Planta Med 2008; 74 - SL114
DOI: 10.1055/s-0028-1083994

The impact of sesquiterpene lactones on the expression of NF-κB1 and inflammatory genes controlled by NF-κB

S Gusenleitner 1, W Schuehly 1, A Schrammel 2, B Mayer 2, R Bauer 1
  • 1Institute of Pharmaceutical Sciences, Dept. of Pharmacognosy, University of Graz, Universitätsplatz 4/I, 8010 Graz, Austria
  • 2Institute of Pharmaceutical Sciences, Dept. of Pharmacology and Toxicology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria

Sesquiterpene lactones (SL) are secondary plant metabolites very widespread in the family of Asteraceae: helenalin from Arnica montana L. or parthenolide from Tanacetum parthenium L. Schultz-Bip. are just two examples.

Since the late 1990's the anti-inflammatory effect of such substances has been linked to a specific inhibition of nuclear factor kappa B (NF-κB) [1, 2]. This transcription factor plays a pivotal role in the regulation of immune response and inflammation, as it regulates the expression of many pro-inflammatory genes, like TNF-α, COX-2, IL-1β or IL-8 [3].

In a recent project we could provide molecular evidence, that SL, such as helenalin and parthenolide, target NF-κB by decreasing the mRNA levels as well as the protein expression of NF-κB1, thereby interrupting the classical NF-κB pathway. Furthermore also the mRNA levels of TNF-α and COX-2 were reduced. For structure-activity elucidation we determined the effect of 12 further SL on the mRNA expression level of NF-κB1. Among the tested substances, enhydrin, melcanthin C, helenin, arnicolid C and 11β, 13-Dihydrohelenalinisobutyrate caused a significant decrease in the NF-κB1 mRNA levels. While cinerenin, isohelenin, tenulin, tetraludin, isoaromaticin, 1β-Isoaromaticin and melcanthin B showed no significant effects. Due to these results it seems that not only SL featuring an exocyclic methylene moiety have the ability to reduce the expression of NF-κB1.

Acknowledgements: Olaf Kunert for NMR analysis.

References: 1. Bork, P. M. et al. (1997) FEBS Lett. 402: 85–90. 2. Lyss, G. et al. (1997) Biol. Chem. 378: 951–961. Karin, M. et al. (2004) Nat. Rev. Drug Discov. 3: 17–26.