title: Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways.
abstract: 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.
authors.affiliation: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province, PR China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wu
authors.forename: Zi-hui
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Zheng
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Ruan
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Qun
authors.initials: Q
authors.lastname: Shan
authors.forename: Zi-feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000097245:Ursolic Acid
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D014315:Triterpenes; D048051:p38 Mitogen-Activated Protein Kinases; D000097245:Ursolic Acid