Elucidation of (−)-epicatechin metabolites after ingestion of chocolate by healthy humans

Actis‐Goretta, Lucas; Lévêques, Antoine; Giuffrida, Francesca; Romanov‐Michailidis, Fedor; Viton, Florian; Barron, Denís; Dueñas, Montserrat; González‐Manzano, Susana; Santos‐Buelga, Celestino; Williamson, Gary; Dionisi, Fabiola

doi:10.1016/j.freeradbiomed.2012.05.023

Cited by 117 publications

(141 citation statements)

References 37 publications

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“…The source temperature, capillary voltage, desolvation gas flow, and temperature were set up as described elsewhere (Actis-Goretta et al, 2012. It allowed us to detect and quantify the epicatechin metabolites following their m/z transitions with specific cone voltage and collision energy in multiple-reaction monitoring (MRM) Data Analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Several studies have shown that less than 30% of the (-)-epicatechin dose consumed is absorbed (Manach et al, 2005;Borges et al, 2010;Actis-Goretta et al, 2012. Following absorption in the intestinal tract, (-)-epicatechin is rapidly metabolized into glucuronide, sulfate, and/or methyl conjugates (Harada et al, 1999;Donovan et al, 2001;Actis-Goretta et al, 2012 (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we demonstrated that the plasma metabolic profile was different when (-)-epicatechin was consumed as chocolate or perfused as purified compound in the intestine (Actis-Goretta et al, 2012. Therefore, it could be suggested that other food ingredients modify the metabolism of (-)-epicatechin in vivo (Schramm et al, 2003;Neilson and Ferruzzi, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Sanchez-Bridge¹,

Lévêques²,

Li³

et al. 2014

Drug Metab Dispos

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Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (-)-epicatechin may reduce the risk of cardiovascular diseases. The interaction of (-)-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (-)-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 39-O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of (-)-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 39-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 39-Omethyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this (-)-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of (-)-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting (-)-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Sanchez-Bridge¹,

Lévêques²,

Li³

et al. 2014

Drug Metab Dispos

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“…Despite reported differences in analytical procedures between laboratories [47], the consensus is that (−)-epicatechin-3 -O-glucuronide, (−)-epicatechin-3 -O-sulfate, and a 3 -Omethyl-(−)-epicatechin-5/7-sulfate are the predominant epicatechin metabolites in humans after oral consumption [47,49]. The apparent half-life of most epicatechin conjugates is 2-4 h…”

Section: Absorption Into the Bloodstreammentioning

confidence: 99%

“…When hesperidin is consumed orally, hesperetin (conjugates of sulfate and glucuronide) appear in the plasma with a T max of 4-6 h. When hesperetin-7-Oglucoside is consumed orally, the same conjugates appear in the plasma but with a much higher C max and a much shorter T max of ~ 30 min indicating absorption in the small intestine (Fig. 4).Despite reported differences in analytical procedures between laboratories [47], the consensus is that (−)-epicatechin-3 -O-glucuronide, (−)-epicatechin-3 -O-sulfate, and a 3 -Omethyl-(−)-epicatechin-5/7-sulfate are the predominant epicatechin metabolites in humans after oral consumption [47,49]. The apparent half-life of most epicatechin conjugates is 2-4 h…”

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confidence: 99%

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

Williamson

Clifford

2017

Biochemical Pharmacology

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Please cite this article as: G. Williamson, M.N. Clifford, Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols, Biochemical Pharmacology (2017), doi: http://dx.doi.org/10.1016/ j. bcp.2017.03.012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1Role of the small intestine, colon and microbiota in determining the metabolic fate of in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged.Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites. and are also present at high levels in supplements [4], and form essential components of many Chinese medicines [5]. A study within the European Prospective Investigation intoCancer and Nutrition (EPIC) using the Phenol Explorer database reported that the cohort studied consumed 427 different polyphenols including 94 that were consumed at a rate of >1 g/day. The estimated total polyphenol consumption ranged from 584 mg/day by Greek women to 1786 mg/day for men in Aarhus-Denmark. The corresponding data for Greek men and for Aarhus women were 744 mg/day and 1626 mg/ day, respectively, with all data adjusted for age and weighted by season and weekday of dietary recall [6]. This study defined the major contributors to be the phenolic acids (predominantly the caffeoylquinic acids (27-53%), also called chlorogenic acids) and flavonoids (predominantly flavanols (16-29%), proanthocyanidins (5-9%) and theaflavins (14-25%)) [6]. Hydroxybenzoic acids (3.3-7.4%), alkyl-phenols (1.6...

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Profiling and identification of (−)‐epicatechin metabolites in rats using ultra‐high performance liquid chromatography coupled with linear trap‐Orbitrap mass spectrometer

Shang

Wang

Dai

et al. 2017

Drug Testing and Analysis

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(-)-Epicatechin (EC), an optical antipode of (+)-catechin (C), possesses many potential significant health benefits. However, the in vivo metabolic pathway of EC has not been clarified yet. In this study, an efficient strategy based on ultra-high performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer was developed to profile and characterize EC metabolites in rat urine, faeces, plasma, and various tissues. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filters (MMDFs), and diagnostic product ions (DPIs) were utilized to screen and identify EC metabolites from HR-ESI-MS to ESI-MS stage. Finally, a total of 67 metabolites (including parent drug) were tentatively identified based on standard substances, chromatographic retention times, accurate mass measurement, and relevant drug biotransformation knowledge. The results demonstrated that EC underwent multiple in vivo metabolic reactions including methylation, dehydration, hydrogenation, glucosylation, sulfonation, glucuronidation, ring-cleavage, and their composite reactions. Among them, methylation, dehydration, glucosylation, and their composite reactions were observed only occurring on EC when compared with C. Meanwhile, the distribution of these detected metabolites in various tissues including heart, liver, spleen, lung, kidney, and brain were respectively studied. The results demonstrated that liver and kidney were the most important organs for EC and its metabolites elimination. In conclusion, the newly discovered EC metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies. Copyright © 2017 John Wiley & Sons, Ltd.

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Elucidation of (−)-epicatechin metabolites after ingestion of chocolate by healthy humans

Cited by 117 publications

References 37 publications

Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Modulation of (–)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

Profiling and identification of (−)‐epicatechin metabolites in rats using ultra‐high performance liquid chromatography coupled with linear trap‐Orbitrap mass spectrometer

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