Clinical evidence of the vascular protective effects of grapefruit flavanones in post-menopausal women and potential molecular mechanisms involved
Published on Nov 29, 2017
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.