Antiinflammatory and Antiatherogenic Effects of the NF- B Inhibitor Acetyl-11-Keto- -Boswellic Acid in LPS-Challenged ApoE / Mice
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چکیده
Objective—In this article, we studied the effect of acetyl-11-keto-boswellic acid (AK BA), a natural inhibitor of the proinflammatory transcription factor NFB 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 AK BA significantly reduced it by 50%. Moreover, the activity of NFB was also reduced in the atherosclerotic plaques of LPS-injected apoE / mice treated with AK BA. As a consequence, AK BA treatment led to a significant downregulation of several NFB–dependent genes such as MCP-1, MCP-3, IL-1 , MIP-2, VEGF, and TF. By contrast, AK BA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocytederived cytokines. Moreover, AK BA potently inhibited the I B kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of I B and inhibition of p65/NFB activation. Comparable AK BA-mediated inhibition was also observed in LPS-stimulated human macrophages. Conclusion—The inhibition of NFB 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)
منابع مشابه
Acetyl-11-Keto- -Boswellic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing NF- B and NF- B-Regulated Gene Expression
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