Clinical evidence of the vascular protective effects of grapefruit flavanones in post-menopausal women and potential molecular mechanisms involved
Résumé
Epidemiological studies reported that a high flavanone intake is associated with a reduced risk of
cardiovascular diseases (Mink et al, 2007; Cassidy et al, 2012), however clinical evidence is still
lacking. We carried out a cross-over RCT on 52 healthy post-menopausal women who have to
consumed daily and for 6-month, 340ml of grapefruit juice (providing 212mg naringenin-glycosides) or
of an iso-energetic control beverage mimicking the composition of the juice but without naringenin.
The aim of this trial was to evaluate the impact of GFJ consumption (i) on vascular function (blood
pressure, endothelial function and arterial stiffness) and (ii) on the gene and miRNA expression in
PBMCs isolated from enrolled volunteers using microarrays.
The intervention with GFJ improved pulse wave velocity (PWV), an indicator of arterial stiffness,
without affecting endothelial function (FMD) or blood pressure. The nutrigenomic study showed that
the regular intake of naringenin through GFJ consumption modulated the expression of genes and
miRNAs in PBMCs. Bioinformatic analysis of microarray data revealed that the differentially expressed
genes and the target genes of modulated miRNAs are involved in different cellular processes,
including inflammatory processes, chemotaxis, migration and cell adhesion, known to regulate
interactions between vascular endothelium and circulating immune cells. The observed changes in
genes and miRNAS expression profiles suggest a lower adhesion and infiltration of immune cells into
the vascular wall. This hypothesis is strengthened by results obtained from cell studies using
naringenin metabolites and showing their ability to reduce the adhesion of monocytes to activated
endothelial cells.
This study showed that a regular consumption of grapefruit juice by healthy postmenopausal women is
beneficial for central aortic stiffness and that this effect may be related to flavanones. The molecular
mechanisms showed as modulated by flavanones may be potentially involved in the beneficial effect
of grapefruit naringenin on vascular health in human.