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Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization
Anja Altmann1, Lutz Fischer, Manfred Schubert-Zsilavecz
1Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany.
Biochemical and Biophysical Research Communications
|January 10, 2002
Summary
Boswellia serrata extracts, specifically keto-boswellic acids (keto-BAs), activate key signaling pathways like mitogen-activated protein kinases (MAPK) in human immune cells. These compounds also mobilize calcium, suggesting a role in immune cell activation.
Area of Science:
- Immunology
- Pharmacology
- Natural Products Chemistry
Background:
- Boswellia serrata gum resins and their constituents, boswellic acids (BAs), are known for their potential therapeutic properties.
- The precise molecular mechanisms underlying the biological activities of BAs, particularly in immune cells, require further elucidation.
Purpose of the Study:
- To investigate the effect of Boswellia serrata extracts and specific boswellic acids on mitogen-activated protein kinases (MAPK) activation in human polymorphonuclear leukocytes (PMNL).
- To explore the role of intracellular calcium mobilization and key signaling pathways, such as phosphatidylinositol 3-kinase (PI 3-K) and protein kinase C (PKC), in BA-induced cellular responses.
Main Methods:
- Isolated human polymorphonuclear leukocytes (PMNL) were treated with Boswellia serrata extracts and purified boswellic acids.
- Mitogen-activated protein kinases (MAPK) activation (p42(MAPK) and p38) was measured.
- Intracellular free Ca(2+) mobilization was assessed.
- Inhibitor studies using PI 3-K and PKC inhibitors were conducted.
- The effect of calcium chelation on MAPK activation was evaluated.
Main Results:
- Boswellia serrata extracts and boswellic acids (BAs) rapidly and transiently activated p42(MAPK) and p38 in human PMNL in a dose-dependent manner.
- Keto-boswellic acids (keto-BAs), specifically 11-keto-beta-BA and 3-O-acetyl-11-beta-keto-BA, were more potent activators than other BAs.
- 11-keto-BAs induced rapid and significant mobilization of intracellular Ca(2+) in PMNL.
- Phosphatidylinositol 3-kinase (PI 3-K) was found to be involved in BA-induced MAPK activation, with a minor role for protein kinase C.
- MAPK activation by 3-O-acetyl-11-beta-keto-BA was partially dependent on extracellular Ca(2+).
Conclusions:
- 11-keto-boswellic acids are potent activators of human PMNL.
- The activation mechanism involves the stimulation of MAPK signaling pathways and the mobilization of intracellular Ca(2+).
- These findings provide molecular insights into the immunomodulatory effects of Boswellia serrata constituents.