title: Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.
abstract: BACKGROUND
  Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation.
  
  
  METHODS
  In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1β and IL-6 genes) and NO synthesis were also examined.
  
  
  RESULTS
  Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1α (HIF-1α) significantly increase, while the cytosol IκB-α content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IκB-α protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-κB activation and reduce the HIF-1α generation.
  
  
  CONCLUSIONS
  These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-κB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-α pathway.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiow-Yunn
authors.initials: SY
authors.lastname: Sheu
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hong
authors.affiliation: Department of Orthopedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, No.25, Lane 442, Sec. 1, Jingguo Rd., Hsin-Chu City, 30059, Taiwan. drjssun@gmail.com.|Department of Orthopedic Surgery, College of Medicine, National Taiwan University, No. 1, Sec. 1, Ren-Ai Rd., Taipei, 10051, Taiwan. drjssun@gmail.com.|Biomimetic Systems Research Center, National Chiao Tung University, Hsin-Chu, Taiwan. drjssun@gmail.com.
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Sun
authors.affiliation: Department of Food Science, College Health Science and Technology, China University of Science and Technology, Taipei, Taiwan.
authors.forename: Man-Hai
authors.initials: MH
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Biomimetic Systems Research Center, National Chiao Tung University, Hsin-Chu, Taiwan.
authors.forename: Cherng-Jyh
authors.initials: CJ
authors.lastname: Ke
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D032266:Scrophularia / Q000737:chemistry*
chemical_list: D006027:Glycosides; D010936:Plant Extracts; D020011:Protective Agents; D011714:Pyrans; C033249:harpagoside