title: Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice.
abstract: BACKGROUND
  Oxidative and inflammatory damages have been suggested to play an important role in cerebral ischemic pathogenesis, and provide promising therapeutic strategies for stroke. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a pleiotropic transcription factor, has been shown to play a key role in protecting cells against oxidative injury in cerebral ischemia. In this study, we demonstrated the hypothesis that ursolic acid (UA), a natural pentacyclic triterpenoid acid, isolated from edible plants in the Oleaceae family, a well-known anti-oxidative and anti-inflammatory reagent, protects the brain against ischemic injury by activating the Nrf2 pathway.
  
  
  METHODS
  Nrf2(-/-) and wild-type (WT) mice were induced into focal cerebral ischemia by transient middle cerebral artery occlusion (MCAO), and received UA treatment immediately after MCAO. The behavioral dysfunction, infarct size, and the expression of Nrf2, HO-1 and inflammatory factors (TLR4 and NF-κB) in ischemic brain were measured at 24h after stroke.
  
  
  RESULTS
  UA treatment significantly improved neurological deficit and reduced infarct size in WT mice after MCAO. Administration of UA also decreased the product of lipid peroxidation, promoted the activation of Nrf2 pathway and decreased the expression of TLR4 and NF-KB after stroke in WT mice. However, Nrf2(-/-) mice demonstrated more severe neurologic deficits, infarct size and inflammatory damage after MCAO, and did not benefit from the protective effect of UA.
  
  
  CONCLUSIONS
  The results indicated that UA protected the brain against ischemic injury in mice by anti-oxidative and anti-inflammatory effects after MCAO. Activation of the Nrf2 pathway contributes to the neuroprotective effects induced by UA in cerebral ischemia.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Litao
authors.initials: L
authors.lastname: Li
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Haichao
authors.initials: H
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Du
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use*; D000097245:Ursolic Acid; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D051547:Heme Oxygenase-1; D008315:Malondialdehyde; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D000097245:Ursolic Acid; D000097782:NF-kappaB-Inducing Kinase; C495636:Nfe2l2 protein, mouse; C493487:Tlr4 protein, mouse; C496542:Hmox1 protein, mouse