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4-Hydroxybenzyl alcohol confers neuroprotection through up-regulation of antioxidant protein expression.

Abstract
An herb-derived phenolic compound, 4-hydroxybenzyl alcohol (4-HBA), exhibits beneficial effects in cerebral ischemic injury. However, the molecular mechanisms underlying this observation remain unclear. Here we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) and an in vivo ischemic model of middle cerebral artery occlusion to investigate the relevant neuroprotective mechanisms. We demonstrated that 4-HBA reduced the neuronal injury, LDH release, and up-regulation of 8-hydroxydeoxyguanosine (8-OHdG) induced by OGD/R. Furthermore, 4-HBA reduced the cerebral infarct size and improved the behavioral parameters after cerebral ischemia. These neuroprotective effects may be conferred by the 4-HBA mediated upregulation of the transcription factor nuclear factor E2-related factor 2 (Nrf2), peroxiredoxin 6 (Prdx6) and protein disulfide isomerase (PDI) by the use of 4-HBA. Interestingly, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, blocked the increase in phosphorylation of Akt and abolished the neuroprotection associated with 4-HBA. Our results suggested that 4-HBA protects neurons against cerebral ischemic injury, and this neuroprotection may occur through upregulation of Nrf2, Prdx6, and PDI expression via the PI3K/Akt pathway.
AuthorsShanshan Yu, Jing Zhao, Xiaoyan Wang, Shipeng Lei, Xuemei Wu, Yanlin Chen, Jingxian Wu, Yong Zhao
JournalNeurochemical research (Neurochem Res) Vol. 38 Issue 7 Pg. 1501-16 (Jul 2013) ISSN: 1573-6903 [Electronic] United States
PMID23624876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Benzyl Alcohols
  • Neuroprotective Agents
  • Transcription Factors
  • 4-hydroxybenzyl alcohol
  • Protein Kinases
Topics
  • Animals
  • Antioxidants (metabolism)
  • Benzyl Alcohols (pharmacology)
  • Cells, Cultured
  • Male
  • Neuroprotective Agents (pharmacology)
  • Protein Kinases (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors (metabolism)
  • Up-Regulation (drug effects)

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