Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries

Rymenant, Evelien Van; Grootaert, Charlotte; Beerens, K.; Needs, Paul W.; Kroon, Paul A.; Kerimi, Asimina; Williamson, Gary; Garcı́a-Villalba, Rocío; González‐Sarrías, Antonio; Tomás-Barberán, Francisco A.; Camp, John Van; Voorde, Johan Van de

doi:10.1039/c7fo01273j

Cited by 21 publications

(13 citation statements)

References 39 publications

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“…This lack of anti‐inflammatory activity was consistent with previous data observed for other activities of Uro such as antiproliferative, vasorelaxant, and (or) estrogenic, suggesting that phase‐II conjugation of Uro dampens their biological activity in vivo and in vitro. [ 47–49 ] Although free Uro are hardly detected in the bloodstream, a recent in vivo study has shown deconjugation of Uro‐A glucuronide to Uro‐A in a systemic LPS‐induced inflammation rat model, suggesting presence of free Uro‐A in microenvironments subjected to inflammatory stimuli. [ 50 ] Nevertheless, the capacity of leukocytes to hydrolyze Uro has not been investigated, justifying future studies on the metabolism of Uro by human leukocytes.…”

Section: Discussionmentioning

confidence: 99%

“…This could be relevant in human subjects belonging to the UM‐A metabotype (80% Uro‐A and 20% Uro‐C), and UM‐B (50% IsoUro‐A, 20% Uro‐B, 20% Uro‐A, 10% Uro‐C) compared to UM‐0 (non‐producers of Uro). [ 18,48,49 ] To determine whether these metabotypes are relevant in IBD, carefully designed in vitro and in vivo studies are required.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of 5‐Lipoxygenase‐Derived Leukotrienes and Hemiketals as a Novel Anti‐Inflammatory Mechanism of Urolithins

Giménez‐Bastida

González‐Sarrías

Espı́n

et al. 2020

Molecular Nutrition Food Res

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Scope Urolithins (Uro), gut microbial metabolites derived from ellagic acid (EA), reach significant concentrations in the human colon. Uro‐A exerts anti‐inflammatory activity in animal models of inflammatory bowel diseases (IBDs). It is hypothesized that Uro can modulate the biosynthesis of leukocyte‐derived inflammatory eicosanoids from the 5‐lipoxygenase (5‐LOX), cyclooxygenase‐2 (COX‐2), and 5‐LOX/COX‐2 pathways, relevant in the onset and progression of IBDs, including 5‐hydroxyeicosatetraenoic acids (5‐HETEs), leukotriene‐B4 (LTB4), prostaglandin E2 (PGE2), and hemiketals (HKE2 and HKD2). Methods and results Leukocytes, obtained from six healthy donors, are stimulated with lipopolysaccharide and calcium ionophore A23187. Uro, at concentrations found in the human colon (1–15 µm), decrease eicosanoid biosynthesis and COX‐2 levels in the activated leukocytes. In contrast, EA and conjugated Uro (glucuronides and sulfates) are inactive. Uro‐A and isourolithin‐A reduce the formation of the 5‐LOX/COX‐2 products HKE2 and HKD2 through the COX‐2 pathway (down‐regulation of COX‐2 and PGE2), whereas Uro‐C reduces 5‐HETE and LTB4 via inhibition of 5‐LOX. Conclusions The results show that physiologically relevant colonic Uro target eicosanoid biosynthetic pathways. The effect on HKs and LTB4 formation is unprecedented and expands the knowledge on anti‐inflammatory mechanisms of Uro against IBDs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of 5‐Lipoxygenase‐Derived Leukotrienes and Hemiketals as a Novel Anti‐Inflammatory Mechanism of Urolithins

Giménez‐Bastida

González‐Sarrías

Espı́n

et al. 2020

Molecular Nutrition Food Res

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“…The polyphenolic metabolites 3′,4′,5′-trihydroxyphenyl)-γ-valerolactone and 5-(3′,5′-dihydroxyphenyl)-γ-valerolactone also displayed, in spontaneously hypertensive rats, the capacity to lower angiotensin-1 converting enzyme activity and blood pressure, both contributing to improving endothelial function and arterial elasticity [ 235 ]. Paradoxically, the flavan-3-ol metabolites 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone, 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and 5-(3′-methoxy, 4′-hydroxyphenyl)-γ-valerolactone did not improve vascular endothelial plasticity of freshly isolated mouse saphenous arteries [ 236 ]. The dissimilarity in data could partially be explained by the different models used, especially that isolated saphenous artery endothelium is less reactive than the vessels of the spontaneously hypertensive rat.…”

Section: Polyphenol Metabolitesmentioning

confidence: 99%

Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?

et al. 2020

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Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.

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“…The tested compounds were purchased from Sigma Aldrich, syringic acid was purchased from Alfa Aesar, and phloroglucinol was purchased from Across Organics. PCA conjugates and gallic acid conjugates were synthesized in-house [40]. After treatment, the luciferase activity was measured as a marker of PON1 promoter activity.…”

Section: Treatmentsmentioning

confidence: 99%

The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function

et al. 2019

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High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.

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Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries

Cited by 21 publications

References 39 publications

Inhibition of 5‐Lipoxygenase‐Derived Leukotrienes and Hemiketals as a Novel Anti‐Inflammatory Mechanism of Urolithins

Inhibition of 5‐Lipoxygenase‐Derived Leukotrienes and Hemiketals as a Novel Anti‐Inflammatory Mechanism of Urolithins

Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?

The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function

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