Resveratrol inhibits nitric oxide and TNF-alpha production by lipopolysaccharide-activated microglia.
Upon activation, brain macrophages, the microglia, release proinflammatory mediators that play important roles in eliciting neuroinflammatory responses associated with neurodegenerative diseases. As resveratrol, an antioxidant component of grape, has been reported to exert anti-inflammatory activities on macrophages, we investigated its effects on the production of TNF-alpha (TNF-alpha) and nitric oxide (NO) by lipopolysaccharide (LPS)-activated microglia. Exposure of cultured rat cortical microglia and a mouse microglial cell line N9 to LPS increased their release of TNF-alpha and NO, which was significantly inhibited by resveratrol. Further studies revealed that resveratrol suppressed LPS-induced degradation of IkappaBalpha, expression of iNOS and phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in N9 microglial cells. These results demonstrate a potent suppressive effect of resveratrol on proinflammatory responses of microglia, suggesting a therapeutic potential for this compound in neurodegenerative diseases accompanied by microglial activation.
Bi
Xiu Li
XL
Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Yang
Jing Yu
JY
Dong
Ying Xu
YX
Wang
Ji Ming
JM
Cui
Yong Hong
YH
Ikeshima
Takashi
T
Zhao
Yu Qing
YQ
Wu
Chun Fu
CF
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D009573:Nitrites; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D000077185:Resveratrol