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Pretreatment by Evodiamine is Neuroprotective in Cerebral Ischemia: Up-Regulated pAkt, pGSK3β, Down-Regulated NF-κB Expression, and Ameliorated BBB Permeability

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Abstract

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Evodiamine (Evo) has been proved to elicit a variety of biological effects through its anti-inflammatory property in the treatment of infectious disease, Alzheimer’s disease and hypoxia-induced inflammatory response. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of Evo and the underlying mechanisms. Male Institute of Cancer Research (ICR) mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly divided into five groups: Sham (sham-operated + 1 % DMSO + 0.5 % tween80), pMCAO (pMCAO + 0.9 % saline), Vehicle (pMCAO + 1 % DMSO + 0.5 % tween80), Evo-L (Vehicle + Evo 50 mg/kg) and Evo-H (Vehicle + Evo 100 mg/kg) groups. Evo was administered intragastrically twice daily for 3 days, and once again 30 min before mouse brain ischemia was induced by pMCAO. Neurological deficit, brain water content and infarct size were measured at 24 h after stroke. The expression of pAkt, pGSK3β, NF-κB and claudin-5 in ischemic cerebral cortex was analyzed by western blot and qRT-PCR. Compared with Vehicle group, Evo significantly ameliorated neurological deficit, brain water content and infarct size, upregulated the expression of pAkt, pGSK3β and claudin-5, and downregulated the nuclear accumulation of NF-κB (P < 0.05). Evo protected the brain from ischemic damage caused by pMCAO; this effect may be through upregulation of pAkt, pGSK3β and claudin-5, and downregulation of NF-κB expression.

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (Grant No. 81371287) and Hebei Province (Grant No. C2010000564). We thank technicians Ruichun Liu and Hongran Wu for their technical assistance and Prof. Yansu Guo M.D. PhD. and Weisong Duan M.D. PhD. for providing valuable suggestions.

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Authors and Affiliations

  1. Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Ting Zhao, Xiangjian Zhang, Yuan Zhao, Lan Zhang, Xue Bai, Jian Zhang, Xumeng Zhao, Linyu Chen, Lina Wang & Lili Cui

  2. Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Xiangjian Zhang

  3. Hebei Key Laboratory for Neurology, Shijiazhuang, 050000, Hebei, People’s Republic of China

    Xiangjian Zhang

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  1. Ting Zhao
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  3. Yuan Zhao
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Correspondence to Xiangjian Zhang.

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Zhao, T., Zhang, X., Zhao, Y. et al. Pretreatment by Evodiamine is Neuroprotective in Cerebral Ischemia: Up-Regulated pAkt, pGSK3β, Down-Regulated NF-κB Expression, and Ameliorated BBB Permeability. Neurochem Res 39, 1612–1620 (2014). https://doi.org/10.1007/s11064-014-1356-5

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