Myricitrin blocks activation of NF-κB and MAPK signaling pathways to protect nigrostriatum neuron in LPS-stimulated mice

J Neuroimmunol. 2019 Dec 15;337:577049. doi: 10.1016/j.jneuroim.2019.577049. Epub 2019 Sep 3.

Abstract

Myricitrin, a bioactive and natural flavonoids, is well known for its anti-inflammatory and antioxidant properties. However, the anti-neuroinflammation and possible mechanism has not been fully elucidated. Therefore, the present study was to investigate the possible mechanism of its neuroprotection and anti-neuroinflammation in the nigrostriatum of LPS-stimulated mice. The results showed that myricitrin improved neuron injury and raised the expressions of PSD-95 protein and TH protein in the nigrostriatum of LPS-stimulated mice. In addition, myricitrin decreased the production of pro-inflammatory factors including IL-1β, IL-6 and TNFα, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS. Meanwhile, myricitrin suppressed HMGB1, TLR4, and MyD88 expression in the nigrostriatum of LPS-stimulated mice. Furthermore, myricitrin inhibited NF-κB and MAPK signaling pathways activated by LPS. In conclusion, our studies suggest that myricitrin blocks activation of protects NF-κB and MAPK signaling pathways to nigrostiatum neuron from injury in LPS-stimulated mice and is beneficial to treatment nigrostriatum inflammation of PD.

Keywords: Lipopolysaccharide (LPS); MAPK; Myricitrin; NF-κB; Neuroinflammation; Nigrostriatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • Lipopolysaccharides / toxicity*
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neuroprotection / drug effects
  • Neuroprotection / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism

Substances

  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • myricitrin