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Ellagic acid reduces high glucose‐induced endothelial dysfunction
Author(s) -
Rozentsvit Artur,
Samuel Sherin,
Gerdes Martin,
CarrilloSepulveda Maria Alicia
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1282.5
Subject(s) - myograph , endothelial dysfunction , ellagic acid , oxidative stress , vasodilation , chemistry , endocrinology , apoptosis , inflammation , medicine , endothelium , endothelial stem cell , pharmacology , stimulation , ec50 , antioxidant , biochemistry , in vitro , polyphenol
High‐glucose‐inducedvascular complications are a major problem among diabetic patients. Endothelial dysfunction is known to be an early event that underlies the development of subsequent vascular complications. Reduced vasodilation, a pro‐inflammatorystate, apoptosis, and oxidative stress are all linked to endothelial dysfunction. Recent studies have shown that ellagic acid (EA), a natural phenol found in numerous berries, has a cardio protective effect due to its anti‐inflammatory and anti‐oxidant properties. We hypothesize that EA attenuates high glucose‐induced endothelial dysfunction via its anti‐inflammatory and anti‐apoptotic effect. Wire myograph was utilized to measure acetylcholine(ACh)‐induced endothelium‐dependent relaxation. Isolated Sprague‐Dawley aortas treated for 24 hours with high glucose (HG, 30mM) exhibited decreased sensitivity (EC50) to ACh compared to control aortas (EC50 values: 6.25±0.04 vs. 6.71±0.07; p<0.05). Pre‐treatment with EA (20mM) significantly improved sensitivity to Ach (EC50 value: 6.54±0.02, p<0.001) in aortas exposed to HG. To test whether EA has an anti‐inflammatory and anti‐apoptotic vascular effect, in vitro studies were performed in human endothelial cell (EC)cultures. Prior to stimulation with HG for 24 hours, EC were pre‐treated with EA. HG increased COX‐2 protein expression (2.15±0.08 fold of increase vs. unstimulated cells), a marker of inflammation, which was reduced in the cell spre‐treated with EA. Moreover, DHE staining demonstrated that elevated ROS levels in EC treated with HG (3.2±0.2 fold of increase vs. unstimulated cells)were reduced (66% of reduction, p<0.001) in the presence of EA. Furthermore, HG increased Caspase‐3 levels (1.7±02 fold of increases vs. unstimulated cells, p<0.05) and enhanced DNA laddering in EC, both markers of apoptosis which were significantly reduced in the presence of EA. Together, these findings demonstrate that EA exerts an anti‐inflammatory and anti‐apoptotic effect on endothelial dysfunction, suggesting that EA may offer a potential vascular adjunct therapy for patients with diabetic vascular complications. 1EA attenuates high glucose‐induced endothelial dysfunction in aortas2Ellagic Acid decreases HG‐induced ROS generation in endothelial cells.