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Protective Effect of Naringenin in Experimental Ischemic Stroke: Down-Regulated NOD2, RIP2, NF-κB, MMP-9 and Up-Regulated Claudin-5 Expression

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Abstract

Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague–Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG’s influence on blood–brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 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 Nos. C2010000564 and 10276104D). 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.

Conflict of interest

The authors declare that they have no conflict of interests.

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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

    Xue Bai, Xiangjian Zhang, Linyu Chen, Jian Zhang, Lan Zhang, Xumeng Zhao, Ting Zhao & Yuan Zhao

  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. Xue Bai
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Correspondence to Xiangjian Zhang.

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Bai, X., Zhang, X., Chen, L. et al. Protective Effect of Naringenin in Experimental Ischemic Stroke: Down-Regulated NOD2, RIP2, NF-κB, MMP-9 and Up-Regulated Claudin-5 Expression. Neurochem Res 39, 1405–1415 (2014). https://doi.org/10.1007/s11064-014-1326-y

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