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.
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Authors | Shanshan Yu, Jing Zhao, Xiaoyan Wang, Shipeng Lei, Xuemei Wu, Yanlin Chen, Jingxian Wu, Yong Zhao |
Journal | Neurochemical research
(Neurochem Res)
Vol. 38
Issue 7
Pg. 1501-16
(Jul 2013)
ISSN: 1573-6903 [Electronic] United States |
PMID | 23624876
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Benzyl Alcohols
- Neuroprotective Agents
- Transcription Factors
- 4-hydroxybenzyl alcohol
- Protein Kinases
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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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