Potential mechanisms underlying cardiovascular protection by polyphenols: Role of the endothelium

Oak, Min–Ho; Auger, Cyril; Belcastro, Eugenia; Park, Sin‐Hee; Lee, Hyunho; Schini‐Kerth, Valérie B.

doi:10.1016/j.freeradbiomed.2018.03.018

Cited by 97 publications

(106 citation statements)

References 150 publications

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“…In this context, plant polyphenols are likely good candidates since several of these well‐known antioxidant compounds are now widely regarded as pharmacological agents that regulate target proteins and associated signalling pathways including in pancreatic beta cells (Dall'Asta et al, ; Goszcz, Duthie, Stewart, Leslie, & Megson, ; Oak et al, ; Saponara, Carosati, Mugnai, Sgaragli, & Fusi, ). The possibility of developing polyphenol‐based therapeutics is further supported by studies reporting that a number of polyphenols elicit therapeutic‐like effects at pharmacological micromolar concentrations in cells, tissues, and various animal models (Bai et al, ; Gu et al, ; Wright, ; Zhao et al, ).…”

Section: Introductionmentioning

confidence: 99%

The ellagitannin metabolite urolithin C is a glucose‐dependent regulator of insulin secretion through activation of L‐type calcium channels

Bayle

Neasta

Dall’Asta

et al. 2019

British J Pharmacology

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Background and Purpose The pharmacology of polyphenol metabolites on beta‐cell function is largely undetermined. We sought to identify polyphenol metabolites that enhance the insulin‐secreting function of beta‐cells and to explore the underlying mechanisms. Experimental Approach INS‐1 beta‐cells and rat isolated islets of Langerhans or perfused pancreas preparations were used for insulin secretion experiments. Molecular modelling, intracellular Ca2+ monitoring, and whole‐cell patch‐clamp recordings were used for mechanistic studies. Key Results Among a set of polyphenol metabolites, we found that exposure of INS‐1 beta‐cells to urolithins A and C enhanced glucose‐stimulated insulin secretion. We further characterized the activity of urolithin C and its pharmacological mechanism. Urolithin C glucose‐dependently enhanced insulin secretion in isolated islets of Langerhans and perfused pancreas preparations. In the latter, enhancement was reversible when glucose was lowered from a stimulating to a non‐stimulating concentration. Molecular modelling suggested that urolithin C could dock into the Cav1.2 L‐type Ca2+ channel. Calcium monitoring indicated that urolithin C had no effect on basal intracellular Ca2+ but enhanced depolarization‐induced increase in intracellular Ca2+ in INS‐1 cells and dispersed cells isolated from islets. Electrophysiology studies indicated that urolithin C dose‐dependently enhanced the L‐type Ca2+ current for levels of depolarization above threshold and shifted its voltage‐dependent activation towards more negative potentials in INS‐1 cells. Conclusion and Implications Urolithin C is a glucose‐dependent activator of insulin secretion acting by facilitating L‐type Ca2+ channel opening and Ca2+ influx into pancreatic beta‐cells. Our work paves the way for the design of polyphenol metabolite‐inspired compounds aimed at ameliorating beta‐cell function.

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Section: Introductionmentioning

confidence: 99%

The ellagitannin metabolite urolithin C is a glucose‐dependent regulator of insulin secretion through activation of L‐type calcium channels

Bayle

Neasta

Dall’Asta

et al. 2019

British J Pharmacology

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“…Several studies report improved endothelial function as a result of red wine and/ or grape juice consumption. 20,24,25 This improved endothelial function was primarily demonstrated through enhanced Notes: Values are mean ± SD. Wine to juice cross comparisons for each variable were not significantly different.…”

Section: Discussionmentioning

confidence: 99%

“…18 Most studies have been conducted with common varietals such as Cabernet Sauvignon or Merlot, and very few have investigated muscadine-based wines. 19 Although epidemiological evidence suggests that moderate consumption of red wine is associated with a decrease in CVD, 6,20,21 the comprehensive effects of red wine, specifically muscadine wine, on vascular changes such as AIx and cPWV have not been examined in connection with changes in body composition, blood lipid profiles, inflammatory state, and antioxidant capacity.…”

Section: Introductionmentioning

confidence: 99%

<p>Chronic and acute effects of red wine versus red muscadine grape juice on body composition, blood lipids, vascular performance, inflammation, and antioxidant capacity in overweight adults</p>

McAnulty¹,

Collier²,

Hübner³

et al. 2019

IJWR

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Purpose: Red wine may benefit health due to the presence of polyphenolic compounds. This research investigated effects of wine (W) versus grape juice (J) on body composition, blood lipids (cholesterol, HDL, LDL, and triglycerides [TG]), vascular responses (augmentation index [AIx] and central pulse wave velocity [cPWV]), inflammation (C-reactive protein [CRP]), and plasma antioxidant capacity (ferric-reducing ability of plasma [FRAP]) in sedentary individuals. Methods: In a randomized crossover design, 19 participants consumed 300 mL of W or J for two weeks and then acutely in the lab. Blood was drawn at baseline, post two weeks, and within 1 hr after consuming treatment. Repeated measures ANOVA with 2 (treatment) × 3 (time) was used for FRAP, AIx, and cPWV and 2 (treatment) × 2 (time) for blood lipids and CRP. A paired t-test was used to compare differences in diet and weight change. Results: Acute, but not chronic, consumption of wine significantly increased FRAP (treatment P = 0.028) and significantly decreased AIx (treatment P = 0.038) while juice exhibited no effects. An overall treatment effect existed for TG (P = 0.028) in wine only. Cholesterol, LDL, HDL, and CRP were not affected in either group. Conclusion: Acute, but not chronic, consumption of wine significantly increased antioxidant capacity and resulted in beneficial changes to the vasculature as determined by AIx.

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“…Some of the most proposed protective mechanisms of action include the increase of antioxidant/detoxification enzymes activity (i.e., glutathione S-transferase, superoxide dismutase, glutathione peroxidase) [17][18][19], and the decrease of pro-inflammatory cytokines (i.e., tumor necrosis factor alpha (TNF-α), interleukin-1, interleukin-6) [20][21][22]. Furthermore, polyphenols have been documented to have the capability to modulate some factors involved in atherosclerosis, such as the release of numerous vasoconstrictor and vasodilator agents at the endothelial level including nitric oxide, endothelin-1 and soluble vascular cell adhesion molecules-1 (sVCAM-1) [23]. In this regard, we have previously reported the ability of different anthocyanins and metabolites to counteract and/or resolve an inflammation-driven adhesion of monocytes on endothelial cells (HUVECs).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis

et al. 2020

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The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion molecule (VCAM)-1, E-selectin and vascular endothelial growth factor (VEGF) in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL −1 ) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02 µM, 0.2 µM, 2 µM and 20 µM), VA and MetGA (0.05 µM, 0.5 µM, 5 µM and 50 µM) were tested. After 24 h, VCAM-1, E-selectin and VEGF were quantified by ELISA, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 µM to 20 µM) significantly (p < 0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (−37%, −24%, −30% and −47% for Peo-3-glc; −37%, −33%, −33% and −45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (−21%; p < 0.001). At the same concentrations, a significant (p < 0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p < 0.001) VEGF production. The present findings suggest that while Peo-3-glc and Pet-3-glc (but not their metabolites) reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites, suggesting a role in the regulation of angiogenesis.

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Potential mechanisms underlying cardiovascular protection by polyphenols: Role of the endothelium

Cited by 97 publications

References 150 publications

The ellagitannin metabolite urolithin C is a glucose‐dependent regulator of insulin secretion through activation of L‐type calcium channels

The ellagitannin metabolite urolithin C is a glucose‐dependent regulator of insulin secretion through activation of L‐type calcium channels

<p>Chronic and acute effects of red wine versus red muscadine grape juice on body composition, blood lipids, vascular performance, inflammation, and antioxidant capacity in overweight adults</p>

Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis

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