Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses

J Immunol. 2009 Nov 1;183(9):5917-27. doi: 10.4049/jimmunol.0803336. Epub 2009 Oct 7.


Upon activation, microglia and astrocytes produce a number of proinflammatory molecules that participate in the pathophysiology of several neurodegenerative disorders. This study explores the anti-inflammatory property of cinnamon metabolite sodium benzoate (NaB) in microglia and astrocytes. NaB, but not sodium formate, was found to inhibit LPS-induced expression of inducible NO synthase (iNOS), proinflammatory cytokines (TNF-alpha and IL-1beta) and surface markers (CD11b, CD11c, and CD68) in mouse microglia. Similarly, NaB also inhibited fibrillar amyloid beta (Abeta)-, prion peptide-, double-stranded RNA (polyinosinic-polycytidylic acid)-, HIV-1 Tat-, 1-methyl-4-phenylpyridinium(+)-, IL-1beta-, and IL-12 p40(2)-induced microglial expression of iNOS. In addition to microglia, NaB also suppressed the expression of iNOS in mouse peritoneal macrophages and primary human astrocytes. Inhibition of NF-kappaB activation by NaB suggests that NaB exerts its anti-inflammatory effect through the inhibition of NF-kappaB. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on iNOS expression, and NF-kappaB activation by hydroxymethylglutaryl-CoA, mevalonate, and farnesyl pyrophosphate, but not cholesterol and ubiquinone, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the anti-inflammatory effect of NaB. Furthermore, we demonstrate that an inhibitor of p21(ras) farnesyl protein transferase suppressed the expression of iNOS, that activation of p21(ras) alone was sufficient to induce the expression of iNOS, and that NaB suppressed the activation of p21(ras) in microglia. These results highlight a novel anti-inflammatory role of NaB via modulation of the mevalonate pathway and p21(ras).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / enzymology
  • Astrocytes / pathology*
  • CHO Cells
  • Cells, Cultured
  • Cinnamomum zeylanicum / metabolism*
  • Cricetinae
  • Cricetulus
  • Cytokines / biosynthesis
  • Food Additives / metabolism
  • Food Additives / pharmacology*
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / pharmacology
  • Inflammation Mediators / physiology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mevalonic Acid / metabolism
  • Mice
  • Microglia / drug effects
  • Microglia / enzymology
  • Microglia / pathology*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / biosynthesis
  • Sodium Benzoate / metabolism
  • Sodium Benzoate / pharmacology*


  • Cytokines
  • Food Additives
  • Inflammation Mediators
  • Lipopolysaccharides
  • Nitric Oxide Synthase Type II
  • Sodium Benzoate
  • Mevalonic Acid