title: Neuroprotective effect of kaempferol glycosides against brain injury and neuroinflammation by inhibiting the activation of NF-κB and STAT3 in transient focal stroke.
abstract: BACKGROUND
  Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model.
  
  
  RESULTS
  Rats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase.
  
  
  CONCLUSIONS
  Our findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, Department of Pharmacology, West China School of Pharmacy, Sichuan University "985 Projects - Science and Technology Innovation Platform for Novel Drug Development and Translational Neuroscience Center", Chengdu, China.
authors: Lu
authors: L
authors: Yu
authors: Chu
authors: C
authors: Chen
authors: Liang-Fen
authors: LF
authors: Wang
authors: Xi
authors: X
authors: Kuang
authors: Ke
authors: K
authors: Liu
authors: Hao
authors: H
authors: Zhang
authors: Jun-Rong
authors: JR
authors: Du
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009005:Monosaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D044949:Kaempferols; D009005:Monosaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C511963:kaempferol-3-O-glucoside; C492687:kaempferol-3-O-rutinoside