Abstract
Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.
Highlights
Life expectancy has increased as a result of novel scientific and technological advances and a decline in poverty, which has facilitated a reduction of communicable diseases [1]
The human umbilical cord vein endothelial cells (HUVECs) originated from human umbilical cords that were collected from normal-term placenta and obtained from the Department of Obstetrics and Gynecology, Clinical Centre, University of Debrecen, Debrecen, Hungary
To investigate the combined effect of the hyperglycemic environment and anthocyanin-rich sour cherry extract, HUVECs were maintained at high glucose levels and treated with anthocyanin-rich sour cherry extract as indicated
Summary
Life expectancy has increased as a result of novel scientific and technological advances and a decline in poverty, which has facilitated a reduction of communicable diseases [1]. This has shifted the attention of the medical community to treatment of noncommunicable, or chronic, conditions, such as diabetes mellitus (DM). In type 1 diabetes (T1D), the cause is an absolute deficiency of insulin secretion due to an autoimmune-mediated response. Type 2 diabetes (T2D), which is much more prevalent in the elderly, is caused by a combination of resistance to insulin action and insufficient compensatory insulin secretory response [3]. The microvascular endothelium is thought to be a major target of hyperglycemic damage as endothelial cells take up glucose passively in an insulin-independent manner and cannot downregulate the glucose transport rate when glucose concentration is elevated, resulting in intracellular hyperglycemia, which significantly affects endothelial cell biology [5]
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