Circulating metabolites of strawberry mediate reductions in vascular inflammation and endothelial dysfunction in db/db mice

Abstract

Background: Cardiovascular disease is 2-4-fold more prevalent in patients with diabetes. Human studies support the cardiovascular benefits of strawberry consumption but the effects of strawberry on diabetic vasculature are unknown. We tested the hypothesis that dietary strawberry supplementation attenuates vascular inflammation and dysfunction in diabetic mice.Methods: Seven-week-old diabetic db/db mice that consumed standard diet (db/db) or diet supplemented with 235% freeze-dried strawberry (db/db + SB) for ten weeks were compared to non-diabetic control mice (db/+). Indices of vascular inflammation and dysfunction were measured. Endothelial cells (ECs) were isolated from the vasculature to determine the influence of strawberry on them. The effect of metabolites of strawberry on endothelial inflammation was determined by incubating mouse aortic ECs (MAECs) with +/- 5% serum, obtained from strawberry fed mice (metabolites serum) or standard diet fed mice (control serum) 25 mM glucose and 100 mu M palmitate.Results: db/db mice exhibited an increased monocyte binding to vessel, elevated blood pressure, and reduced endothelial-dependent vasorelaxation compared with db/+ mice but each defect was attenuated in db/db+ SB mice. The elevation of inflammatory molecules, NOX2 and inhibitor-kappa B kinase observed in ECs from db/db db/+ mice was suppressed in db/db + SB mice. Glucose and palmitate increased endothelial inflammation in MAECs but were normalized by co-incubation with metabolites serum.Conclusions: Dietary supplementation of strawberry attenuates indices of vascular inflammation and dysfunction in diabetic db/db mice. The effect of strawberry on vasculature is endothelial-dependent and possibly mediated through their circulating metabolites. Strawberry might complement conventional therapies to improve vascular complications in diabetics.,(C) 2018 Elsevier B.V. All rights reserved.