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+).
Altmann
Anja
A
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany.
Fischer
Lutz
L
Schubert-Zsilavecz
Manfred
M
Steinhilber
Dieter
D
Werz
Oliver
O
D000328:Adult; D015153:Blotting, Western; D029743:Boswellia / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008956:Models, Chemical; D009504:Neutrophils / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D002614:Chelating Agents; D014315:Triterpenes; C054625:boswellic acid; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium