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.
Highlights
The risk of cardiovascular disease (CVD) generally increases with age but is lower in premenopausal women than in men of similar age; the risk increases markedly in women after menopause [1,2].This phenomenon is presumably in part due to estrogen deficiency in postmenopausal women, and the increased risk of CVD is associated with vascular endothelial dysfunction [2,3,4].Hormone-replacement therapy (HRT) containing estrogen is the most effective treatment for menopausal symptoms in healthy women
A preliminary experiment performed in our laboratory demonstrated that, in human umbilical vein endothelial cells (HUVECs), ERα expression was about 10 times higher than that of Erβ. These results suggest that the phytoestrogenic effects of blackcurrant extract (BCE) on HUVECs require ERα, which is consistent with a previous report [9,21]
We investigated whether BCE or anthocyanins stimulated Nitric oxide (NO) synthesis in EA.hy926 cells following five days of incubation in the presence or absence of fulvestrant for 24 h
Summary
The risk of cardiovascular disease (CVD) generally increases with age but is lower in premenopausal women than in men of similar age; the risk increases markedly in women after menopause [1,2].This phenomenon is presumably in part due to estrogen deficiency in postmenopausal women, and the increased risk of CVD is associated with vascular endothelial dysfunction [2,3,4].Hormone-replacement therapy (HRT) containing estrogen is the most effective treatment for menopausal symptoms in healthy women. The risk of cardiovascular disease (CVD) generally increases with age but is lower in premenopausal women than in men of similar age; the risk increases markedly in women after menopause [1,2]. This phenomenon is presumably in part due to estrogen deficiency in postmenopausal women, and the increased risk of CVD is associated with vascular endothelial dysfunction [2,3,4]. Hormone-replacement therapy (HRT) containing estrogen is the most effective treatment for menopausal symptoms in healthy women. Phytoestrogens are reported to Molecules 2019, 24, 1259; doi:10.3390/molecules24071259 www.mdpi.com/journal/molecules
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