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Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2008 Feb; Vol. 28 (2), pp. 272-7. Date of Electronic Publication: 2007 Nov 21. - Publication Year :
- 2008
-
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.<br />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.<br />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.
- Subjects :
- Animals
Atherosclerosis genetics
Boswellia
Cells, Cultured
Disease Models, Animal
Inflammation drug therapy
Lipopolysaccharides administration & dosage
Lipopolysaccharides immunology
Mice
Mice, Knockout
Apolipoproteins E genetics
Atherosclerosis drug therapy
NF-kappa B antagonists & inhibitors
NF-kappa B drug effects
Plant Extracts pharmacology
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 28
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 18032778
- Full Text :
- https://doi.org/10.1161/ATVBAHA.107.155606