title: Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia.
abstract: BACKGROUND
  In response to cerebral ischemia, activated microglia release excessive inflammatory mediators which contribute to neuronal damage. Therefore, inhibition of microglial over-activation could be a therapeutic strategy to alleviate various microglia-mediated neuroinflammation. This study was aimed to elucidate the anti-inflammatory effects of Scutellarin and Edaravone given either singly, or in combination in activated microglia in rats subjected to middle cerebral artery occlusion (MCAO), and in lipopolysaccharide (LPS)-induced BV-2 microglia. Expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS) was assessed by immunofluorescence staining and Western blot. Reactive oxygen species (ROS) and nitric oxide (NO) levels were determined by flow cytometry and fluorescence microscopy, respectively.
  
  
  RESULTS
  In vivo, both Edaravone and Scutellarin markedly reduced the infarct cerebral tissue area with the latter drug being more effective with the dosage used; furthermore, when used in combination the reduction was more substantial. Remarkably, a greater diminution in distribution of activated microglia was observed with the combined drug treatment which also attenuated the immunoexpression of TNF-α, IL-1β and iNOS to a greater extent as compared to the drugs given separately. In vitro, both drugs suppressed upregulated expression of inflammatory cytokines, iNOS, NO and ROS in LPS-induced BV-2 cells. Furthermore, Edaravone and Scutellarin in combination cumulatively diminished the expression levels of the inflammatory mediators being most pronounced for TNF-α as evidenced by Western blot.
  
  
  CONCLUSIONS
  The results suggest that Edaravone and Scutellarin effectively suppressed the inflammatory responses in activated microglia, with Scutellarin being more efficacious within the dosage range used. Moreover, when both drugs were used in combination, the infarct tissue area was reduced more extensively; also, microglia-mediated inflammatory mediators notably TNF-α expression was decreased cumulatively.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.forename: Hao
authors.initials: H
authors.lastname: Zha
authors.forename: Parakalan
authors.initials: P
authors.lastname: Rangarajan
authors.forename: Eng-Ang
authors.initials: EA
authors.lastname: Ling
authors.forename: Chunyun
authors.initials: C
authors.lastname: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D005965:Glucuronates / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D008070:Lipopolysaccharides; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005965:Glucuronates; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C484876:scutellarin; D009569:Nitric Oxide; D047310:Apigenin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000077553:Edaravone; D000983:Antipyrine