Royal Jelly Constituents Increase the Expression of Extracellular Superoxide Dismutase through Histone Acetylation in Monocytic THP-1 Cells

J Nat Prod. 2016 Apr 22;79(4):1137-43. doi: 10.1021/acs.jnatprod.6b00037. Epub 2016 Apr 6.


Extracellular superoxide dismutase (EC-SOD) is one of the main SOD isozymes and plays an important role in the prevention of cardiovascular diseases by accelerating the dismutation reaction of superoxide. Royal jelly includes 10-hydroxy-2-decenoic acid (10H2DA, 2), which regulates the expression of various types of genes in epigenetics through the effects of histone deacetylase (HDAC) antagonism. The expression of EC-SOD was previously reported to be regulated epigenetically through histone acetylation in THP-1 cells. Therefore, we herein evaluated the effects of the royal jelly constituents 10-hydroxydecanoic acid (10HDA, 1), sebacic acid (SA, 3), and 4-hydroperoxy-2-decenoic acid ethyl ester (4-HPO-DAEE, 4), which is a derivative of 2, on the expression of EC-SOD in THP-1 cells. The treatment with 1 mM 1, 2, or 3 or 100 μM 4 increased EC-SOD expression and histone H3 and H4 acetylation levels. Moreover, the enrichment of acetylated histone H4 was observed in the proximal promoter region of EC-SOD and was caused by the partial promotion of ERK phosphorylation (only 4) and inhibition of HDAC activities, but not by the expression of HDACs. Overall, 4 exerted stronger effects than 1, 2, or 3 and has potential as a candidate or lead compound against atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Fatty Acids / chemistry*
  • Fatty Acids / pharmacology*
  • Fatty Acids, Monounsaturated / chemistry
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Ketones / chemistry
  • Molecular Structure
  • Monocytes / drug effects*
  • Superoxide Dismutase / metabolism*


  • 4-hydroxy-1-phenyl-1-octanone
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Ketones
  • 4-decenoic acid
  • 2-decenoic acid
  • 10-hydroxy-2-decenoic acid
  • Superoxide Dismutase
  • Histone Deacetylases
  • royal jelly