Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia

J Neurosci Res. 2007 Apr;85(5):1010-7. doi: 10.1002/jnr.21205.


Sustained microglial activation in the central nervous system (CNS) has been extensively investigated in age-related neurodegenerative diseases and has been postulated to lead to neuronal cell loss in these conditions. Recent studies have shown that antiinflammatory drugs may suppress microglial activation and thus protect against microglial overactivation and subsequent cell loss. Research also suggests that fruits such as berries may contain both antioxidant and antiinflammatory polyphenols that may be important in this regard. Our previous research showed that blueberry extract was effective in preventing oxidant-induced calcium response deficits in M1 (muscarinic receptor)-transfected COS-7 cells. Extrapolating from these findings, the current study investigated the effect of blueberry extract on preventing inflammation-induced activation of microglia. Results indicated that treatments with blueberry extract inhibited the production of the inflammatory mediator nitric oxide (NO) as well as the cytokines interleukin-1beta and tumor necrosis factor-alpha, in cell conditioned media from lipopolysaccharide (LPS)-activated BV2 microglia. Also, mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-activated BV2 cells were significantly reduced by treatments with blueberry extract. The results suggest that blueberry polyphenols attenuate inflammatory responses of brain microglia and could be potentially useful in modulation of inflammatory conditions in the CNS.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Blueberry Plants / chemistry
  • Cell Line
  • Culture Media, Conditioned / pharmacology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Encephalitis / drug therapy*
  • Encephalitis / immunology
  • Encephalitis / physiopathology
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Gliosis / drug therapy*
  • Gliosis / immunology
  • Gliosis / physiopathology
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Mice
  • Microglia / drug effects*
  • Microglia / immunology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Phenols / pharmacology*
  • Phenols / therapeutic use
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Polyphenols
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism


  • Antioxidants
  • Culture Media, Conditioned
  • Cytokines
  • Flavonoids
  • Inflammation Mediators
  • Lipopolysaccharides
  • Phenols
  • Plant Extracts
  • Polyphenols
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2