Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation

Jiaxiang Shao1, Tengyuan Liu, Qian Reuben Xie

  • 1School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China.

Insights

Adjudin, a potential male contraceptive, effectively reduces neuroinflammation by inhibiting microglial activation and pro-inflammatory mediators. This compound shows promise in treating central nervous system diseases linked to inflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglial activation drives neuroinflammation in CNS diseases like ischemia and neurodegeneration.
  • Pro-inflammatory mediators released by activated microglia contribute to disease pathogenesis.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of Adjudin, a non-hormonal male contraceptive candidate.
  • To determine Adjudin's impact on microglial activation and associated inflammatory pathways.

Main Methods:

  • In vitro studies using BV2 microglial cells stimulated with LPS.
  • In vivo studies utilizing a permanent middle cerebral artery occlusion (pMCAO) mouse model.
  • Analysis of inflammatory mediator production, NF-κB and ERK MAPK signaling pathways, and microglial activation markers.

Main Results:

  • Adjudin significantly inhibited LPS-induced IL-6 release and expression of IL-6, IL-1β, and TNF-α in BV2 cells.
  • Adjudin suppressed NF-κB p65 nuclear translocation and DNA binding activity, and ERK MAPK phosphorylation.
  • In vivo, Adjudin reduced ischemia-induced CD11b expression, brain edema, and neurological deficits in pMCAO mice, without altering infarct volume.

Conclusions:

  • Adjudin demonstrates significant anti-inflammatory properties by modulating microglial activation and inflammatory signaling.
  • Adjudin may serve as a therapeutic agent for mitigating neuroinflammation in CNS disorders.

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