18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination

Scientific Reports
Jieru ZhouRui Huang

Abstract

Microglia are intrinsic immune cells in the central nervous system (CNS). The under controlled microglia activation plays important roles in inflammatory demyelination diseases, such as multiple sclerosis (MS). However, the means to modulate microglia activation as a therapeutic modality and the underlying mechanisms remain elusive. Here we show that administration of 18β-glycyrrhetinic acid (GRA), by using both preventive and therapeutic treatment protocols, significantly suppresses disease severity of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The treatment effect of GRA on EAE is attributed to its regulatory effect on microglia. GRA-modulated microglia significantly decreased pro-inflammatory profile in the CNS through suppression of MAPK signal pathway. The ameliorated CNS pro-inflammatory profile prevented the recruitment of encephalitogenic T cells into the CNS, which alleviated inflammation-induced demyelination. In addition, GRA treatment promoted remyelination in the CNS of EAE mice. The induced remyelination can be mediated by the overcome of inflammation-induced blockade of brain-derived neurotrophic factor expression in microglia, as well as enhancing oligodendrocyte precursor cell proliferatio...Continue Reading

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Citations

Apr 2, 2016·Mediators of Inflammation·Xueli FanTao Jin
Nov 11, 2016·Molecular Neurobiology·Li DuHong-Liang Zhang
Jan 28, 2017·Expert Review of Neurotherapeutics·Ethan HollingsworthJaime Imitola
Dec 18, 2018·Journal of Cellular and Molecular Medicine·Min JinYanyun Zhang
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia A LuchnikovaIrina B Ivshina
Dec 12, 2018·International Immunopharmacology·Shuangwen YuKaili Hu

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Methods Mentioned

BETA
transmission electron microscopy
ELISA
light microscopy
PCR

Software Mentioned

SPSS
GraphPad Prism
GraphPad

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