TY - JOUR
T1 - Inhibition of NF-κB activation and expression of inflammatory mediators by polyacetylene spiroketals from Plagius flosculosus
AU - Calzado, Marco A.
AU - Lüdi, Katharina Schmid
AU - Fiebich, Bernd
AU - Ben-Neriah, Yinon
AU - Bacher, Susanne
AU - Munoz, Eduardo
AU - Ballero, Mauro
AU - Prosperini, Simona
AU - Appendino, Giovanni
AU - Schmitz, M. Lienhard
N1 - Funding Information:
This work was supported by a EU grant (AINP, contract QLK3-CT-2000-00463).
PY - 2005/6/30
Y1 - 2005/6/30
N2 - Transcription factor NF-κB 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-κB activity, and we describe the identification of three spiroketal compounds. Of those, only compound 1 could inhibit the phosphorylation and proteasomal degradation of IκB, thus preventing the nuclear import and DNA binding of NF-κB. 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.
AB - Transcription factor NF-κB 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-κB activity, and we describe the identification of three spiroketal compounds. Of those, only compound 1 could inhibit the phosphorylation and proteasomal degradation of IκB, thus preventing the nuclear import and DNA binding of NF-κB. 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.
KW - Cytokine
KW - Inducible transcription
KW - Inflammation
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=20444410744&partnerID=8YFLogxK
U2 - 10.1016/j.bbaexp.2005.04.007
DO - 10.1016/j.bbaexp.2005.04.007
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C2 - 15949852
AN - SCOPUS:20444410744
SN - 0167-4781
VL - 1729
SP - 88
EP - 93
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 2
ER -