Luanying He1, Hui Weng1, Qing Li1, Guojun Shi2, Xiuping Liu1, Yushi Du1, Jiakun Zheng1, Wenhua Ling1,3,4, Dongliang Wang1,3,4. 1. Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China. 2. Department of Endocrinology & Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China. 3. Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, P. R. China. 4. Guangdong Engineering Technology Research Center for Nutrition Translation, Guangzhou, P. R. China.
Abstract
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. This article is protected by copyright. All rights reserved.
SCOPE: Nuclear factor-κB (NF-κB) activation in macrophages aggravates atherosclerosis. Dietary plant secondary metabolites including sesquiterpene lactonelactucopicrin 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. This article is protected by copyright. All rights reserved.