Planta Med 2013; 79 - PF3
DOI: 10.1055/s-0033-1352060

Discovery of Plumericin as a novel potent NF-κB inhibitor from Himatanthus sucuuba

N Fakhrudin 1, B Waltenberger 2, M Cabaravdic 3, AG Atanasov 4, EH Heiss 4, AM Grzywacz 4, J Mihaly-Bison 3, J Breuss 3, JM Rollinger 2, V Bochkov 3, H Stuppner 2, V Dirsch 4
  • 11. Department of Pharmacognosy, University of Vienna, Vienna 1090, Austria 2. Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
  • 2Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck 6020, Austria
  • 3Center for Physiology and Pharmacology, Institute for Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna 1090, Austria
  • 4Department of Pharmacognosy, University of Vienna, Vienna 1090, Austria

The transcription factor nuclear factor kappa B (NF-κB) plays a crucial role in the regulation of the inflammatory response and contributes to the development of various diseases (1). Thus, its inhibition is considered a promising approach to combat inflammation (2). In this study, we applied a bioactivity-guided approach to identify NF-κB inhibitors from the stem bark of Himatanthus sucuuba, an Amazonian plant traditionally used to treat inflammation-related disorders. We identified the spirolactone iridoid plumericin as a potent NF-κB inhibitor. Plumericin inhibits NF-κB activation in TNF-α stimulated HEK293 cells stably transfected with a NF-kB-driven luciferase reporter gene (293/NF-κB-luc cells), suppresses TNF-α-induced surface expression of adhesion molecules ICAM-1, VCAM-1 and E-selectin in endothelial cells, and reduces neutrophil recruitment in thioglycollate-induced peritonitis in mice. The effect of plumericin on the NF-κB signalling reveals to be a direct inhibition of the upstream kinase IKK-β. Consequently, it abolishes TNF-α-induced IκB phosphorylation and subsequent degradation. These findings might contribute to the development of promising anti-inflammatory leads and provide scientific evidence for the traditional use of Himatanthus sucuuba against inflammatory diseases.

References:

[1] Baker, R.G., Hayden, M.S., Ghosh, S., 2011, Cell Metabolism, 13(1): 11 – 22;

[2] Karin, M., Yamamoto, Y., and Wang, Q.M., 2004, Nature Review Drug Discovery 3: 17 – 26

Acknowledgements: This work was supported by the Austrian Federal Ministry for Science and Research and the Austrian Science Fund (Drugs from Nature Targeting Inflammation – DNTI project)