title: Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.
abstract: 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.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. wucf@syphu.edu.cn <wucf@syphu.edu.cn>
authors.forename: Chun Fu
authors.initials: CF
authors.lastname: Wu
authors.forename: Xiu Li
authors.initials: XL
authors.lastname: Bi
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Yang
authors.forename: Jia Yang
authors.initials: JY
authors.lastname: Zhan
authors.forename: Ying Xu
authors.initials: YX
authors.lastname: Dong
authors.forename: Jin Hui
authors.initials: JH
authors.lastname: Wang
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
authors.forename: Xian
authors.initials: X
authors.lastname: Li
mesh_terms: 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*
chemical_list: 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