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: Chun Fu Wu, Xiu Li Bi, Jing Yu Yang, Jia Yang Zhan, Ying Xu Dong, Jin Hui Wang, Ji Ming Wang, Ruiwen Zhang, Xian Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 7 Issue 3 Pg. 313-20 (Mar 2007) ISSN: 1567-5769 [Print] Netherlands
• PMID: 17276889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ginsenosides
• I-kappa B Proteins
• Lipopolysaccharides
• NF-kappa B
• Nfkbia protein, mouse
• Tumor Necrosis Factor-alpha
• NF-KappaB Inhibitor alpha
• Nitric Oxide
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Cells, Cultured
• Ginsenosides (pharmacology)
• I-kappa B Proteins (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Microglia (drug effects, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Nitric Oxide (biosynthesis)
• Phosphorylation
• Tumor Necrosis Factor-alpha (biosynthesis)