Induction of central signalling pathways and select functional effects in human platelets by beta-boswellic acid

Br J Pharmacol. 2005 Oct;146(4):514-24. doi: 10.1038/sj.bjp.0706366.


We have recently shown that in polymorphonuclear leukocytes, 11-keto boswellic acids (KBAs) induce Ca2+ mobilisation and activation of mitogen-activated protein kinases (MAPK). Here we addressed the effects of BAs on central signalling pathways in human platelets and on various platelet functions. We found that beta-BA (10 microM), the 11-methylene analogue of KBA, caused a pronounced mobilisation of Ca2+ from internal stores and induced the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)2, and Akt. These effects of beta-BA were concentration dependent, and the magnitude of the responses was comparable to those obtained after platelet stimulation with thrombin or collagen. Based on inhibitor studies, beta-BA triggers Ca2+ mobilisation via the phospholipase (PL)C/inositol-1,4,5-trisphosphate pathway, and involves Src family kinase signalling. Investigation of platelet functions revealed that beta-BA (> or =10 microM) strongly stimulates the platelet-induced generation of thrombin in an ex-vivo in-vitro model, the liberation of arachidonic acid (AA), and induces platelet aggregation in a Ca2+-dependent manner. In contrast to beta-BA, the 11-keto-BAs (KBA or AKBA) evoke only moderate Ca2+ mobilisation and activate p38 MAPK, but fail to induce phosphorylation of ERK2 or Akt, and do not cause aggregation or significant generation of thrombin. In summary, beta-BA potently induces Ca2+ mobilisation as well as the activation of pivotal protein kinases, and elicits functional platelet responses such as thrombin generation, liberation of AA, and aggregation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Arachidonic Acid / metabolism
  • Blood Platelets / drug effects*
  • Blood Platelets / physiology
  • Calcium Signaling / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • MAP Kinase Signaling System / drug effects*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Phosphorylation / drug effects
  • Platelet Aggregation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Thrombin / metabolism
  • Time Factors
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Type C Phospholipases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • src-Family Kinases / metabolism


  • Anti-Inflammatory Agents
  • Triterpenes
  • Arachidonic Acid
  • boswellic acid
  • src-Family Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • p38 Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Thrombin