Lactucopicrin Inhibits Cytoplasmic Dynein‐Mediated NF‐κB Activation in Inflammated Macrophages and Alleviates Atherogenesis in Apolipoprotein E‐Deficient Mice
Luanying He, Hui Weng, Qing Li, Guojun Shi, Xiuping Liu, Yushi Du, Jiakun Zheng, Wenhua Ling, Dongliang Wang
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 is focused on the impact of lactucopicrin on NF-κB activation in inflammed macrophages and atherogenesis in a mouse model of atherosclerosis. METHODS AND RESULTS: In LPS-stimulated mouse bone marrow-derived macrophages, lactucopicrin inhibits NF-κB activation, and concomitantly represses the expression of IL-1β, IL-6, and tumor necrosis factor-alpha. This effect is not due to modulation of the 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 is 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 reduces plaque area, inhibits plaque macrophage accumulation, attenuates plaque macrophage NF-κB activation, and reduces both plaque and serum inflammatory burden. However, lactucopicrin consumption does 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.