Bioassay-guided isolation of active anti-adipogenic compound from royal jelly and the study of possible mechanisms

BMC Complement Altern Med. 2019 Jan 29;19(1):33. doi: 10.1186/s12906-018-2423-2.

Abstract

Background: Royal jelly (RJ) has been used traditionally for dietary, cosmetic and health purposes for a long time in different parts of the world. Scientific studies have also shown its numerous health-promoting properties including hypoglycemic and anti-hypercholesterolemic action. In this study, we investigated the anti-adipogenic activity of RJ in 3 T3-L1 cells and isolated the major responsible root component for the activity.

Methods: An active anti-adipogenic compound was isolated through bioassay-guided isolation process by successive treatment of RJ and its active fractions on 3 T3-L1 cell line. (E)-10-Hydroxy-2-decenoic Acid (10-HDA) was identified using NMR spectroscopy and ultra-performance liquid chromatography (UPLC). As 10-HDA showed significant anti-adipogenic activity with Oil Red O staining and TG content assay on 3 T3-L1 adipocytes, further study was carried out in molecular level for the expression of adipogenic transcription factors such as PPARγ, FABP4, C/EBPα, SREBP-1c, and Leptin. The effect of 10-HDA on preliminary molecules such as pAkt, pERK, C/EBPβ, and pCREB were studied in the early stage of adipogenesis. The effect of 10-HDA on reactive oxygen species (ROS) production in fully differentiating adipocytes was measured by nitro blue tetrazolium (NBT) assay.

Result: Results showed that triacylglycerol accumulation and ROS production was markedly suppressed by 10-HDA. Preliminary molecules such as pAkt, pERK, pCERB, and C/EBPβ were found to be down-regulated by 10-HDA, which led to down-regulation of key adipogenic transcription factors such as PPARγ, FABP4, CEBPα, SREBP-1c, and Leptin on 3 T3-L1 adipocytes.

Conclusion: Our results suggest that anti-adipogenesis of 10-HDA on 3 T3-L1 adipocyte takes place via two mechanisms: inhibition of cAMP/PKA pathway and inhibition of p-Akt and MAPK dependent insulin signaling pathway. So it is considered that 10-HDA, a major component of RJ, can be a potential therapeutic medicine for obesity.

Keywords: (E)-10- Hydroxy-2-decenoic acid; 3 T3-L1 adipocyte; Insulin signaling pathway; Royal jelly; cAMP/PKA pathway.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects*
  • Animals
  • Biological Assay
  • Cell Survival / drug effects
  • Fatty Acids / chemistry*
  • Fatty Acids / pharmacology*
  • Fatty Acids, Monounsaturated / isolation & purification
  • Fatty Acids, Monounsaturated / pharmacology*
  • Insulin / metabolism
  • Lipid Metabolism / drug effects
  • Mice
  • Signal Transduction / drug effects

Substances

  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Insulin
  • 10-hydroxy-2-decenoic acid
  • royal jelly