Resveratrol attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation

• Published in: International immunopharmacology 2015-09, Vol.28 (1), p.578-587
• Main Authors: Zhang, Qun, Yuan, Lin, Zhang, Qingrui, Gao, Yan, Liu, Guangheng, Xiu, Meng, Wei, Xiang, Wang, Zhen, Liu, Dexiang
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cells, Cultured; Hypoxia; Hypoxia - complications; Hypoxia - metabolism; Interleukin-1beta - metabolism; Mice; Microglia - drug effects; Microglia - metabolism; Microglial activation; Mitogen-Activated Protein Kinases - metabolism; Neuroprotective Agents - pharmacology; Neurotoxicity; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nuclear factor κB; Resveratrol; Stilbenes - pharmacology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2015.07.027

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 IκB-alpha and phosphorylation of p65 NF-κB protein. Hypoxia-induced ERK1/2 and JNK 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-ĸB, ERK and JNK MAPK signaling pathways. •Resveratrol inhibited hypoxia-induced microglial activation.•Resveratrol prevented hypoxia-induced release of pro-inflammatory factors.•Resveratrol suppressed activation of NF-ĸB, ERK and JNK MAPK.