title: 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.
authors.affiliation: Department of Pathology, Chongqing Medical University, Yixueyuan Road 1, Chongqing, 400016, People's Republic of China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Shipeng
authors.initials: S
authors.lastname: Lei
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wu
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Chen
authors.forename: Jingxian
authors.initials: J
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001592:Benzyl Alcohols / Q000494:pharmacology*; D002478:Cells, Cultured; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001592:Benzyl Alcohols; D018696:Neuroprotective Agents; D014157:Transcription Factors; C018966:4-hydroxybenzyl alcohol; D011494:Protein Kinases