Skip to main content
Log in

Inhibitory Mechanism of 10-Hydroxy-trans-2-decenoic Acid (Royal Jelly Acid) Against Lipopolysaccharide- and Interferon-β-Induced Nitric Oxide Production

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Royal jelly acid, 10-hydroxy-trans-2-decenoic acid (10H2DA), is a major lipid component of royal jelly, which is the exclusive diet of queen honeybees. Previously, we showed partial inhibition of lipopolysaccharide (LPS)-induced NF-κB activation by 10H2DA. In this study, the ability of 10H2DA to inhibit LPS-induced nitric oxide (NO) production was investigated. LPS-induced NO production and inducible NO synthase (iNOS) gene transcription were inhibited by 10H2DA. LPS-stimulated interferon (IFN)-β production, IFN regulatory factor-1 induction and IFN-stimulated response element activation, which are required for iNOS induction, were unaffected by 10H2DA. IFN-β-induced NO production, however, was significantly inhibited by 10H2DA. Furthermore, IFN-β-induced nuclear factor (NF)-κB activation and tumour necrosis factor (TNF)-α production were significantly inhibited by 10H2DA, and TNF-α-induced NF-κB activation was also inhibited by 10H2DA. These results and our previous study suggest that 10H2DA inhibits LPS- and IFN-β-induced NO production via inhibition of NF-κB activation induced by LPS or IFN-β.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

REFERENCES

  1. Rembold, H. 1965. Biologically active substances in royal jelly. Vitamins and Hormones 23: 359–382.

    Article  PubMed  CAS  Google Scholar 

  2. Shuel, R., and S. Dixon. 1960. The early establishment of dimorphism in the female honeybee, Apis mellifera L. Insectes Sociaux 7: 265–282.

    Article  Google Scholar 

  3. Kohno, K., I. Okamoto, O. Sano, N. Arai, K. Iwaki, M. Ikeda, and M. Kurimoto. 2004. Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Bioscience, Biotechnology, and Biochemistry 68: 138–145.

    Article  PubMed  CAS  Google Scholar 

  4. Tamura, T., A. Fujii, and N. Kuboyama. 1987. Antitumor effects of royal jelly (RJ). Folia Pharmacologica Japonica 89: 73–80.

    Article  PubMed  CAS  Google Scholar 

  5. Helleu, C. 1956. Antibacterial properties of royal jelly; bactericidal and antibiotic effects of neutralized royal jelly. Annals of Institute Pasteur (Paris) 91: 231–237.

    CAS  Google Scholar 

  6. Lercker, G., P. Capella, L.S. Conte, F. Ruini, and G. Giordani. 1982. Components of royal jelly II. The lipid fraction, hydrocarbons and sterols. Journal of Apicultural Research 21: 178–184.

    CAS  Google Scholar 

  7. Townsend, G.F., J.F. Morgan, and B. Hazlett. 1959. Activity of 10-hydroxydecenoic acid from royal jelly against experimental leukaemia and ascitic tumours. Nature 183: 1270–1271.

    Article  PubMed  CAS  Google Scholar 

  8. Townsend, G.F., J.F. Morgan, S. Tolnai, B. Hazlett, H.J. Morton, and R.W. Shuel. 1960. Studies on the in vitro antitumor activity of fatty acids. I. 10-Hydroxy-2-decenoic acid from royal jelly. Cancer Research 20: 503–510.

    PubMed  CAS  Google Scholar 

  9. Blum, M.S., A.F. Novak, and S. Taber 3rd. 1959. 10-Hydroxy-δ 2-decenoic acid, an antibiotic found in royal jelly. Science 130: 452–453.

    Article  PubMed  CAS  Google Scholar 

  10. Sugiyama, T., K. Takahashi, S. Tokoro, T. Gotou, P. Neri, and H. Mori. 2011. Inhibitory effect of 10-hydroxy-trans-2-decenoic acid on LPS-induced IL-6 production via reducing IκB-ζ expression. Innate Immunity 18: 429–437.

    Article  PubMed  Google Scholar 

  11. Takahashi, K., T. Sugiyama, S. Tokoro, P. Neri, and H. Mori. 2012. Inhibition of interferon-γ-induced nitric oxide production by 10-hydroxy-trans-2-decenoic acid through inhibition of interferon regulatory factor-8 induction. Cellular Immunology 273: 73–78.

    Article  PubMed  CAS  Google Scholar 

  12. Vila-del Sol, V., M.D. Diaz-Munoz, and M. Fresno. 2007. Requirement of tumor necrosis factor α and nuclear factor-κB in the induction by IFN-γ of inducible nitric oxide synthase in macrophages. Journal of Leukocyte Biology 81: 272–283.

    Article  PubMed  CAS  Google Scholar 

  13. Xie, Q.W., R. Whisnant, and C. Nathan. 1993. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon γ and bacterial lipopolysaccharide. The Journal of Experimental Medicine 177: 1779–1784.

    Article  PubMed  CAS  Google Scholar 

  14. Kamijo, R., H. Harada, T. Matsuyama, M. Bosland, J. Gerecitano, D. Shapiro, J. Le, S.I. Koh, T. Kimura, S.J. Green, T.W. Mak, T. Taniguchi, and J. Vilcek. 1994. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263: 1612–1615.

    Article  PubMed  CAS  Google Scholar 

  15. Kim, Y.M., B.S. Lee, K.Y. Yi, and S.G. Paik. 1997. Upstream NF-κB site is required for the maximal expression of mouse inducible nitric oxide synthase gene in interferon-γ plus lipopolysaccharide-induced RAW 264.7 macrophages. Biochemical and Biophysical Research Communications 236: 655–660.

    Article  PubMed  CAS  Google Scholar 

  16. Martin, E., C. Nathan, and Q.W. Xie. 1994. Role of interferon regulatory factor 1 in induction of nitric oxide synthase. The Journal of Experimental Medicine 180: 977–984.

    Article  PubMed  CAS  Google Scholar 

  17. Ohmori, Y., and T.A. Hamilton. 2001. Requirement for STAT1 in LPS-induced gene expression in macrophages. Journal of Leukocyte Biology 69: 598–604.

    PubMed  CAS  Google Scholar 

  18. Sugiyama, T., T. Gotou, K. Moriyama, N. Kajiura, T. Hasegawa, J. Tomida, K. Takahashi, T. Komatsu, H. Ueda, K. Sato, S. Tokoro, P. Neri, and H. Mori. 2012. Mechanism of inhibition of lipopolysaccharide-induced interferon-β production by 2-aminopurine. Molecular Immunology 52: 299–304.

    Article  PubMed  CAS  Google Scholar 

  19. Sugiyama, T., M. Fujita, N. Koide, I. Mori, T. Yoshida, H. Mori, and T. Yokochi. 2004. 2-Aminopurine inhibits lipopolysaccharide-induced nitric oxide production by preventing IFN-β production. Microbiology and Immunology 48: 957–963.

    PubMed  CAS  Google Scholar 

  20. Green, L.C., D.A. Wagner, J. Glogowski, P.L. Skipper, J.S. Wishnok, and S.R. Tannenbaum. 1982. Analysis of nitrate, nitrite, and [15 N]nitrate in biological fluids. Analytical Biochemistry 126: 131–138.

    Article  PubMed  CAS  Google Scholar 

  21. McWhirter, S.M., K.A. Fitzgerald, J. Rosains, D.C. Rowe, D.T. Golenbock, and T. Maniatis. 2004. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proceedings of the National Academy of Sciences of the United States of America 101: 233–238.

    Article  PubMed  CAS  Google Scholar 

  22. Yang, C.H., A. Murti, S.R. Pfeffer, J.G. Kim, D.B. Donner, and L.M. Pfeffer. 2001. Interferon α/β promotes cell survival by activating nuclear factor κB through phosphatidylinositol 3-kinase and Akt. The Journal of Biological Chemistry 276: 13756–13761.

    PubMed  CAS  Google Scholar 

  23. Pahl, H.L. 1999. Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18: 6853–6866.

    Article  PubMed  CAS  Google Scholar 

  24. Schafer, S.L., R. Lin, P.A. Moore, J. Hiscott, and P.M. Pitha. 1998. Regulation of type I interferon gene expression by interferon regulatory factor-3. The Journal of Biological Chemistry 273: 2714–2720.

    Article  PubMed  CAS  Google Scholar 

  25. Yamamoto, M., S. Yamazaki, S. Uematsu, S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Kuwata, O. Takeuchi, K. Takeshige, T. Saitoh, S. Yamaoka, N. Yamamoto, S. Yamamoto, T. Muta, K. Takeda, and S. Akira. 2004. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. Nature 430: 218–222.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Japan Royal Jelly Fair Trade Council (Tokyo, Japan).

Conflict of Interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tsuyoshi Sugiyama.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 56 kb)

ESM 2

(PPT 2236 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugiyama, T., Takahashi, K., Kuzumaki, A. et al. Inhibitory Mechanism of 10-Hydroxy-trans-2-decenoic Acid (Royal Jelly Acid) Against Lipopolysaccharide- and Interferon-β-Induced Nitric Oxide Production. Inflammation 36, 372–378 (2013). https://doi.org/10.1007/s10753-012-9556-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-012-9556-0

KEY WORDS

Navigation