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Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK

Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclea...

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Autores principales: Yang, Xia, Guo, An-Lei, Pang, Yi-Peng, Cheng, Xiao-Jing, Xu, Ting, Li, Xin-Rui, Liu, Jiao, Zhang, Yu-Yun, Liu, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356379/
https://www.ncbi.nlm.nih.gov/pubmed/30609815
http://dx.doi.org/10.3390/md17010024
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author Yang, Xia
Guo, An-Lei
Pang, Yi-Peng
Cheng, Xiao-Jing
Xu, Ting
Li, Xin-Rui
Liu, Jiao
Zhang, Yu-Yun
Liu, Yi
author_facet Yang, Xia
Guo, An-Lei
Pang, Yi-Peng
Cheng, Xiao-Jing
Xu, Ting
Li, Xin-Rui
Liu, Jiao
Zhang, Yu-Yun
Liu, Yi
author_sort Yang, Xia
collection PubMed
description Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.
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spelling pubmed-63563792019-02-05 Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK Yang, Xia Guo, An-Lei Pang, Yi-Peng Cheng, Xiao-Jing Xu, Ting Li, Xin-Rui Liu, Jiao Zhang, Yu-Yun Liu, Yi Mar Drugs Article Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice. MDPI 2019-01-03 /pmc/articles/PMC6356379/ /pubmed/30609815 http://dx.doi.org/10.3390/md17010024 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Xia
Guo, An-Lei
Pang, Yi-Peng
Cheng, Xiao-Jing
Xu, Ting
Li, Xin-Rui
Liu, Jiao
Zhang, Yu-Yun
Liu, Yi
Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title_full Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title_fullStr Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title_full_unstemmed Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title_short Astaxanthin Attenuates Environmental Tobacco Smoke-Induced Cognitive Deficits: A Critical Role of p38 MAPK
title_sort astaxanthin attenuates environmental tobacco smoke-induced cognitive deficits: a critical role of p38 mapk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356379/
https://www.ncbi.nlm.nih.gov/pubmed/30609815
http://dx.doi.org/10.3390/md17010024
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