Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity in human platelets independent of Ca2+ and differentially interact with platelet-type 12-lipoxygenase

Mol Pharmacol. 2006 Sep;70(3):1071-8. doi: 10.1124/mol.106.024836. Epub 2006 Jun 20.


Boswellic acids inhibit the transformation of arachidonic acid to leukotrienes via 5-lipoxygenase but can also enhance the liberation of arachidonic acid in human leukocytes and platelets. Using human platelets, we explored the molecular mechanisms underlying the boswellic acid-induced release of arachidonic acid and the subsequent metabolism by platelet-type 12-li-poxygenase (p12-LO). Both beta-boswellic acid and 3-O-acetyl-11-keto-boswellic acid (AKBA) markedly enhanced the release of arachidonic acid via cytosolic phospholipase A2 (cPLA2), whereas for generation of 12-hydro(pero)xyeicosatetraenoic acid [12-H(P)ETE], AKBA was less potent than beta-boswellic acid and was without effect at higher concentrations (> or =30 microM). In contrast to thrombin, beta-boswellic acid-induced release of ara-chidonic acid and formation of 12-H(P)ETE was more rapid and occurred in the absence of Ca2+. The Ca2+-independent release of arachidonic acid and 12-H(P)ETE production elicited by beta-boswellic acid was not affected by pharmacological inhibitors of signaling molecules relevant for agonist-induced arachidonic acid liberation and metabolism. It is noteworthy that in cell-free assays, beta-boswellic acid increased p12-LO catalysis approximately 2-fold in the absence but not in the presence of Ca2+, whereas AKBA inhibited p12-LO activity. No direct modulatory effects of boswellic acids on cPLA2 activity in cell-free assays were evident. Therefore, immobilized KBA (linked to Sepharose beads) selectively precipitated p12-LO from platelet lysates but failed to bind cPLA2. Taken together, we show that boswellic acids induce the release of arachidonic acid and the synthesis of 12-H(P)ETE in human platelets by unique Ca2+-independent routes, and we identified p12-LO as a selective molecular target of boswellic acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 12-Lipoxygenase / metabolism*
  • Arachidonic Acid / metabolism*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology*
  • Blood Platelets / metabolism
  • Calcium / metabolism*
  • Cell-Free System
  • Humans
  • Kinetics
  • Leukotrienes / biosynthesis
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Signal Transduction / drug effects
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*


  • Leukotrienes
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Arachidonic Acid
  • boswellic acid
  • 12-HPETE
  • Arachidonate 12-Lipoxygenase
  • Phospholipases A
  • Phospholipases A2
  • Calcium