Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages

Min Hsiung Pan, Yen Hui Chang, Mei Ling Tsai, Ching Shu Lai, Sheng Yow Ho, Vladimir Badmaev, Chi Tang Ho

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Pterostilbene, an active constituent of blueberries, is known to possess anti-inflammatory activity and also to induce apoptosis in various types of cancer cells. Here, we investigated the inhibitory effects of pterostilbene on the induction of NO synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and real-time polymerase chain reaction (PCR) analyses demonstrated that pterostilbene significantly blocked the protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with pterostilbene resulted in the reduction of LPS-induced nuclear translocation of the nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB by blocking phosphorylation of inhibitor κB (IκB)α and p65 and subsequent degradation of IκBα. Transient transfection experiments using NFκB reporter constructs indicated that pterostilbene inhibits the transcriptional activity of NFκB in LPS-stimulated mouse macrophages. We found that pterostilbene also inhibited LPS-induced activation of PI3K/Akt, extracellular signal-regulated kinase 1/2 and p38 MAPK. Taken together, these results show that pterostilbene down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation of PI3K/Akt/IKK and MAPK. These results have an important implication for using pterostilbene toward the development of an effective anti-inflammatory agent.

Original languageEnglish (US)
Pages (from-to)7502-7509
Number of pages8
JournalJournal of agricultural and food chemistry
Volume56
Issue number16
DOIs
StatePublished - Aug 27 2008

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Cyclooxygenase-2 (COX-2)
  • Inducible NO synthesis (INOS)
  • Lipopolysaccharide (LPS)
  • Mitogen-activated protein (MAPK)
  • NFκB
  • Phosphatidylinositol 3-kinase (Pi3K)
  • Pterostilbene
  • RAW 264.7 monocyte/macrophages

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