RV09, a novel resveratrol analogue, inhibits NO and TNF-alpha production by LPS-activated microglia.
Excessive activation of microglial cells has been implicated in various neurodegenerative diseases. Resveratrol, a polyphenolic compound found in grapes and wine, has been reported to reduce the activation of microglia. In the present study, 5-[2-(4-bromothiophen-2-yl)vinyl]benzene-1,3-diol (RV09), a novel resveratrol analogue, was found to suppress NO production by LPS-activated N9 microglial cell line and/or cultured rat cortical microglia. RV09 appeared to have a slight NO-scavenging activity in sodium nitroprusside (SNP) solution. The inhibition of iNOS was also observed, suggesting the blockage of transcriptional levels. Moreover, RV09 attenuated the expression of mRNA and protein of tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner. Further studies revealed that RV09 blocked IkappaBalpha phosphorylation and degradation, as well as reactive oxygen species (ROS) production in N9 microglial cells. It was also found that RV09 is a effective scavenger for 2,2-diphenyl-1-picrylhydrazyl (DPPH) used as a general free radical model. In the summary, these data suggest that, by blocking IkappaBalpha phosphorylation and degradation, RV09 acts to suppress the LPS-induced NO and TNF-alpha production in microglia, and this effect was mediated, at least in part, by inhibiting the generation of ROS. Our results suggested that RV09 is a novel anti-inflammatory agent which can inhibit proinflammatory responses of microglia.
Meng
Xue Lian
XL
Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Yang
Jing Yu
JY
Chen
Guo Liang
GL
Zhang
Li Jia
LJ
Wang
Li Hui
LH
Li
Jie
J
Wang
Ji Ming
JM
Wu
Chun Fu
CF
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000975:Antioxidants; D008070:Lipopolysaccharides; C531164:RV09 compound; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000077185:Resveratrol