Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice.

Abstract

OBJECTIVE:

In this article, we studied the effect of acetyl-11-keto-beta-boswellic acid (AKbetaBA), a natural inhibitor of the proinflammatory transcription factor NF-kappaB on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/-) mice.

METHODS AND RESULTS:

Atherosclerotic lesions were induced by weekly LPS injection in apoE-/- mice. LPS alone increased atherosclerotic lesion size by approximately 100%, and treatment with AKbetaBA significantly reduced it by approximately 50%. Moreover, the activity of NF-kappaB was also reduced in the atherosclerotic plaques of LPS-injected apoE-/- mice treated with AKbetaBA. As a consequence, AKbetaBA treatment led to a significant downregulation of several NF-kappaB-dependent genes such as MCP-1, MCP-3, IL-1alpha, MIP-2, VEGF, and TF. By contrast, AKbetaBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKbetaBA potently inhibited the IkappaB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IkappaB alpha and inhibition of p65/NF-kappaB activation. Comparable AKbetaBA-mediated inhibition was also observed in LPS-stimulated human macrophages.

CONCLUSIONS:

The inhibition of NF-kappaB activity by plant resins from species of the Boswellia family might represent an alternative for classical medicine treatments for chronic inflammatory diseases such as atherosclerosis.

• Authors: Clarisse Cuaz-Pérolin, Ludivine Billiet, Eric Baugé, Corinne Copin, Daniel Scott-Algara, Felicitas Genze, Berhold Büchele, Tatiana Syrovets, Thomas Simmet, Mustapha Rouis
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 28 Issue 2 Pg. 272-7 (Feb 2008) ISSN: 1524-4636 [Electronic] United States
• PMID: 18032778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• Triterpenes
• acetyl-11-ketoboswellic acid

Topics

• Animals
• Apolipoproteins E (genetics)
• Atherosclerosis (drug therapy, genetics)
• Boswellia
• Cells, Cultured
• Disease Models, Animal
• Inflammation (drug therapy)
• Lipopolysaccharides (administration & dosage, immunology)
• Mice
• Mice, Knockout
• NF-kappa B (antagonists & inhibitors, drug effects)
• Plant Extracts (pharmacology)
• Triterpenes (pharmacology)