title: Caffeic acid ester fraction from Erigeron breviscapus inhibits microglial activation and provides neuroprotection.
abstract: OBJECTIVE
  To investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo.
  
  
  METHODS
  The production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β mRNA in ischemic cerebral tissues.
  
  
  RESULTS
  Caf inhibited the production of NO, TNF-α and IL-1β induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Caf could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-α, and IL-1β gene expressions in ischemic cerebral tissues.
  
  
  CONCLUSIONS
  Caf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.
authors: Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin (300193), China.
authors: Shao-xia
authors: SX
authors: Wang
authors: Hong
authors: H
authors: Guo
authors: Li-min
authors: LM
authors: Hu
authors: Ya-nan
authors: YN
authors: Liu
authors: Yue-fei
authors: YF
authors: Wang
authors: Li-yuan
authors: LY
authors: Kang
authors: Xiu-mei
authors: XM
authors: Gao
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D049919:Erigeron / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C472707:caffeoylquinic acid; D011801:Quinic Acid; D052247:Nitric Oxide Synthase Type II