The Experts below are selected from a list of 22770 Experts worldwide ranked by ideXlab platform
Junji Terao - One of the best experts on this subject based on the ideXlab platform.
-
Inhibitory Effects of Conjugated Epicatechin Metabolites on Peroxynitrite-mediated Nitrotyrosine Formation.
Journal of Clinical Biochemistry and Nutrition, 2015Co-Authors: Midori Natsume, Naomi Osakabe, Akiko Yasuda, Toshihiko Osawa, Junji TeraoAbstract:Previously, we identified four metabolites of (−)-Epicatechin in blood and urine: (−)-Epicatechin-3'-O-glucuronide (E3'G), 4'-O-methyl-(−)-Epicatechin-3'-O-glucuronide (4'ME3'G), (−)-Epicatechin-7-O-glucuronide (E7G), and 3'-O-methyl-(−)-Epicatechin-7-O-glucuronide (3'ME7G) (Natsume et al. Free Radical Biol. Med. 34, 840-849, 2003). The aim of the current study was to compare the antioxidative activities of these metabolites with that of their parent compound. After oral administration of (−)-Epicatechin, E3'G and 4'ME3'G were isolated from human urine, and E7G and 3'ME7G isolated from rat urine. We found that these compounds inhibited peroxynitrite-mediated tyrosine nitration, in the following order of potency: E3'G > (−)-Epicatechin > E7G = 3'ME7G. = 4'ME3'G. These results demonstrate that the metabolites of (−)-Epicatechin retain antioxidative activity on peroxynitrite-induced oxidative damages to some extent.
-
structures of Epicatechin glucuronide identified from plasma and urine after oral ingestion of Epicatechin differences between human and rat
Free Radical Biology and Medicine, 2003Co-Authors: Midori Natsume, Seigo Baba, Naomi Osakabe, Toshihiko Osawa, Makoto Oyama, Motoko Sasaki, Yoshimasa Nakamura, Junji TeraoAbstract:Abstract (−)-Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels are found in black tea, apples, and chocolate. High intake of catechins has been associated with reduced risk of cardiovascular diseases. There have been several reports concerning the bioavailability of catechins, however, the chemical structure of (−)-Epicatechin metabolites in blood, tissues, and urine remains unclear. In the present study, we purified and elucidated the chemical structure of (−)-Epicatechin metabolites in human and rat urine after oral administration. Three metabolites were purified from human urine including (−)-Epicatechin-3′- O -glucuronide, 4′- O -methyl-(−)-Epicatechin-3′- O -glucuronide, and 4′- O -methyl-(−)-Epicatechin-5 or 7- O -glucuronide, according to 1 H- and 13 C-NMR, HMBC, and LC-MS analyses. The metabolites purified from rat urine were 3′- O -methyl-(−)-Epicatechin, (−)-Epicatechin-7- O -glucuronide, and 3′- O -methyl-(−)-Epicatechin-7- O -glucuronide. These compounds were also detected in the blood of humans and rats by LC-MS. The presence of these metabolites in blood and urine suggests that catechins are metabolized and circulated in the body after administration of catechin-containing foods.
-
Structures of (−)-Epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-Epicatechin: differences between human and rat
Free Radical Biology and Medicine, 2003Co-Authors: Midori Natsume, Seigo Baba, Naomi Osakabe, Toshihiko Osawa, Makoto Oyama, Motoko Sasaki, Yoshimasa Nakamura, Junji TeraoAbstract:Abstract (−)-Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels are found in black tea, apples, and chocolate. High intake of catechins has been associated with reduced risk of cardiovascular diseases. There have been several reports concerning the bioavailability of catechins, however, the chemical structure of (−)-Epicatechin metabolites in blood, tissues, and urine remains unclear. In the present study, we purified and elucidated the chemical structure of (−)-Epicatechin metabolites in human and rat urine after oral administration. Three metabolites were purified from human urine including (−)-Epicatechin-3′- O -glucuronide, 4′- O -methyl-(−)-Epicatechin-3′- O -glucuronide, and 4′- O -methyl-(−)-Epicatechin-5 or 7- O -glucuronide, according to 1 H- and 13 C-NMR, HMBC, and LC-MS analyses. The metabolites purified from rat urine were 3′- O -methyl-(−)-Epicatechin, (−)-Epicatechin-7- O -glucuronide, and 3′- O -methyl-(−)-Epicatechin-7- O -glucuronide. These compounds were also detected in the blood of humans and rats by LC-MS. The presence of these metabolites in blood and urine suggests that catechins are metabolized and circulated in the body after administration of catechin-containing foods.
-
absorption and urinary excretion of procyanidin b2 Epicatechin 4β 8 Epicatechin in rats
Free Radical Biology and Medicine, 2002Co-Authors: Seigo Baba, Naomi Osakabe, Midori Natsume, Junji TeraoAbstract:Abstract We evaluated the bioavailability and plasma antioxidative activity after administration of procyanidin B2 [Epicatechin-(4β-8)-Epicatechin] in rats. After procyanidin B2 administration, procyanidin B2 is absorbed and excreted in urine, and a portion of the PB2 is degraded to (−)-Epicatechin and to the metabolized conjugated and/or methylated (−)-Epicatechin internally in the rat. Moreover, PB2 reduces the accumulation of lipid peroxide in plasma oxidized by copper ions.
-
Absorption and urinary excretion of (-)-Epicatechin after administration of different levels of cocoa powder or (-)-Epicatechin in rats.
Journal of Agricultural and Food Chemistry, 2001Co-Authors: Seigo Baba, Naomi Osakabe, Midori Natsume, Yuko Muto, Toshio Takizawa, Junji TeraoAbstract:(−)-Epicatechin is a major polyphenol component of cocoa powder. The absorption and urinary excretion of (−)-Epicatechin following administration of different levels of either cocoa powder (150, 750, and 1500 mg/kg) or (−)-Epicatechin (1, 5, and 10 mg/kg) were evaluated in rats. Both the sum of plasma (−)-Epicatechin metabolites at 1 h postadministration and peak plasma concentrations increased in a dose-dependent fashion. The sum of (−)-Epicatechin metabolites in urine, excreted within 18 h postadministration, also increased with dose. Moreover, the sum of (−)-Epicatechin metabolites excreted in urine reached the same level in both (−)-Epicatechin and cocoa powder administration groups for equivalent amounts of (−)-Epicatechin. These results suggest that, in the dose range examined in this study, bioavailability of (−)-Epicatechin following administration of either (−)-Epicatechin or cocoa powder shows dose dependence and that the various compounds present in cocoa powder have little effect on the bioava...
Hagen Schroeter - One of the best experts on this subject based on the ideXlab platform.
-
Absorption, metabolism, distribution and excretion of (−)-Epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Javier I Ottaviani, Hagen Schroeter, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-Epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-Epicatechin. Studies have shown that [2-14C](–)-Epicatechin is absorbed in the small intestine with the 12 structural-related (–)-Epicatechin metabolites (SREMs), mainly in the form of (–)-Epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-Epicatechin-5-sulfate and (–)-Epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-Epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-Epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)hydracrylic acid, hippuric acid and 3′-hydroxyhippuric acid. Overall (–)-Epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-Epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-Epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-Epicatechin intake.
-
absorption metabolism distribution and excretion of Epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Javier I Ottaviani, Hagen Schroeter, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-Epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-Epicatechin. Studies have shown that [2-14C](–)-Epicatechin is absorbed in the small intestine with the 12 structural-related (–)-Epicatechin metabolites (SREMs), mainly in the form of (–)-Epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-Epicatechin-5-sulfate and (–)-Epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-Epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-Epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)hydracrylic acid, hippuric acid and 3′-hydroxyhippuric acid. Overall (–)-Epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-Epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-Epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-Epicatechin intake.
-
Enantioselective synthesis of orthogonally protected (2R,3R)-(−)-Epicatechin derivatives, key intermediates in the de novo chemical synthesis of (−)-Epicatechin glucuronides and sulfates
Tetrahedron-asymmetry, 2013Co-Authors: Mingbao Zhang, G. Erik Jagdmann, Michael C. Van Zandt, Paul Beckett, Hagen SchroeterAbstract:Abstract Ten orthogonally protected (−)-Epicatechin and 3′- or 4′- O -methyl-(−)-Epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (−)-Epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p -methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (−)-Epicatechin derivatives were designed to facilitate the regiospecific installation of a glucuronic acid or sulfate unit onto (−)-Epicatechin after selective removal of the MOM or PMB protecting group to provide authentic standards of (−)-Epicatechin glucuronides and sulfates.
-
Epicatechin stimulates erk dependent cyclic amp response element activity and up regulates glur2 in cortical neurons
Journal of Neurochemistry, 2007Co-Authors: Hagen Schroeter, Catherine Riceevans, Parmvir K Bahia, Jeremy P E Spencer, Olivia Sheppard, Marcus Rattray, Enrique Cadenas, Robert J WilliamsAbstract:Emerging evidence suggests that the cellular actions of flavonoids relate not simply to their antioxidant potential but also to the modulation of protein kinase signalling pathways. We investigated in primary cortical neurons, the ability of the flavan-3-ol, (-)Epicatechin, and its human metabolites at physiologically relevant concentrations, to stimulate phosphorylation of the transcription factor cAMP-response element binding protein (CREB), a regulator of neuronal viability and synaptic plasticity. (-)Epicatechin at 100–300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations, stimulation was no longer apparent and at the highest concentration tested (30 μmol/L) (-)Epicatechin was inhibitory. (-)Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. The human metabolite 3′-O-methyl-(-)Epicatechin was as effective as (-)Epicatechin at stimulating ERK phosphorylation, but (-)Epicatechin glucuronide was inactive. (-)Epicatechin and 3′-O-methyl-(-)Epicatechin treatments (100 nmol/L) increased CRE-luciferase activity in cortical neurons in a partially ERK-dependent manner, suggesting the potential to increase CREB-mediated gene expression. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)Epicatechin and this translated into an increase in GluR2 protein. Thus, (-)Epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
-
uptake and metabolism of Epicatechin and its access to the brain after oral ingestion
Free Radical Biology and Medicine, 2002Co-Authors: Manal Abd El M Mohsen, Gunter G C Kuhnle, A Rechner, Hagen Schroeter, Sarah Rose, Peter Jenner, Catherine RiceevansAbstract:Abstract Epicatechin is a flavan-3-ol that is commonly present in green teas, red wine, cocoa products, and many fruits, such as apples. There is considerable interest in the bioavailability of Epicatechin after oral ingestion. In vivo studies have shown that low levels of Epicatechin are absorbed and found in the circulation as glucuronides, methylated and sulfated forms. Recent research has demonstrated protective effects of Epicatechin and one of its in vivo metabolites, 3′-O-methyl Epicatechin, against neuronal cell death induced by oxidative stress. Thus, we are interested in the ability of ingested Epicatechin to cross the blood brain barrier and target the brain. Rats were administered 100 mg/kg body weight/d Epicatechin orally for 1, 5, and 10 d. Plasma and brain extracts were analyzed by HPLC with photodiode array detection and LC-MS/MS. This study reports the presence of the Epicatechin glucuronide and 3′-O-methyl Epicatechin glucuronide formed after oral ingestion in the rat brain tissue.
Catherine Riceevans - One of the best experts on this subject based on the ideXlab platform.
-
Epicatechin stimulates erk dependent cyclic amp response element activity and up regulates glur2 in cortical neurons
Journal of Neurochemistry, 2007Co-Authors: Hagen Schroeter, Catherine Riceevans, Parmvir K Bahia, Jeremy P E Spencer, Olivia Sheppard, Marcus Rattray, Enrique Cadenas, Robert J WilliamsAbstract:Emerging evidence suggests that the cellular actions of flavonoids relate not simply to their antioxidant potential but also to the modulation of protein kinase signalling pathways. We investigated in primary cortical neurons, the ability of the flavan-3-ol, (-)Epicatechin, and its human metabolites at physiologically relevant concentrations, to stimulate phosphorylation of the transcription factor cAMP-response element binding protein (CREB), a regulator of neuronal viability and synaptic plasticity. (-)Epicatechin at 100–300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations, stimulation was no longer apparent and at the highest concentration tested (30 μmol/L) (-)Epicatechin was inhibitory. (-)Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. The human metabolite 3′-O-methyl-(-)Epicatechin was as effective as (-)Epicatechin at stimulating ERK phosphorylation, but (-)Epicatechin glucuronide was inactive. (-)Epicatechin and 3′-O-methyl-(-)Epicatechin treatments (100 nmol/L) increased CRE-luciferase activity in cortical neurons in a partially ERK-dependent manner, suggesting the potential to increase CREB-mediated gene expression. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)Epicatechin and this translated into an increase in GluR2 protein. Thus, (-)Epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.
-
uptake and metabolism of Epicatechin and its access to the brain after oral ingestion
Free Radical Biology and Medicine, 2002Co-Authors: Manal Abd El M Mohsen, Gunter G C Kuhnle, A Rechner, Hagen Schroeter, Sarah Rose, Peter Jenner, Catherine RiceevansAbstract:Abstract Epicatechin is a flavan-3-ol that is commonly present in green teas, red wine, cocoa products, and many fruits, such as apples. There is considerable interest in the bioavailability of Epicatechin after oral ingestion. In vivo studies have shown that low levels of Epicatechin are absorbed and found in the circulation as glucuronides, methylated and sulfated forms. Recent research has demonstrated protective effects of Epicatechin and one of its in vivo metabolites, 3′-O-methyl Epicatechin, against neuronal cell death induced by oxidative stress. Thus, we are interested in the ability of ingested Epicatechin to cross the blood brain barrier and target the brain. Rats were administered 100 mg/kg body weight/d Epicatechin orally for 1, 5, and 10 d. Plasma and brain extracts were analyzed by HPLC with photodiode array detection and LC-MS/MS. This study reports the presence of the Epicatechin glucuronide and 3′-O-methyl Epicatechin glucuronide formed after oral ingestion in the rat brain tissue.
-
contrasting influences of glucuronidation and o methylation of Epicatechin on hydrogen peroxide induced cell death in neurons and fibroblasts
Free Radical Biology and Medicine, 2001Co-Authors: Jeremy P E Spencer, Gunter G C Kuhnle, Hagen Schroeter, Robert J Williams, Andrew J Crossthwaithe, Catherine RiceevansAbstract:The purpose of this study was to examine the comparative mechanisms by which the dietary form of the flavonoid Epicatechin and its predominant in vivo metabolite, Epicatechin glucuronide, influence oxidative stress-induced cell death in fibroblasts and neurons. The results demonstrate the contrasting influences of in vivo glucuronidation and methylation on the bioactivity of Epicatechin.
-
Epicatechin and its in vivo metabolite 3 o methyl Epicatechin protect human fibroblasts from oxidative stress induced cell death involving caspase 3 activation
Biochemical Journal, 2001Co-Authors: Jeremy P E Spencer, Gunter G C Kuhnle, Hagen Schroeter, S K S Srai, Rex M Tyrrell, Ulrich Hahn, Catherine RiceevansAbstract:There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, Epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of Epicatechin in vivo is 3'-O-methyl Epicatechin, we have compared its protective effects with that of Epicatechin. The results provide the first evidence that 3'-O-methyl Epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3'-O-methyl Epicatechin is not significantly different from that of Epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.
Javier I Ottaviani - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of Epicatechin metabolites as recovery biomarker of dietary flavan 3 ol intake
Scientific Reports, 2019Co-Authors: Javier I Ottaviani, Reedmond Fong, Jennifer Kimball, Jodi L Ensunsa, Nicola Gray, Anna Vogiatzoglou, Abigail Britten, Debora Lucarelli, Robert Luben, Philip B GraceAbstract:Data from dietary intervention studies suggest that intake of (−)-Epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (−)-Epicatechin metabolites (SREM), particularly (−)-Epicatechin-3′-glucuronide, (−)-Epicatechin- 3′-sulfate and 3′-o-methyl-(−)-Epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-Epicatechin intake. SReMB in urine proved to be a specific indicator of (−)-Epicatechin intake, showing also a strong correlation with the amount of (−)-Epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (−)-Epicatechin as SReMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 μmol/L. our results show that SReMB are suitable as biomarker of (−)-Epicatechin intake. According to evaluation criteria from iARc and the institute of Medicine, the results obtained support use of SReMB as a recovery biomarker to estimate actual intake of (−)-Epicatechin.
-
Evaluation of (-)-Epicatechin metabolites as recovery biomarker of dietary flavan-3-ol intake.
Scientific Reports, 2019Co-Authors: Javier I Ottaviani, Reedmond Fong, Jennifer Kimball, Jodi L Ensunsa, Nicola Gray, Anna Vogiatzoglou, Abigail Britten, Debora Lucarelli, Robert Luben, Philip B GraceAbstract:: Data from dietary intervention studies suggest that intake of (-)-Epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (-)-Epicatechin metabolites (SREM), particularly (-)-Epicatechin-3'-glucuronide, (-)-Epicatechin-3'-sulfate and 3'-O-methyl-(-)-Epicatechin-5-sulfate (SREMB), as flavan-3-ol and (-)-Epicatechin intake. SREMB in urine proved to be a specific indicator of (-)-Epicatechin intake, showing also a strong correlation with the amount of (-)-Epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (-)-Epicatechin as SREMB in 24 h urine was 10% (IQR 7-13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L. Our results show that SREMB are suitable as biomarker of (-)-Epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (-)-Epicatechin.
-
Absorption, metabolism, distribution and excretion of (−)-Epicatechin: A review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Javier I Ottaviani, Hagen Schroeter, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-Epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-Epicatechin. Studies have shown that [2-14C](–)-Epicatechin is absorbed in the small intestine with the 12 structural-related (–)-Epicatechin metabolites (SREMs), mainly in the form of (–)-Epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-Epicatechin-5-sulfate and (–)-Epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-Epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-Epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)hydracrylic acid, hippuric acid and 3′-hydroxyhippuric acid. Overall (–)-Epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-Epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-Epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-Epicatechin intake.
-
absorption metabolism distribution and excretion of Epicatechin a review of recent findings
Molecular Aspects of Medicine, 2017Co-Authors: Gina Borges, Javier I Ottaviani, Hagen Schroeter, Justin J J Van Der Hooft, Alan CrozierAbstract:Abstract This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (–)-Epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (–)-Epicatechin. Studies have shown that [2-14C](–)-Epicatechin is absorbed in the small intestine with the 12 structural-related (–)-Epicatechin metabolites (SREMs), mainly in the form of (–)-Epicatechin-3′-O-glucuronide, 3′-O-methyl-(–)-Epicatechin-5-sulfate and (–)-Epicatechin-3′-sulfate, attaining sub-μmol/L peak plasma concentrations (Cmax) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (–)-Epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)–γ-hydroxyvaleric acids which appear in plasma as phase II metabolites with a Cmax of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (–)-Epicatechin. Other catabolites excreted in 0–24 h urine in amounts equivalent to 28% of intake included 3-(3′-hydroxyphenyl)hydracrylic acid, hippuric acid and 3′-hydroxyhippuric acid. Overall (–)-Epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (–)-Epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (–)-Epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (–)-Epicatechin intake.
Seigo Baba - One of the best experts on this subject based on the ideXlab platform.
-
structures of Epicatechin glucuronide identified from plasma and urine after oral ingestion of Epicatechin differences between human and rat
Free Radical Biology and Medicine, 2003Co-Authors: Midori Natsume, Seigo Baba, Naomi Osakabe, Toshihiko Osawa, Makoto Oyama, Motoko Sasaki, Yoshimasa Nakamura, Junji TeraoAbstract:Abstract (−)-Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels are found in black tea, apples, and chocolate. High intake of catechins has been associated with reduced risk of cardiovascular diseases. There have been several reports concerning the bioavailability of catechins, however, the chemical structure of (−)-Epicatechin metabolites in blood, tissues, and urine remains unclear. In the present study, we purified and elucidated the chemical structure of (−)-Epicatechin metabolites in human and rat urine after oral administration. Three metabolites were purified from human urine including (−)-Epicatechin-3′- O -glucuronide, 4′- O -methyl-(−)-Epicatechin-3′- O -glucuronide, and 4′- O -methyl-(−)-Epicatechin-5 or 7- O -glucuronide, according to 1 H- and 13 C-NMR, HMBC, and LC-MS analyses. The metabolites purified from rat urine were 3′- O -methyl-(−)-Epicatechin, (−)-Epicatechin-7- O -glucuronide, and 3′- O -methyl-(−)-Epicatechin-7- O -glucuronide. These compounds were also detected in the blood of humans and rats by LC-MS. The presence of these metabolites in blood and urine suggests that catechins are metabolized and circulated in the body after administration of catechin-containing foods.
-
Structures of (−)-Epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-Epicatechin: differences between human and rat
Free Radical Biology and Medicine, 2003Co-Authors: Midori Natsume, Seigo Baba, Naomi Osakabe, Toshihiko Osawa, Makoto Oyama, Motoko Sasaki, Yoshimasa Nakamura, Junji TeraoAbstract:Abstract (−)-Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels are found in black tea, apples, and chocolate. High intake of catechins has been associated with reduced risk of cardiovascular diseases. There have been several reports concerning the bioavailability of catechins, however, the chemical structure of (−)-Epicatechin metabolites in blood, tissues, and urine remains unclear. In the present study, we purified and elucidated the chemical structure of (−)-Epicatechin metabolites in human and rat urine after oral administration. Three metabolites were purified from human urine including (−)-Epicatechin-3′- O -glucuronide, 4′- O -methyl-(−)-Epicatechin-3′- O -glucuronide, and 4′- O -methyl-(−)-Epicatechin-5 or 7- O -glucuronide, according to 1 H- and 13 C-NMR, HMBC, and LC-MS analyses. The metabolites purified from rat urine were 3′- O -methyl-(−)-Epicatechin, (−)-Epicatechin-7- O -glucuronide, and 3′- O -methyl-(−)-Epicatechin-7- O -glucuronide. These compounds were also detected in the blood of humans and rats by LC-MS. The presence of these metabolites in blood and urine suggests that catechins are metabolized and circulated in the body after administration of catechin-containing foods.
-
absorption and urinary excretion of procyanidin b2 Epicatechin 4β 8 Epicatechin in rats
Free Radical Biology and Medicine, 2002Co-Authors: Seigo Baba, Naomi Osakabe, Midori Natsume, Junji TeraoAbstract:Abstract We evaluated the bioavailability and plasma antioxidative activity after administration of procyanidin B2 [Epicatechin-(4β-8)-Epicatechin] in rats. After procyanidin B2 administration, procyanidin B2 is absorbed and excreted in urine, and a portion of the PB2 is degraded to (−)-Epicatechin and to the metabolized conjugated and/or methylated (−)-Epicatechin internally in the rat. Moreover, PB2 reduces the accumulation of lipid peroxide in plasma oxidized by copper ions.
-
Absorption and urinary excretion of (-)-Epicatechin after administration of different levels of cocoa powder or (-)-Epicatechin in rats.
Journal of Agricultural and Food Chemistry, 2001Co-Authors: Seigo Baba, Naomi Osakabe, Midori Natsume, Yuko Muto, Toshio Takizawa, Junji TeraoAbstract:(−)-Epicatechin is a major polyphenol component of cocoa powder. The absorption and urinary excretion of (−)-Epicatechin following administration of different levels of either cocoa powder (150, 750, and 1500 mg/kg) or (−)-Epicatechin (1, 5, and 10 mg/kg) were evaluated in rats. Both the sum of plasma (−)-Epicatechin metabolites at 1 h postadministration and peak plasma concentrations increased in a dose-dependent fashion. The sum of (−)-Epicatechin metabolites in urine, excreted within 18 h postadministration, also increased with dose. Moreover, the sum of (−)-Epicatechin metabolites excreted in urine reached the same level in both (−)-Epicatechin and cocoa powder administration groups for equivalent amounts of (−)-Epicatechin. These results suggest that, in the dose range examined in this study, bioavailability of (−)-Epicatechin following administration of either (−)-Epicatechin or cocoa powder shows dose dependence and that the various compounds present in cocoa powder have little effect on the bioava...
-
in vivo comparison of the bioavailability of catechin Epicatechin and their mixture in orally administered rats
Journal of Nutrition, 2001Co-Authors: Seigo Baba, Naomi Osakabe, Midori Natsume, Yuko Muto, Toshio Takizawa, Junji TeraoAbstract:: We compared levels of (+)-catechin, (-)-Epicatechin, and their metabolites in rat plasma and urine after oral administration. Rats were divided into four groups and given (+)-catechin (CA group), (-)-Epicatechin (EC group), a mixture of the two (MIX group) or deionized water. Blood samples were collected before administration and at designated time intervals thereafter. Urine samples were collected 0-24 h postadministration. (+)-Catechin, (-)-Epicatechin and their metabolites in plasma and urine were analyzed by HPLC-mass spectrometry after treatment with beta-glucuronidase and/or sulfatase. After administration, absorbed (+)-catechin and (-)-Epicatechin were mainly present in plasma as metabolites, such as nonmethylated or 3'-O-methylated conjugates. In the CA and MIX groups, the primary metabolite of (+)-catechin in plasma was glucuronide in the nonmethylated form. In the EC and MIX groups, in contrast, the primary metabolites of (-)-Epicatechin in plasma were glucuronide and sulfoglucuronide in nonmethylated forms, and sulfate in the 3'-O-methylated forms. Urinary excretion of the total amount of (-)-Epicatechin metabolites in the EC group was significantly higher than the amount of (+)-catechin metabolites in the CA group. The sum of (+)-catechin metabolites in the urine was significantly lower in the MIX group than in the CA group, and the sum of (-)-Epicatechin metabolites in the MIX group was also significantly lower than in the EC group. These results suggest that the bioavailability of (-)-Epicatechin is higher than that of (+)-catechin in rats, and that, in combination, (+)-catechin and (-)-Epicatechin might be absorbed competitively in the gastrointestinal tract of rats.
