title: Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells.
abstract: OBJECTIVE
  Kaempferol, a dietary flavonoid and phyto-oestrogen, is known to have anti-inflammatory properties. Microglial activation has been implicated in various neurodegenerative diseases. Anti-inflammatory effects of kaempferol and the underlying mechanisms were investigated by using LPS-stimulated microglial BV2 cells.
  
  
  METHODS
  Cell viability was measured using MTT and neutral red assays. elisa, Western blot, immunocytochemistry and electrophoretic mobility-shift assay were used to analyse NO, PGE(2) , TNF-α and IL-1β production, inducible NOS (iNOS), COX-2 expression and the involvement of signalling pathways such as toll-like receptor-4 (TLR4), MAPK cascades, PKB (AKT) and NF-κB. Accumulation of reaction oxygen species (ROS) was measured by nitroblue tetrazolium and 2'7'-dichlorofluorescein diacetate assay. Matrix metalloproteinase activity was investigated by zymography and immunoblot assay. Phagocytotic activity was assessed by use of latex beads.
  
  
  RESULTS
  Kaempferol significantly attenuated LPS-induced NO, PGE(2) , TNF-α, IL-1β and ROS production and phagocytosis in a concentration-dependent manner. Kaempferol suppressed the expression of iNOS, COX-2, MMP-3 and blocked the TLR4 activation. Moreover, kaempferol inhibited LPS-induced NF-κB activation and p38 MAPK, JNK and AKT phosphorylation.
  
  
  CONCLUSIONS
  Kaempferol was able to reduce LPS-induced inflammatory mediators through the down-regulation of TLR4, NF-κB, p38 MAPK, JNK and AKT suggesting that kaempferol has therapeutic potential for the treatment of neuroinflammatory diseases.
authors: Department of Biotechnology, Chosun University, Gwangju, Korea.
authors: S E
authors: SE
authors: Park
authors: K
authors: K
authors: Sapkota
authors: S
authors: S
authors: Kim
authors: H
authors: H
authors: Kim
authors: S J
authors: SJ
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D044949:Kaempferols / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D044949:Kaempferols; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C006552:kaempferol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone