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

Transcription factor NF-kappaB 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-kappaB activity, and we describe the identification of three spiroketal compounds. Of those, only compound 1 could inhibit the phosphorylation and proteasomal degradation of IkappaB, thus preventing the nuclear import and DNA binding of NF-kappaB. 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.