Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization

Here we show that extracts of Boswellia serrata gum resins and its constituents, the boswellic acids (BAs), activate the mitogen-activated protein kinases (MAPK) p42(MAPK) and p38 in isolated human polymorphonuclear leukocytes (PMNL). MAPK activation was rapid and transient with maximal activation after 1-2.5 min of exposure and occurred in a dose-dependent manner. The keto-BAs (11-keto-beta-BA and 3-O-acetyl-11-beta-keto-BA) gave substantial kinase activation at 30 microM, whereas other BAs lacking the 11-keto group were less effective. Moreover, 11-keto-BAs induced rapid and prominent mobilization of free Ca(2+) in PMNL. Inhibitor studies revealed that phosphatidylinositol 3-kinase (PI 3-K) is involved in BA-induced MAPK activation, whereas a minor role was apparent for protein kinase C. MAPK activation by 3-O-acetyl-11-beta-keto-BA was partially inhibited when Ca(2+) was removed by chelation. Our results suggest that 11-keto-BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Ca(2+).