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

• Published in: Planta Medica
• Main Authors: Fakhrudin, N, Waltenberger, B, Cabaravdic, M, Atanasov, AG, Heiss, EH, Grzywacz, AM, Mihaly-Bison, J, Breuss, J, Rollinger, JM, Bochkov, V, Stuppner, H, Dirsch, V
• Format: Conference Proceeding
• Language: English
• Published: 21.08.2013
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-0033-1352060

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)