Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages

Lipids. 2009 Sep;44(9):787-97. doi: 10.1007/s11745-009-3326-2. Epub 2009 Aug 5.

Abstract

Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / immunology
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / immunology
  • Cytokines / immunology
  • Dinoprostone / immunology
  • Gene Expression Regulation / drug effects
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Mice
  • Nitrogen Oxides / immunology
  • Tocotrienols / chemistry
  • Tocotrienols / pharmacology*
  • alpha-Tocopherol / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Nitrogen Oxides
  • Tocotrienols
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • alpha-Tocopherol
  • Dinoprostone