Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Anti-inflammatory effects of the human milk oligosaccharide, 2’-fucosyllactose, exerted via modulation of M2 microglial activation in a mouse model of ischemia-reperfusion injury

Version 1 : Received: 11 May 2023 / Approved: 12 May 2023 / Online: 12 May 2023 (08:11:06 CEST)

A peer-reviewed article of this Preprint also exists.

Pak, M.E.; Kim, Y.-J.; Kim, H.; Shin, C.S.; Yoon, J.-W.; Jeon, S.-M.; Song, Y.-H.; Kim, K. 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. Antioxidants 2023, 12, 1281. Pak, M.E.; Kim, Y.-J.; Kim, H.; Shin, C.S.; Yoon, J.-W.; Jeon, S.-M.; Song, Y.-H.; Kim, K. 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. Antioxidants 2023, 12, 1281.

Abstract

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but 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. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

Keywords

2’-fucosyllactose, microglia polarization, anti-inflammation, reactive oxygen species, ischemic injury

Subject

Biology and Life Sciences, Food Science and Technology

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