The new diterpene isodojaponin D inhibited LPS-induced microglial activation through NF-kappaB and MAPK signaling pathways

Ji Youn Lim, Tae Joon Won, Bang Yeon Hwang, Hak Rim Kim, Kwang Woo Hwang, Dong Geun Sul, So Young Park

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Neuroinflammation with prolonged microglial activation leads to increased levels of pro-inflammatory mediators and subsequently contributes to neuronal dysfunction and neuronal loss. Therefore, pharmacological suppression of neuroinflammation would theoretically slow the progression of neurodegenerative disease. In this study, we investigated the anti-inflammatory effects and possible mechanisms of isodojaponin D (19-hydroxy-1α,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide), a new diterpene isolated from Isodon japonicus against lipopolysaccharide(LPS)-induced microglial activation in BV2 cells. Results from RT-PCR and Western blot showed that pretreatment with isodojaponin D (5 and 10μg/ml) prior to treatment with LPS (1μg/ml) significantly decreased LPS-induced production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in a dose-dependent manner. In addition, LPS-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were also decreased by pretreatment with isodojaponin D. This effect was accompanied by a decrease in translocations of Nuclear Factor-KappaB (NF-κB) p50 and p65 from the cytoplasm to the nucleus and by a decrease in I kappaB (IκB) degradation. In addition, pretreatment with isodojaponin D significantly attenuated LPS-induced mitogen-activated protein kinase (MAPK) activation. Taken together, these results suggest that isodojaponin D suppressed LPS-induced microglial activation and production of pro-inflammatory mediators by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs. These results suggest that isodojaponin D could play a beneficial role in treatment of neurodegenerative disease.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalEuropean Journal of Pharmacology
Volume642
Issue number1-3
DOIs
Publication statusPublished - 2010 Sep 1

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Keywords

  • BV2 cells
  • COX-2
  • Cytokines
  • INOS
  • Isodojaponin D (19-hydroxy-1,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide)
  • Lipopolysaccharide
  • MAPKs
  • NF-κB

ASJC Scopus subject areas

  • Pharmacology

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