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4-Hydroxybenzyl Alcohol Confers Neuroprotection Through Up-Regulation of Antioxidant Protein Expression

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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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Acknowledgments

This work was supported by grants from National Nature Science Foundation of China (No. 81070917 and 81271460). The authors wish to thank Dr. Xiu-Wu Bian and Dr You-Hong Cui (Third Military Medical University, Chongqing, China) for their support and advice in the cell culture experiments.

Conflict of interest

The authors declare no conflict of interest exists.

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Authors and Affiliations

  1. Department of Pathology, Chongqing Medical University, Yixueyuan Road 1, Chongqing, 400016, People’s Republic of China

    Shanshan Yu, Xiaoyan Wang, Xuemei Wu, Yanlin Chen, Jingxian Wu & Yong Zhao

  2. Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shanshan Yu, Jing Zhao, Xiaoyan Wang, Xuemei Wu, Yanlin Chen, Jingxian Wu & Yong Zhao

  3. Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shanshan Yu, Jing Zhao, Xiaoyan Wang, Xuemei Wu, Yanlin Chen, Jingxian Wu & Yong Zhao

  4. Department of Pathophysiology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Jing Zhao

  5. Department of Respiratory Medicine, Jiangjin Center Hospital, Chongqing, 402260, People’s Republic of China

    Shipeng Lei

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  1. Shanshan Yu
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Correspondence to Yong Zhao.

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Yu, S., Zhao, J., Wang, X. et al. 4-Hydroxybenzyl Alcohol Confers Neuroprotection Through Up-Regulation of Antioxidant Protein Expression. Neurochem Res 38, 1501–1516 (2013). https://doi.org/10.1007/s11064-013-1052-x

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  • DOI: https://doi.org/10.1007/s11064-013-1052-x

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