2. Academic Validation
  3. Glycyrrhizin Attenuates White Matter Injury by Inhibiting Neuroinflammation through the HMGB1/TLR4 Pathway

Glycyrrhizin Attenuates White Matter Injury by Inhibiting Neuroinflammation through the HMGB1/TLR4 Pathway

  • Mol Neurobiol. 2024 Dec 21. doi: 10.1007/s12035-024-04657-9.
Jia Lou 1,  Bingqing Ding 1,  Mingchu Fang 1,  Weiwei Xie 2,  Xinyi Wang 1,  Xingyun Wang 3,  Xiaoling Guo 4 5,  Jianghu Zhu 1 6 7
Affiliations

Affiliations

  • 1 Department of Pediatrics, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Pediatrics, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
  • 3 Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Scientific research department, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. guoxling@hotmail.com.
  • 5 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, Zhejiang, China. guoxling@hotmail.com.
  • 6 Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, Zhejiang, China.
  • 7 Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, China.
PMID: 39707121 DOI: 10.1007/s12035-024-04657-9
Abstract

White matter injury (WMI) is a common complication of preterm birth, potentially resulting in long-term behavioral and motor abnormalities. The objective of this study is to investigate the neuroprotective effects of glycyrrhizin (GLY) on WMI, and try to elucidate the potential mechanisms. In vivo chronic hypoxia-induced WMI mouse model and in vitro oxygen-glucose deprivation (OGD) induced WMI cell model were established, and the effects of GLY on WMI were explored through multiple assays, such as western blotting, immunofluorescence, immunohistochemistry, behavioral experiments, real-time quantitative polymerase chain reaction (RT-qPCR), transmission electron microscope (TEM), molecular docking, and bioinformatics analysis. The results showed that GLY facilitated the maturation and differentiation of oligodendrocytes and enhanced the thickness as well as density of myelin sheaths. GLY also reduced inflammatory response, improved memory, learning, and locomotor performances, and alleviated anxiety in WMI mice. The neuroprotective effects of GLY may be involved in the down-regulation of HMGB1 and its associated proteins such as TLR4 and NF-κB. In conclusion, GLY could mitigate chronic hypoxia-induced WMI and OGD-induced oligodendrocyte injury through its anti-inflammatory effects by inhibiting the HMGB1/TLR4 pathway, suggesting a potential therapeutic avenue for WMI.

Keywords

Glycyrrhizin (GLY); Hypoxia; Inflammation; Oligodendrocyte; White matter injury (WMI).

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