Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.
Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS-activated N9 cells. Ginsenoside-Rg1 and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-alpha and NO induction, the effect of ginsenosides on transcription factor NF-kappaB protein level was also examined. These activities were associated with the down-regulation of inhibitor kappaB (IkappaB). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation.
Wu
Chun Fu
CF
Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. wucf@syphu.edu.cn <wucf@syphu.edu.cn>
Bi
Xiu Li
XL
Yang
Jing Yu
JY
Zhan
Jia Yang
JY
Dong
Ying Xu
YX
Wang
Jin Hui
JH
Wang
Ji Ming
JM
Zhang
Ruiwen
R
Li
Xian
X
D000818:Animals; D002478:Cells, Cultured; D036145:Ginsenosides / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D036145:Ginsenosides; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases