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