title: Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia.
abstract: BACKGROUND
  Inflammatory damage is known to be involved in ischemic stroke. Luteolin has been proved to elicit a series of biologic effects through its anti-inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigate the potential neuroprotective role of luteolin in ischemic stroke and the underlying mechanisms.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to pMCAO and luteolin was administered intraperitoneally immediately after surgery, then once daily thereafter. Neurological deficit, infarct volume, and brain water content were measured at 24 h and 72 h after stroke. The expression of TLR4, TLR5, and NF-κB were measured by real-time PCR, immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular signal-regulated kinase (ERK) were detected by IHC, and Western blot.
  
  
  RESULTS
  Compared with pMCAO group, luteolin significantly alleviated neurological deficit, decreased infarct volume and suppressed edema after ischemic stroke, which were accompanied with decreased expression of TLR4, TLR5, NF-κB and p-p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05).
  
  
  CONCLUSIONS
  Luteolin protected the brain from the damage caused by pMCAO, and this effect may be through downregulation of TLR4, TLR5, NF-κB, p38MAPK and upregulation of ERK expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiao
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Lipeng
authors.initials: L
authors.lastname: Dong
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Xing
authors.forename: Chaohui
authors.initials: C
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Ji
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control; D016328:NF-kappa B / Q000096:biosynthesis*; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D047311:Luteolin