Lactucopicrin Inhibits Cytoplasmic Dynein‐Mediated NF‐κB Activation in Inflammated Macrophages and Alleviates Atherogenesis in Apolipoprotein E‐Deficient Mice

Scope Nuclear factor-κB (NF-κB) activation in macrophages aggravates atherosclerosis. Dietary plant secondary metabolites including sesquiterpene lactone lactucopicrin target multiple organs. This study was focused on the impact of lactucopicrin on NF-κB activation in inflammated macrophages and atherogenesis in a mouse model of atherosclerosis. Methods and results In LPS-stimulated mouse bone marrow-derived macrophages, lactucopicrin inhibited NF-κB activation and concomitantly repressed the expression of IL-1β, IL-6 and tumor necrosis factor alpha. This effect was not due to modulation of inhibitor of NF-κB kinases (IKK) α/β/γ and NF-κB inhibitor α, and NF-κB/p65 DNA binding activity. Instead, the lactucopicrin effect was reliant on the inhibition of cytoplasmic dynein-mediated p65 transportation, a prerequisite step for p65 nuclear translocation. In high-fat diet-fed apolipoprotein E-deficient mice, lactucopicrin consumption dose-dependently reduced plaque area, inhibited plaque macrophage accumulation, attenuated plaque macrophage NF-κB activation, and reduced both plaque and serum inflammatory burden. However, lactucopicrin consumption did not affect the levels of serum lipids and anti-inflammatory cytokines (IL-4, IL-10 and transforming growth factor beta). Conclusion Dietary lactucopicrin inhibits atherogenesis in mice likely by its anti-inflammatory property. These findings suggest that dietary supplementation with lactucopicrin is a promising strategy to inhibit atherosclerotic cardiovascular disease. This article is protected by copyright. All rights reserved.