title: Butein provides neuroprotective and anti-neuroinflammatory effects through Nrf2/ARE-dependent haem oxygenase 1 expression by activating the PI3K/Akt pathway.
abstract: Butein, 3,4,2',4'-tetrahydroxychalcone, has various pharmacological effects. However, no study has demonstrated the specific neurobiological mechanisms of the effects of butein in neuronal cells. The present study examined the role of butein as an antioxidative and anti-inflammatory inducer of haem oxygenase 1 (HO1) in mouse hippocampal HT22, BV2 microglial and primary mouse hippocampus neurons.
  
  
  
  We investigated the neuroprotective effects of butein on glutamate-induced HT22 cell and primary mouse hippocampal neuron death and its anti-neuroinflammatory effects on LPS-induced activation of BV2 cells. We elucidated the underlying mechanisms by assessing the involvement of NF-κB, HO1, nuclear factor-E2-related factor 2 (Nrf2) and Akt signalling.
  
  
  
  Butein decreased cellular oxidative injury and the production of ROS in glutamate-treated HT22 cells and primary mouse hippocampal neurons. Furthermore, butein suppressed LPS-induced pro-inflammatory enzymes and mediators in BV2 microglia. Butein inhibited IL-6, IL-1β and TNF-α production and mRNA expression. In addition, butein decreased NO and PGE2 production and inducible NOS and COX-2 expression through the NF-κB signalling pathway. Butein up-regulated Nrf2/ARE-mediated HO1 expression through the PI3K/Akt pathway and this was positively associated with its cytoprotective effects and anti-neuroinflammatory actions.
  
  
  
  Our results indicate that butein effectively prevents glutamate-induced oxidative damage and LPS-induced activation and that the induction of HO1 by butein through the PI3K/Akt pathway and Nrf2 activation appears to play a pivotal role in its effects on neuronal cells. Our results provide evidence for the neuroprotective properties of butein.
authors.affiliation: College of Pharmacy, Chosun University, Gwangju, Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Keimyung University, Daegu, Korea. gsjeong@kmu.ac.kr.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; C040918:butein; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt