TY - JOUR 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 SP - 1657 LP - 1664 DO - 10.1124/mol.107.038810 VL - 72 IS - 6 AU - Arieh Moussaieff AU - Esther Shohami AU - Yoel Kashman AU - Ester Fride AU - M. Lienhard Schmitz AU - Florian Renner AU - Bernd L. Fiebich AU - Eduardo Munoz AU - Yinon Ben-Neriah AU - Raphael Mechoulam Y1 - 2007/12/01 UR - http://molpharm.aspetjournals.org/content/72/6/1657.abstract N2 - 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 ER -