Ginsenoside Rh1 suppresses inducible nitric oxide synthase gene expression in IFN-γ-stimulated microglia via modulation of JAK/STAT and ERK signaling pathways

Ji Sun Jung, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Microglial activation plays an important role in the pathogenesis of various neurodegenerative diseases by producing neurotoxic factors, such as pro-inflammatory cytokines and nitric oxide (NO). In the present study, we found that protopanaxatriol ginsenoside Rh1 suppresses NO, ROS, and TNF-α production in IFN-γ-stimulated BV2 microglial cells. Rh1 inhibited the mRNA and protein expression of iNOS and TNF-α. To determine the regulatory mechanism of iNOS gene expression by Rh1, promoter analysis was performed. Rh1 significantly suppressed IFN-γ-induced iNOS promoter activity by inhibiting DNA binding of several transcription factors, such as NF-jB, IRF-1, and STAT1. Furthermore, Rh1 inhibited the phosphorylation of JAK1, STAT1, STAT3, and ERK, which are upstream signaling molecules for IFNγ-induced iNOS gene expression. The present study demonstrates that Rh1 inhibits IFN-γ-induced JAK/ STAT and ERK signaling pathways and downstream transcription factors, and thereby iNOS gene expression. Therefore, the inhibition of microglial activation by ginsenoside Rh1 may provide potential therapeutic strategy for various neuroinflammatory diseases.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number2
DOIs
StatePublished - 25 Jun 2010

Keywords

  • Gene regulation
  • Ginsenoside Rh1
  • IFN-c
  • iNOS
  • Microglia
  • Signaling pathway

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