Incensole Acetate, [...] Isolated from Boswellia Resin, Inhibits Nuclear Factor (NF)-kappa B Activation.

Incensole Acetate, a Novel anti-inflammatory compound Isolated from Boswellia Resin, Inhibits Nuclear Factor (NF)-kappa B Activation.: Mol Pharmacol. 2007 Sep 25; Authors: Moussaieff A, Shohami E, Kashman Y, Fride E, Schmitz ML, Renner F, Fiebich BL, Munoz E, Ben-Neriah Y, Mechoulam R

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 IkappaBalpha degradation in TNFalpha-stimulated HeLa cells as a read-out for a bioassay-guided fractionation. We thus isolated two novel NF-kappaB inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its non-acetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and LPS mediated NF-kappaB activation. It had no effect on IKK activity in vitro, nor did it suppress IkappaBalpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct, nor is it affecting all NF-kappaB activation pathways. The inhibitory effect appears specific as IA did not interfere with TNFalpha-induced activation of JNK and p38 MAPK. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, and specifically IA and its derivatives may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

PMID: 17895408 [PubMed - as supplied by publisher]