Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways

Neurobiol Learn Mem. 2011 Sep;96(2):156-65. doi: 10.1016/j.nlm.2011.03.010. Epub 2011 Apr 7.


Evidence indicates that systemic administration of lipopolysaccharide (LPS) induces brain inflammation, ultimately resulting in cognitive deficits. Ursolic acid (UA), a plant-derived pentacyclic triterpenoid, is well known to possess multiple biological functions, including antioxidant, anti-tumor and anti-inflammatory activities. In the present study, we assessed the protective effect of UA against the LPS-induced cognitive deficits in mice. We found that UA significantly improved cognitive deficits of LPS-treated mice in open field, step-through passive avoidance and Morris water maze tasks. One potential mechanism of this action was attributed to the decreased production of pro-inflammatory markers including COX-2, iNOS, TNF-α, IL-1β, IL-2 and IL-6 in LPS-treated mouse brain. Mechanistically, UA markedly inhibited LPS-induced IκBα phosphorylation and degradation, NF-κB p65 nuclear translocation and p38 activation in mouse brain, but did not affect the activation of TLR4, MyD88, ERK, JNK and Akt. Taken together, these results suggest that UA may be useful for mitigating inflammation-associated brain disorders by inhibiting pro-inflammatory factors production, at least in part, through blocking the p38/NF-κB signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / immunology
  • Brain / metabolism
  • Cognition / drug effects*
  • Cognition / physiology
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Triterpenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Lipopolysaccharides
  • NF-kappa B
  • Triterpenes
  • p38 Mitogen-Activated Protein Kinases
  • ursolic acid