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Lactucopicrin Inhibits Cytoplasmic Dynein‐Mediated NF‐κB Activation in Inflammated Macrophages and Alleviates Atherogenesis in Apolipoprotein E‐Deficient Mice
Author(s) -
He Luanying,
Weng Hui,
Li Qing,
Shi Guojun,
Liu Xiuping,
Du Yushi,
Zheng Jiakun,
Ling Wenhua,
Wang Dongliang
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000989
Subject(s) - macrophage , apolipoprotein b , nf κb , inflammation , nfkb1 , tumor necrosis factor alpha , proinflammatory cytokine , biology , microbiology and biotechnology , chemistry , endocrinology , immunology , transcription factor , biochemistry , cholesterol , in vitro , gene
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.