title: Luteolin reduces primary hippocampal neurons death induced by neuroinflammation.
abstract: OBJECTIVE
  This study examined whether luteolin may exert an anti-inflammatory effect in microglia and may be neuroprotective by regulating microglia activation.
  
  
  METHODS
  We treated BV2 microglia with 1.0 μg/ml lipopolysaccharide (LPS) after incubation with luteolin for 1 hour, the nitric oxide (NO) levels were determined by a Griess reaction, the inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta) mRNA expression were determined by real-time PCR analysis, the iNOS and COX-2 protein induction were determined by Western blot analysis, and the levels of prostaglandin E(2) (PGE(2)), TNF-alpha, and IL-1beta were determined by enzyme-linked immunosorbent assay (ELISA) kits. Rat primary hippocampal neurons were co-cultured with LPS-activated BV2 microglia with 20 μM luteolin for 24 hours, the hippocampal neurons viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the number of apoptotic hippocampal neurons was determined by immunofluorescence detection.
  
  
  RESULTS
  Luteolin significantly inhibited the expression of iNOS and COX-2 in LPS-induced BV2 microglia. Moreover, the compound down-regulated the proinflammatory cytokines (TNF-alpha and IL-1beta) as well as the production of NO and PGE(2) in these cells. When hippocampal neurons were co-cultured with LPS-stimulated BV2 microglia, the administration of 20 μM luteolin increased the neurons viability and reduced the number of apoptotic neurons.
  
  
  CONCLUSIONS
  These data demonstrate that anti-inflammatory activity of luteolin in microglia contributes to its neuroprotective effect and suggest that it may have a potential therapeutic application in the treatment of neurodegenerative diseases.
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.forename: Ren-Bin
authors.initials: RB
authors.lastname: Qi
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Wang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zeng
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Zhao
authors.forename: Da-Xiang
authors.initials: DX
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D047311:Luteolin