Evaluation of effects of cassis (Ribes nigrum L.) juice on human vascular function and gene expression using a microarray system

Abstract

Objective: Vascular function testing and microarray analysis were performed to evaluate the physical effects of cassis (Ribes nigrum L.) juice in women. Methods: In healthy women (Study I: n=21, age 53.6±3.6 years, BMI 24.2±3.9; Study II: n=40, age 47.4±8.8 years, BMI 22.4±3.9) assigned to one of four cassis groups (polysaccharide (PS) content: 0, 50, 125, and 250 mg) or a water control group (duration of intake: 2 to 8 weeks), the following parameters were assessed: for vascular function, blood pressure, thermographically measured body surface temperature, CAVI (cardio-ankle vascular index), ABI (ankle-brachial pressure index), accelerated plethysmography, and FMD (flow-mediated dilation) were determined. In the PS 250 mg (n=3) and water (n=4) groups, total RNA was extracted from blood collected before and 2 weeks after the study to perform gene expression analysis using Human Whole Genome 4 44K kit (Agilent). Results: Cassis juice (PS content: 125 to 250 mg) (n=16) increased body fat percentage (+2.5%, p=0.011), decreased systolic (121.3±15.8 mmHg at baseline,-4.8%, p=0.001) and diastolic blood pressure (76.9±11.2 mmHg at baseline,-5.9%, p=0.001), and increased FMD blood flow (p=0.004), upper limb temperature (+0.23±0.47˚C, p=0.011), and lower limb temperature (+0.55±0.50˚C, p<0.001). The percentage increase in lower limb temperature was dependent on PS (p<0.05) and polyphenol (p<0.01) contents. In gene analysis, inhibition of expression of α-adrenoceptor ADRA1D and thromboxane A2 receptor TBXA2R was prominent. Pathway analysis revealed significant accumulation of less frequently expressed genes (CACNA1B, GJB3, etc.) in the "Ca regulation in the cardiac cell" pathway (p=0.006). No serious adverse events occurred during the study. Conclusion: Cassis juice induced limb peripheral vasodilatation, increase in blood flow, and decrease in blood pressure. The microarray analysis showed inhibited expression of genes of α-adrenoceptor, thromboxane A2 receptor and Ca channel, and an inhibited pathway of Ca influx into vascular smooth muscle. Couppled with the fact that vascular endothelium plays a role in vasodilatation associated with various mRNA expressions, it is suggested that cassis juice may improve the function of endothelial cells.

The leaf extract of Ribes nigrum L. is a potent stimulator of the endothelial formation of NO in cultured endothelial cells and porcine coronary artery rings

“…Besides antioxidant and anti-inflammatory properties [13,14], Edirisinghe and colleagues [15] have shown that a blackcurrant juice concentrate is able to activate eNOS via the PI-3-kinase/Akt pathway in endothelial cells. Moreover, several studies have shown that blackcurrant juices are able to cause endothelium-dependent relaxations in rat aorta rings by increasing NO formation, in part, via the activation of histamine H 1 -receptors in endothelial cells [16][17][18]. The ability of blackcurrant products to activate the endothelial NO formation could be linked to their high level of anthocyanidins [19].…”

An Optimized Method for Analysis of Phenolic Compounds in Buds, Leaves, and Fruits of Black Currant (Ribes nigrum L.)

“…Using different in vitro and animal models, phenolic extracts of black currant fruit have been reported to exhibit, for example, antioxidant, anti-inflammatory, vasomodulatory, antihemostatic, and muscle relaxing effects, improvement of visual function, as well as neuroprotective and anticancer activities. − In humans, it has been shown that intake of anthocyanins improved shoulder stiffness due to typing work by increasing peripheral blood flow and reducing muscle fatigue . In addition, oral intake of black currant juice in healthy women has induced peripheral vasodilatation and led to increase in blood flow and decrease in blood pressure …”

“…11 In addition, oral intake of black currant juice in healthy women has induced peripheral vasodilatation and led to increase in blood flow and decrease in blood pressure. 12 The phenolic profile of black currant fruit has therefore been extensively studied during recent years, and several papers have been published on the use of HPLC-DAD-ESI-MS n for identification and quantification of phenolic compounds. 13−21 The profile includes a range of compounds, particularly phenolic acids (both hydroxybenzoic and hydroxycinnamic acids), flavonoids, and tannins.…”