Effect of apple polyphenols on vascular oxidative stress and endothelium function: a translational study

• Published in: Molecular nutrition & food research Vol. 61; no. 11
• Main Authors: Cicero, Arrigo F.G., Caliceti, Cristiana, Fogacci, Federica, Giovannini, Marina, Calabria, Donato, Colletti, Alessandro, Veronesi, Maddalena, Roda, Aldo, Borghi, Claudio
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2017
• Subjects: Acid production; Allopurinol; Antioxidants - metabolism; Antioxidants - therapeutic use; Apple polyphenols; Apples; blood glucose; Blood Glucose - analysis; Body Mass Index; Body weight; Cells, Cultured; Clinical trials; Dietary Supplements; Double-Blind Method; Endothelial reactivity; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; enzyme activity; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - therapeutic use; Fasting plasma glucose; Female; Fruits; Human Umbilical Vein Endothelial Cells - cytology; Humans; Hyperuricemia - etiology; Hyperuricemia - prevention & control; in vitro studies; In vivo methods and tests; in vivo studies; inhibitory concentration 50; Male; Malus - chemistry; Overweight; Overweight - diet therapy; Overweight - metabolism; Overweight - pathology; Overweight - physiopathology; Oxidative Stress; patients; placebos; Plant Extracts - metabolism; Plant Extracts - therapeutic use; Polyphenols; Polyphenols - therapeutic use; Prediabetic State - etiology; Prediabetic State - prevention & control; Randomization; Serum uric acid; translation (genetics); Uric acid; Uric Acid - blood; Vascular Diseases - etiology; Vascular Diseases - prevention & control; Vascular Resistance; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism; Endothelial reactivity; Serum uric acid; Xanthine oxidase; Apple polyphenols; Fasting plasma glucose
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201700373

Scope We aimed examining apple polyphenols’ effect on uricemia and endothelial function in a sample of overweight subjects. Methods and results This was a two‐phased study. In vitro experiment aimed to evaluate apple polyphenols’ ability to lower uric acid in comparison with allopurinol. In vivo study consisted in a randomized, double‐blind, parallel placebo‐controlled clinical trial involving 62 overweight volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL), randomized to 300 mg apple polyphenols or placebo for 8 weeks. Apple polyphenols extract inhibited xanthine oxidase activity, with an IC50 = 130 ± 30 ng/mL; reducing uric acid production with an IC50 = 154 ± 28 ng/mL. During the trial, after the first 4 weeks of treatment, FPG decreased in the active treated group (−6.1%, p < 0.05), while no significant changes were observed regarding the other hematochemistry parameters. After 4 more weeks of treatment, active‐treated patients had an improvement in FPG compared to baseline (−10.3%, p < 0,001) and the placebo group (p < 0,001). Uric acid (−14.0%, p < 0.05 versus baseline; p < 0.05 versus placebo) and endothelial reactivity (0.24±0.09, p = 0.009 versus baseline; p < 0.05 versus placebo) significantly improved too. Conclusion In vivo, apple polyphenols extract has a positive effect on vascular oxidative stress and endothelium function and reduce FPG and uric acid by inhibiting xanthine oxidase, as our In vitro experiment attests. Apple's polyphenols including phloridzin, chlorogenic acid and quercetin work synergistically to modulate the glucose absorption, lower postprandial glycaemic load and regulate insulinaemic levels. Moreover, they have just been tested as uric acid lowering agents and seem to have vasorelaxant properties, even for low doses. Our in vivo findings reflect the in vitro ones, opening up new possibilities as adjunct therapy in lifestyle interventions to treat patients with both mild hyperuricemia and hyperglycemia. If confirmed in larger clinical trials, our results support the use of apple polyphenols among the potentially useful nutraceuticals for the management of the metabolic syndrome.