期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 28, 期 1, 页码 578-587出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2015.07.027
关键词
Resveratrol; Hypoxia; Microglial activation; Neurotoxicity; Nuclear factor kappa B
资金
- National Natural Science Foundation of China [81200879]
- Fundamental Research Funds of Shandong University [2015JC008]
Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has been found to afford neuroprotective effects against neuroinflammation in the brain. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to hypoxic brain injuries. The aim of this study is to investigate the potential role of resveratrol in attenuating hypoxia-induced neurotoxicity via its anti-inflammatory actions through in vitro models of the BV-2 microglial cell line and primary microglia. We found that resveratrol significantly inhibited hypoxia-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, resveratrol inhibited the hypoxia-induced degradation of I kappa B-alpha and phosphorylation of p65 NF-kappa B protein. Hypoxia-induced ERK1/2 and INK phosphorylation was also strongly inhibited by resveratrol, whereas resveratrol had no effect on hypoxia-stimulated p38 MAPK phosphorylation. Importantly, treating primary cortical neurons with conditioned medium (CM) from hypoxia-stimulated microglia induced neuronal apoptosis, which was reversed by CM co-treated with resveratrol. Taken together, resveratrol exerts neuroprotection against hypoxia-induced neurotoxicity through its anti-inflammatory effects in microglia. These effects were mediated, at least in part, by suppressing the activation of NF-kappa B, ERR and JNK MAPK signaling pathways. (C) 2015 Elsevier B.V. All rights reserved.
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