Cargando…

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2′-fucosyllactose (2′-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aime...

Descripción completa

Detalles Bibliográficos
Autores principales: Pak, Malk Eun, Kim, Yeon-Ji, Kim, Hanhae, Shin, Chul Soo, Yoon, Jong-Won, Jeon, Seon-min, Song, Young-Ha, Kim, Kyungho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295539/
https://www.ncbi.nlm.nih.gov/pubmed/37372011
http://dx.doi.org/10.3390/antiox12061281
_version_ 1785063445153972224
author Pak, Malk Eun
Kim, Yeon-Ji
Kim, Hanhae
Shin, Chul Soo
Yoon, Jong-Won
Jeon, Seon-min
Song, Young-Ha
Kim, Kyungho
author_facet Pak, Malk Eun
Kim, Yeon-Ji
Kim, Hanhae
Shin, Chul Soo
Yoon, Jong-Won
Jeon, Seon-min
Song, Young-Ha
Kim, Kyungho
author_sort Pak, Malk Eun
collection PubMed
description Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2′-fucosyllactose (2′-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2′-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2′-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2′FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2′-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2′-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2′-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2′-FL increased IL-4 levels and activated STAT6. Our data show that 2′-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2′-FL is a potentially effective therapeutic agent for ischemic stroke.
format Online
Article
Text
id pubmed-10295539
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102955392023-06-28 Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury Pak, Malk Eun Kim, Yeon-Ji Kim, Hanhae Shin, Chul Soo Yoon, Jong-Won Jeon, Seon-min Song, Young-Ha Kim, Kyungho Antioxidants (Basel) Article Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2′-fucosyllactose (2′-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2′-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2′-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2′FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2′-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2′-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2′-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2′-FL increased IL-4 levels and activated STAT6. Our data show that 2′-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2′-FL is a potentially effective therapeutic agent for ischemic stroke. MDPI 2023-06-15 /pmc/articles/PMC10295539/ /pubmed/37372011 http://dx.doi.org/10.3390/antiox12061281 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pak, Malk Eun
Kim, Yeon-Ji
Kim, Hanhae
Shin, Chul Soo
Yoon, Jong-Won
Jeon, Seon-min
Song, Young-Ha
Kim, Kyungho
Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title_full Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title_fullStr Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title_full_unstemmed Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title_short Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2′-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia–Reperfusion Injury
title_sort anti-neuroinflammatory effects of the human milk oligosaccharide, 2′-fucosyllactose, exerted via modulation of m2 microglial activation in a mouse model of ischemia–reperfusion injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295539/
https://www.ncbi.nlm.nih.gov/pubmed/37372011
http://dx.doi.org/10.3390/antiox12061281
work_keys_str_mv AT pakmalkeun antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT kimyeonji antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT kimhanhae antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT shinchulsoo antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT yoonjongwon antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT jeonseonmin antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT songyoungha antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury
AT kimkyungho antineuroinflammatoryeffectsofthehumanmilkoligosaccharide2fucosyllactoseexertedviamodulationofm2microglialactivationinamousemodelofischemiareperfusioninjury