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Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.

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 ?M. 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.

SUBMITTER: Lin J

PROVIDER: S-EPMC4849071 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.

Lin Jiajia J Huang Ling L Yu Jie J Xiang Siying S Wang Jialing J Zhang Jinrong J Yan Xiaojun X Cui Wei W He Shan S Wang Qinwen Q

Marine drugs 20160325 4

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 neur ...[more]

PMID: 27023569

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Project description:Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells. The potent EA fraction then investigated and confirmed for its involvement of HO-1 pathway using hemin (HO-1 inducer) and ZnPP (HO-1 inhibitor) through Western blotting, DCFH-DA, and/or Griess assay. The involvements of PI3K/Akt, MEK, and p38 MAPK also investigated. Furthermore, we applied EA fraction to the animals at 100 and 200 mg/kg doses to check if the extract could improve scopolamine-induced memory deficits in passive avoidance and elevated plus maze tests. Our results demonstrated that the fractions from PAF significantly inhibited the generation of intracellular reactive oxygen species (ROS) induced by LPS in concentration-dependent manners. In comparison to other fractions, the EA fraction exhibited potent effect in suppressing intracellular ROS generation. Besides, EA fraction also induced the expression of HO-1 in time- and concentration-dependent manners. ZnPP significantly reversed the suppressive effect of EA fraction on LPS-induced ROS generation and NO production, which confirm the involvement of HO-1 signaling in EA-fraction-mediated antioxidant activities. Consistently, blocking of PI3K/Akt, MEK, and p38 MAPK pathways by PAF-EA suppressed the production of intracellular ROS, indicating their potential participation. In addition, one of the major constituents of EA fraction, luteolin-7-O-?-D-glucoside, also demonstrated HO-1-dependent antioxidant effects in BV2 cells. Further, the EA fraction significantly (p?<?0.05) improves scopolamine-induced memory deficits in mice. Taken together, our findings highlight the antioxidant effects of EA fraction of PAF which may be beneficial in treatment of different neurodegenerative diseases associated with free radicals.

Dataset Information

Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.

Publications

Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro.

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