Highlights
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders leading to cognitive impairments [1]
Chemical structure of fucoxanthin; (B) low‐energy conformation of fucoxanthin mainly bound to the (A) Chemical structure of fucoxanthin; (B) low-energy conformation of fucoxanthin mainly bound to peripheral anionic site (PAS) of AChE generated by molecular docking
We have reported for the first time that fucoxanthin, a carotenoid extracted extracted from brown seaweeds, can effectively reverse scopolamine‐induced impairments of from brown seaweeds, can effectively reverse scopolamine-induced impairments of cognition in mice, cognition in mice, suggesting that fucoxanthin might be used in the treatment of AD
Summary
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders leading to cognitive impairments [1]. Scopolamine induces cognitive impairment associated with an attenuation of cholinergic neurotransmission, as well as increased oxidative stress and inflammation in the brain [9,10]. Drugs that can effectively enhance cholinergic transmission and/or reduce oxidative stress and inflammation might reverse scopolamine‐induced cognitive impairments [11].inflammation might reverse scopolamine-induced transmission and/or reduce oxidative stress and Marine carotenoids are widely present in both plants and animals. Recent study has shown that fucoxanthin can ameliorate Aβ‐induced antioxidant enzymes oxidative stress inamicroglia cells, be usefulAβ-induced for the treatment of Interestingly, recent study hassuggesting shownthat thatfucoxanthin fucoxanthin might can ameliorate oxidative. In this cells, study, we first that evaluated the might effectsbeofuseful fucoxanthin on scopolamine‐induced stress[20]. Themolecular molecular docking basis of the interaction between fucoxanthin and AChE by molecular docking simulation
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