Phytoestrogenic Effects of Blackcurrant Anthocyanins Increased Endothelial Nitric Oxide Synthase (eNOS) Expression in Human Endothelial Cells and Ovariectomized Rats

Abstract

Phytoestrogens are plant-derived chemicals that are found in many foods and have estrogenic activity. We previously showed that blackcurrant extract (BCE) and anthocyanins have phytoestrogenic activity mediated via estrogen receptors (ERs), and anthocyanins may improve vascular function. BCE contains high levels of anthocyanins, but their health-promoting effects are unclear. This study examined the effects of BCE on the regulation of endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis in human endothelial cells as key regulators in cardiovascular disease. The results showed that eNOS mRNA levels were significantly upregulated in BCE- or anthocyanin-treated human vascular endothelial cells but decreased in cells treated with fulvestrant, an ER antagonist. These results corresponded with NO levels, suggesting that BCE and anthocyanin may regulate NO synthesis via eNOS expression. Thus, the phytoestrogenic effects exerted by BCE via ERs influenced eNOS mRNA expression and NO synthesis. In vivo, we investigated whether anthocyanin-rich BCE upregulated eNOS protein expression in ovariectomized (OVX) rats, a widely used animal model of menopause. Our results showed that anthocyanin-rich BCE significantly upregulated eNOS mRNA levels and NO synthesis through phytoestrogenic activity and therefore promoted blood vessel health in OVX rats as a postmenopausal model.

Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies

“…Pretreatment of HUVECs with Cy3-glc reversed the deleterious effects of palmitic acid by restoring the eNOS expression and NO ● synthesis [132]. A recent study found that ACNs from blackcurrant extract acted through direct interaction with estrogen receptors, leading to upregulation of the eNOS protein and NO ● synthesis [143].…”

Bioactive Compounds and Their Effect on Blood Pressure—A Review

“…Together with the above-mentioned qualities, in vitro studies suggest potential vasodilating qualities through the enhancement of endothelial nitric oxide synthase and nitric oxide production [ 21 , 22 ]. Endothelial nitric oxide synthase (eNOS) is an enzyme found in vascular endothelial cells and plays a major role in the production of nitric oxide (NO), which causes vasorelaxation of adjacent smooth muscle cells.…”

Blackcurrant (Ribes nigrum L.) Extract Exerts Potential Vasculoprotective Effects in Ovariectomized Rats, Including Prevention of Elastin Degradation and Pathological Vascular Remodeling

“…This study was approved by the Animal Research Committee of Hirosaki University (permission number: G 18003) and was conducted in accordance with the guidelines for animal experimentation of Hirosaki University. Ovariectomy and sham surgery rat treatment methods were performed according to our previous study [ 17 ]. Briefly, 12-week-old, female, Sprague-Dawley rats were purchased from CLEA Japan, Inc. (Tokyo, Japan), divided into 3 groups, and fed a diet supplemented with and without 3% BCE (as indicated) for 3 months.…”

“…Matrix metalloproteinase ( Mmp )-9 and Mmp-12 mRNA expression levels were evaluated by RT-qPCR analysis, as previously described [ 17 ]. Briefly, flash-frozen sections of the abdominal aorta were ground using a homogenizer, and total RNA was extracted using the RNeasy Mini Kit (Qiagen, Hilden, Germany).…”

“…We had previously reported that blackcurrant anthocyanins have phytoestrogenic activity mediated via ERα [ 13 ] and ERβ [ 14 ]. Moreover, polyphenol-rich blackcurrant extract (BCE) has shown beneficial effects via phytoestrogenic activity, such as cosmetic improvement of the skin [ 15 ], alleviation of hair loss [ 16 ], improvement in vascular endothelium function [ 17 ], and alleviation of lipid metabolism abnormalities [ 18 ] in ovariectomized (OVX) rats.…”