This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/2/272    most recent ATVBAHA.107.155606v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cuaz-Pérolin, C. Articles by Rouis, M. Search for Related Content PubMed PubMed Citation Articles by Cuaz-Pérolin, C. Articles by Rouis, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(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

This article has been cited by other articles:

				H. Wang, T. Syrovets, D. Kess, B. Buchele, H. Hainzl, O. Lunov, J. M. Weiss, K. Scharffetter-Kochanek, and T. Simmet Targeting NF-{kappa}B with a Natural Triterpenoid Alleviates Skin Inflammation in a Mouse Model of Psoriasis J. Immunol., October 1, 2009; 183(7): 4755 - 4763. [Abstract] [Full Text] [PDF]

				R. Largo, M. J. Martinez-Calatrava, O. Sanchez-Pernaute, M. E. Marcos, J. Moreno-Rubio, C. Aparicio, J. Egido, and G. Herrero-Beaumont Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H268 - H276. [Abstract] [Full Text] [PDF]

				A. B. Kunnumakkara, A. S. Nair, B. Sung, M. K. Pandey, and B. B. Aggarwal Boswellic Acid Blocks Signal Transducers and Activators of Transcription 3 Signaling, Proliferation, and Survival of Multiple Myeloma via the Protein Tyrosine Phosphatase SHP-1 Mol. Cancer Res., January 1, 2009; 7(1): 118 - 128. [Abstract] [Full Text] [PDF]

				J. Klein, J. Gonzalez, J. Duchene, L. Esposito, J. P. Pradere, E. Neau, C. Delage, D. Calise, A. Ahluwalia, P. Carayon, et al. Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy FASEB J, January 1, 2009; 23(1): 134 - 142. [Abstract] [Full Text] [PDF]