title: Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin injection, upregulate neurotrophins synthesis and release in hypoxia/reoxygenation rat astrocytes.
abstract: BACKGROUND
  Scutellarin (Scu) and caffeic acid ester fraction (Caf), the extracts from the traditional Chinese herb, Erigeron breviscapus, are known to ameliorate post ischemic neuronal dysfunction.
  
  
  OBJECTIVE
  Neurotrophic factors (NTFs) are essential for neuronal growth and survival. We explored the neuroprotective effect of Scu and Caf by synthesis and release of NGF, BDNF and GDNF in rat astrocytes exposed to hypoxia/reoxygenation and MACO rats. And the neuroprotection of Scu and Caf was also explored.
  
  
  METHODS
  The primary rat astrocytes were cultured in vitro. The temporal mRNA and protein expression profile during hypoxia/reoxygenation were analyzed using real-time RT-PCR and ELISA. The expression of p-CREB, p-Akt, p-MAPKs and Bax were analyzed by western blotting. Cell viability of neuro-2A was measured using CCK-8 and cell cytotoxicity was measured with LDH release.
  
  
  RESULTS
  During hypoxia/reoxygenation a similar decrease pattern of NTFs (NGF, BDNF and GDNF) was observed in both mRNA and protein; Scu and Caf enhanced the expressions of NGF, BDNF and GDNF mRNA and protein in astrocytes under hypoxia/reoxygenation condition. CREB and Akt, but not MAPKs ( p-JNK, p-ERK1/2 and p-38) may be involved in the expression of NTFs. Concomitantly, conditioned medium from astrocytes which was treated by Scu or Caf after hypo3h/Reox24h significantly reduced neurotoxicity compared with conditioned medium from hypo3h/Reox24h astrocytes alone, and they show the tendency of increased neurons viability accompanied with Bax changes.
  
  
  CONCLUSIONS
  These results indicate that the neuroprotective effect of Scu and Caf might be mediated, at least in part, via a stimulation of the production and release of NTFs through p-CREB and p-Akt signaling. Furthermore, Scu and Caf could antagonistic the hypoxia induced toxicity through astrocytes conditioned medium. Those results suggested that Scu and Caf might have therapeutic potential for stroke.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chai
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Wang
authors.forename: Yu-lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.forename: Li-min
authors.initials: LM
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Dickson
authors.initials: D
authors.lastname: Adah
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D005965:Glucuronates / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002109:Caffeic Acids; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005965:Glucuronates; D012333:RNA, Messenger; C484876:scutellarin; D047310:Apigenin; D020932:Nerve Growth Factor; D051058:Oncogene Protein v-akt; C040048:caffeic acid
keywords: Brain-derived neurotrophic factor; Caffeic acid ester fraction; Glial cell line-derived neurotrophic factor; Nerve growth factor; Neuroprotection; Scutellarin