on November 21, 2007
Published online before print November 21, 2007, doi: 10.1161/ATVBAHA.107.155606
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Submitted on May 7, 2007
Accepted on November 8, 2007
Antiinflammatory and Antiatherogenic Effects of the NF-
B Inhibitor Acetyl-11-Keto-
-Boswellic Acid in LPS-Challenged ApoE-/- Mice
Clarisse Cuaz-Pérolin ;
From Inserm, U-545 (C.C.-P., L.B., E.B., C.C., M.R.), F-59019 Lille, France; Institut Pasteur de Lille (C.C.-P., L.B., E.B., C.C., M.R.), Département d’Athérosclérose, F-59019 Lille, France; the Université de Lille 2 (C.-C.-P., L.B., E.B., C.C., M.R.), Faculté de Pharmacie, F-59019 Lille, France; Unité de Régulation des Infections Rétrovirales (D.S.-A.), Institut Pasteur, F-75724 Paris, France; and Ulm University (F.G., B.B., T. Syrovets, T. Simmet), Institute of Pharmacology of Natural Products and Clinical Pharmacology, D-89081 Ulm, Germany.
* To whom correspondence should be addressed. E-mail: mustapha.rouis{at}pasteur-lille.fr.
Objective—In this article, we studied the effect of acetyl-11-keto-
-boswellic acid (AKBA), a natural inhibitor of the proinflammatory transcription factor NF-
B 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 
100%, and treatment with AKBA significantly reduced it by 50%. Moreover, the activity of NF-B was also reduced in the atherosclerotic plaques of LPS-injected apoE-/- mice treated with AKBA. As a consequence, AKBA treatment led to a significant downregulation of several NF-B–dependent genes such as MCP-1, MCP-3, IL-1
, MIP-2, VEGF, and TF. By contrast, AKBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKBA potently inhibited the IB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IB and inhibition of p65/NF-B activation. Comparable AKBA-mediated inhibition was also observed in LPS-stimulated human macrophages.
Conclusion—The inhibition of NF-B 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.
Key words: Boswellic acid • inflammation • cytokines • atherosclerosis • NF-
B
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