Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide- stimulated microglia: Critical role of the protein kinase A pathway and hemeoxygenase-1 expression

Ji Sun Jung, Jin A. Shin, Eun Mi Park, Jung Eun Lee, Young Sook Kang, Sung Won Min, Dong Hyun Kim, Jin Won Hyun, Chan Young Shin, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated microglia, while Rh1 increased anti-inflammatory IL-10 and hemeoxygenase-1 (HO-1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS-induced MAPK phosphorylation and nuclear factor-κB (NF-κB)-mediated transcription without affecting NF-κB DNA binding. As the increase of pCREB (cAMP responsive element-binding protein) is known to result in suppression of NF-κB-mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti-inflammatory effect of Rh1 because pre-treatment with protein kinase A inhibitors attenuated the Rh1-mediated inhibition of nitric oxide production and the up-regulation of IL-10 and HO-1. Furthermore, treatment of HO-1 shRNA attenuated Rh1-mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO-1, play a critical role in the anti-inflammatory mechanism of Rh1 by modulating pro- and anti-inflammatory molecules in activated microglia.

Original languageEnglish
Pages (from-to)1668-1680
Number of pages13
JournalJournal of Neurochemistry
Volume115
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • CREB
  • ginsenoside Rh1
  • HO-1
  • neuroinflammation
  • PKA

Fingerprint

Dive into the research topics of 'Anti-inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide- stimulated microglia: Critical role of the protein kinase A pathway and hemeoxygenase-1 expression'. Together they form a unique fingerprint.

Cite this