Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by garcinol

Chiung Ho Liao, Shengmin Sang, Yu Chih Liang, Chi Tang Ho, Jen Kun Lin

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica fruit rind and other species. Recent studies have demonstrated that garcinol exhibited antioxidative effects in vitro. In this study, we found that garcinol inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated macrophages. Western blot analyzes and gel-shift assays revealed that garcinol strongly blocks the activation of eukaryotic transcription factor nuclear factor-kappa B (NF-κB)-induced by LPS. Moreover, transient transfection experiments showed that garcinol inhibited the NF-κB-dependent transcriptional activity. Based on these data, we demonstrated that inhibition of LPS-induced NF-κB activation occurred through suppressing the phosphorylation of IκBα and p38 mitogen-activated kinase (MAPK). Garcinol also lowers the LPS-induced increase of intracellular reactive oxygen species (ROS), which contributes to the activation of NF-κB. The NF-κB signaling pathway leads to inflammatory reaction and our results suggest that garcinol suppresses the expression of iNOS in this pathway.

Original languageEnglish
Pages (from-to)140-149
Number of pages10
JournalMolecular Carcinogenesis
Volume41
Issue number3
DOIs
Publication statusPublished - Nov 2004
Externally publishedYes

Keywords

  • COX-2
  • Garcinol
  • iNOS
  • NF-κB
  • p38 MAPK

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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