Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice

Audrey Chanet, Dragan Milenkovic, Christiane Deval, Mylène Potier, Joël Constans, Andrzej Mazur, Catherine Bennetau-Pelissero, Christine Morand, Annie M. Bérard
The Journal of Nutritional Biochemistry. 2012-05-01; 23(5): 469-477
DOI: 10.1016/j.jnutbio.2011.02.001

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1. J Nutr Biochem. 2012 May;23(5):469-77. doi: 10.1016/j.jnutbio.2011.02.001.
Epub 2011 Jun 17.

Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis
development in diet-induced hypercholesterolemia in mice.

Chanet A(1), Milenkovic D, Deval C, Potier M, Constans J, Mazur A,
Bennetau-Pelissero C, Morand C, Bérard AM.

Author information:
(1)INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.

Naringin (NAR) from grapefruit has exhibited potential protective effects
against atherosclerosis development. However, specific mechanisms responsible
for such effects are poorly understood. Thus, we aimed to investigate the
antiatherogenic effects of NAR in different mouse models of hypercholesterolemia
and decipher its molecular targets in the aorta using transcriptomic approach.
Two mouse models of hypercholesterolemia, wild-type mice fed a
high-fat/high-cholesterol diet and apolipoprotein E-deficient mice fed a
semisynthetic diet, were studied. Mice were fed a respective control diets
supplemented or not for 18 weeks with 0.02% of NAR, that is, nutritional
supplementation. NAR supplementation reduced plaque progression only in
wild-type mice fed the high-fat/high-cholesterol diet (-41%). Consistent with
this protective effect, NAR reduced plasma non-high-density lipoprotein
cholesterol concentrations as well as biomarkers of endothelial dysfunction.
Microarray studies performed on aortas demonstrated differentially expressed
genes encoding proteins involved in cell adhesion, actin cytoskeleton
organization and cell division. Thus, the changes in gene expression induced by
NAR could suggest a limited atherosclerosis progression by preventing immune
cell adhesion and infiltration in the intima of vascular wall, as well as smooth
muscle cell proliferation. Furthermore, this hypothesis was strengthened by in
vitro experiments, which showed the ability of naringenin to reduce monocyte
adhesion to endothelial cells and smooth muscle cell proliferation. In
conclusion, this study revealed the antiatherogenic effect of NAR supplemented
at a nutritionally achievable dose, specifically toward diet-induced
atherosclerosis, and depicted its multitarget mode of action at the vascular
level.