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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:272.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Antiinflammatory and Antiatherogenic Effects of the NF-B Inhibitor Acetyl-11-Keto-β-Boswellic Acid in LPS-Challenged ApoE^–/– Mice

Clarisse Cuaz-Pérolin; Ludivine Billiet; Eric Baugé; Corinne Copin; Daniel Scott-Algara; Felicitas Genze; Berhold Büchele; Tatiana Syrovets; Thomas Simmet; Mustapha Rouis

From Inserm, U-545 (C.Cuaz-Pérolin, L.B., E.B., C.Copin, M.R.), F-59019 Lille, France; Institut Pasteur de Lille (C.Cuaz-Pérolin, L.B., E.B., C.Copin, M.R.), Département d’Athérosclérose, F-59019 Lille, France; the Université de Lille 2 (C.Cuaz-Pérolin, L.B., E.B., C.Copin, 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.

Correspondence to Mustapha Rouis, INSERM UR545, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille, France. E-mail mustapha.rouis{at}pasteur-lille.fr

Abstract

Objective— In this article, we studied the effect of acetyl-11-keto-β-boswellic acid (AKβBA), 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 AKβBA 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 AKβBA. As a consequence, AKβBA 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, AKβBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKβBA 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 AKβBA-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. (Arterioscler Thromb Vasc Biol. 2008;28:272-277)

We studied the effect of acetyl-11-keto-β-boswellic acid (AKβBA), a natural antiinflammatory molecule isolated from the oleogum resin of Boswellia carterii, on LPS-induced atherosclerotic lesion in apoE^–/– mice. The results showed a significant reduction in the expression of several proatherogenic genes, NF-B activity, and lesion size in AKβBA-treated mice.

Key Words: boswellic acid • inflammation • cytokines • atherosclerosis • NF-B