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

Abstract

Objective-In this article, we studied the effect of acetyl-11-keto-␤-boswellic acid (AK␤BA), a natural inhibitor of the proinflammatory transcription factor NF-B on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice. Methods and Results-Atherosclerotic lesions were induced by weekly LPS injection in apoE Ϫ/Ϫ mice. LPS alone increased atherosclerotic lesion size by Ϸ100%, and treatment with AK␤BA significantly reduced it by Ϸ50%. Moreover, the activity of NF-B was also reduced in the atherosclerotic plaques of LPS-injected apoE Ϫ/Ϫ mice treated with AK␤BA. As a consequence, AK␤BA 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, 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 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 AK␤BA-mediated inhibition was also observed in LPS-stimulated human macrophages. Conclusion-The

Targeting NF-κB with a Natural Triterpenoid Alleviates Skin Inflammation in a Mouse Model of Psoriasis

“…administration of AK␤BA, an inhibitor of IKK (18,19), inhibits NF-B activation in atherosclerotic lesions of apoE Ϫ/Ϫ mice (36). A single i.p.…”

A Novel Semisynthetic Inhibitor of the FRB Domain of Mammalian Target of Rapamycin Blocks Proliferation and Triggers Apoptosis in Chemoresistant Prostate Cancer Cells

“…Furthermore, the pentacyclic triterpenoid acetyl-11-keto-b-boswellic acid (AKbBA) was found to induce apoptosis in vitro and in vivo in human prostate cancer (Syrovets et al, 2005b), in colorectal cancer (Yadav et al, 2012), and in human pancreatic tumor xenografts (Park et al, 2011). AKbBA inhibits IkB kinase activity and subsequently nuclear factor-kB (NF-kB) both in vitro and in murine models in vivo (Syrovets et al, 2005a;Cuaz-Pérolin et al, 2008;Wang et al, 2009). Cinnamic acid is a plant-derived organic acid frequently used in flavors because of its special scent; natural derivatives of cinnamic acid may also exhibit antitumor properties (De et al, 2011).…”

Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE 2 .Ki Mice Fed a High-Fat Diet

“…27,28 On the basis of their structural diversity and biological activity, from a phytopharmaceutical point of view, specifically sesquiterpenes have been suggested to be of special interest among the terpenoids. 29 Sesquiterpene lactones can be categorized into 4 major classes: the germacranolides, eudesmanolides, guaianolides, and pseudoguaianolides.…”

“…Ki mice on an atherogenic diet 34 or exposed to lipopolysaccharide, an exacerbation of atherosclerosis is observed. 27 In the present study, we tested whether the natural NLRP3 inflammasome inhibitor arglabin, administered intraperitoneally, would affect the development of atherosclerosis in ApoE 2 .Ki mice fed a high-fat diet (HFD).…”