title: Resveratrol attenuates hypoxia-induced neurotoxicity through inhibiting microglial activation.
abstract: 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.
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Guangheng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiu
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, PR China. Electronic address: Wangzhen@sdu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: Liudexiang@sdu.edu.cn.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol
keywords: Hypoxia; Microglial activation; Neurotoxicity; Nuclear factor κB; Resveratrol