Antiinflammatory and antiatherogenic effects of the NF-κB inhibitor acetyl-11-keto-β-boswellic acid in LPS-challenged ApoE-/- mice

Objective-In this article, we studied the effect of acetyl-11-keto-beta-boswellic acid (AK beta BA), a natural inhibitor of the proinflammatory transcription factor NF-kappa 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 approximate to 100%, and treatment with AK beta BA significantly reduced it by approximate to 50%. Moreover, the activity of NF-kappa B was also reduced in the atherosclerotic plaques of LPS-injected apoE(-/-) mice treated with AK beta BA. As a consequence, AK beta BA treatment led to a significant downregulation of several NF-kappa B-dependent genes such as MCP-1, MCP-3, IL-1 alpha, MIP-2, VEGF, and TF. By contrast, AK beta BA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AK beta BA potently inhibited the I kappa B kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of I kappa B alpha and inhibition of p65/NF-kappa B activation. Comparable AK beta BA-mediated inhibition was also observed in LPS-stimulated human macrophages. Conclusion-The inhibition of NF-kappa 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.