| 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
(Affiliation: INSERM UR545, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille, France.)
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| Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 28
Issue 2
Pg. 272-7
(Feb 2008)
ISSN: 1524-4636 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)
|
