PT  - JOURNAL ARTICLE
AU  - H Safayhi
AU  - E R Sailer
AU  - H P Ammon
TI  - Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid.
DP  - 1995 Jun 01
TA  - Molecular Pharmacology
PG  - 1212--1216
VI  - 47
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/47/6/1212.short
4100  - http://molpharm.aspetjournals.org/content/47/6/1212.full
SO  - Mol Pharmacol1995 Jun 01; 47
AB  - The formation of 5-lipoxygenase (EC 1.13.11.34) products from endogenous substrate by intact rat neutrophilic granulocytes and from exogenous arachidonic acid by rat granulocyte 105,000 x g supernatants and affinity chromatography-purified human leukocyte 5-lipoxygenase was inhibited by acetyl-11-keto-beta-boswellic acid (IC50 values of 1.5 microM, 8 microM, and 16 microM, respectively). With other pentacyclic triterpenes lacking the 11-keto function and/or the carboxyl function on ring A (e.g., amyrin and ursolic acid), no 5-lipoxygenase inhibition was observed. The presence of the noninhibitory pentacyclic triterpenes both in intact cells and in the cell-free system caused a concentration-dependent reversal of the 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid, whereas the inhibitory actions of 5-lipoxygenase inhibitors from different chemical classes (MK-886, L-739,010, ZM-230,487, and nordihydroguaiaretic acid) were not modified. The inhibition by acetyl-11-keto-beta-boswellic acid and the antagonism by noninhibitory pentacyclic triterpenes were not due to nonspecific lipophilic interactions, because lipophilic four-ring compounds (cholesterol, cortisone, and testosterone) neither inhibited the activity of the 5-lipoxygenase nor antagonized the inhibitory action of acetyl-11-keto-beta-boswellic acid. Therefore, we conclude that acetyl-11-keto-beta-boswellic acid acts directly on the 5-lipoxygenase enzyme at a selective site for pentacyclic triterpenes that is different from the arachidonate substrate binding site.