Inhibition of NF-κB activation and expression of inflammatory mediators by polyacetylene spiroketals from Plagius flosculosus

Transcription factor NF-kappa B plays a key role for the inducible expression of genes mediating proinflammatory effects and is thus an important target for the development of antiinflammatory drugs. Here, we show that extracts from the plant Plagius flosculosus (L.) Alavi and Heyw. can inhibit the induction of NF-kappa B activity, and we describe the identification of three spiroketal compounds. Of those, only compound I could inhibit the phosphorylation and proteasomal degradation of TKB, thus preventing the nuclear import and DNA binding of NF-kappa B. Accordingly, compound 1, which is also found in the widely used medicinal herb chamomile, interfered with the LPS-induced production of IL-1, IL-6, TNF, and PGE2 in primary human monocytes. (c) 2005 Elsevier B.V. All rights reserved.