RT Journal Article
SR Electronic
T1 Incensole Acetate, a Novel Anti-Inflammatory Compound Isolated from <em>Boswellia</em> Resin, Inhibits Nuclear Factor-κB Activation
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1657
OP 1664
DO 10.1124/mol.107.038810
VO 72
IS 6
A1 Arieh Moussaieff
A1 Esther Shohami
A1 Yoel Kashman
A1 Ester Fride
A1 M. Lienhard Schmitz
A1 Florian Renner
A1 Bernd L. Fiebich
A1 Eduardo Munoz
A1 Yinon Ben-Neriah
A1 Raphael Mechoulam
YR 2007
UL http://molpharm.aspetjournals.org/content/72/6/1657.abstract
AB Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-κBα (IκBα) degradation in tumor necrosis factor (TNF) α-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-κB (NF-κB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IκB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-κB activation. It had no effect on IKK activity in vitro, and it did not suppress IκBα phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-κB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFα-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-κB inhibitors, originating from an ancient anti-inflammatory herbal remedy. The American Society for Pharmacology and Experimental Therapeutics