Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes

Br J Pharmacol. 2004 Jan;141(2):223-32. doi: 10.1038/sj.bjp.0705604. Epub 2003 Dec 22.


1. We have previously shown that 11-keto boswellic acids (11-keto-BAs), the active principles of Boswellia serrata gum resins, activate p38 MAPK and p42/44(MAPK) and stimulate Ca(2+) mobilisation in human polymorphonuclear leucocytes (PMNL). 2. In this study, we attempted to connect the activation of MAPK and mobilisation of Ca(2+) to functional responses of PMNL, including the formation of reactive oxygen species (ROS), release of arachidonic acid (AA), and leukotriene (LT) biosynthesis. 3. We found that, in PMNL, 11-keto-BAs stimulate the formation of ROS and cause release of AA as well as its transformation to LTs via 5-lipoxygenase. 4. Based on inhibitor studies, 11-keto-BA-induced ROS formation is Ca(2+)-dependent and is mediated by NADPH oxidase involving PI 3-K and p42/44(MAPK) signalling pathways. Also, the release of AA depends on Ca(2+) and p42/44(MAPK), whereas the pathways stimulating 5-LO are not readily apparent. 5. Pertussis toxin, which inactivates G(i/0) protein subunits, prevents MAPK activation and Ca(2+) mobilisation induced by 11-keto-BAs, implying the involvement of a G(i/0) protein in BA signalling. 6. Expanding studies on differentiated haematopoietic cell lines (HL60, Mono Mac 6, BL41-E-95-A) demonstrate that the ability of BAs to activate MAPK and to mobilise Ca(2+) may depend on the cell type or the differentiation status. 7. In summary, we conclude that BAs act via G(i/0) protein(s) stimulating signalling pathways that control functional leucocyte responses, in a similar way as chemoattractants, that is, N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor.

Publication types

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

MeSH terms

  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • HL-60 Cells
  • Humans
  • Leukocytes / drug effects*
  • Leukocytes / metabolism
  • Lipid Peroxides / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Reactive Oxygen Species / metabolism
  • Triterpenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases


  • Lipid Peroxides
  • Reactive Oxygen Species
  • Triterpenes
  • boswellic acid
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases