Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes

Biochim Biophys Acta. 2013 Apr;1830(4):2981-8. doi: 10.1016/j.bbagen.2013.01.018. Epub 2013 Jan 26.


Background: Chronic inflammation contributes to the development of pathological disorders including insulin resistance and atherosclerosis. Identification of anti-inflammatory natural products can prevent the inflammatory diseases.

Methods: Anti-inflammatory effects of blue-green algae (BGA), i.e., Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), were compared in RAW 264.7 and mouse bone marrow-derived macrophages (BMM) as well as splenocytes from apolipoprotein E knockout (apoE(-/-)) mice fed BGA.

Results: When macrophages pretreated with 100μg/ml NO lipid extract (NOE) or SP lipid extract (SPE) were activated by lipopolysaccharide (LPS), expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-6, were significantly repressed. NOE and SPE also significantly repressed the expression of TNFα and IL-1β in BMM. LPS-induced secretion of IL-6 was lower in splenocytes from apoE(-/-) fed an atherogenic diet containing 5% NO or SP for 12weeks. In RAW 264.7 macrophages, NOE and SPE markedly decreased nuclear translocation of NF-κB. The degree of repression of pro-inflammatory gene expression by algal extracts was much stronger than that of SN50, an inhibitor of NF-κB nuclear translocation. Trichostatin A, a pan histone deacetylase inhibitor, increased basal expression of IL-1β and attenuated the repression of the gene expression by SPE. SPE significantly down-regulated mRNA abundance of 11 HDAC isoforms, consequently increasing acetylated histone 3 levels.

Conclusion: NOE and SPE repress pro-inflammatory cytokine expression and secretion in macrophages and splenocytes via inhibition of NF-κB pathway. Histone acetylation state is likely involved in the inhibition.

General significance: This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cells, Cultured
  • Cyanobacteria / physiology*
  • Cytokines / biosynthesis*
  • Histone Deacetylases / physiology
  • Histones / metabolism
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / antagonists & inhibitors*
  • Spleen / cytology*


  • Cytokines
  • Histones
  • NF-kappa B
  • Histone Deacetylases