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Francisco A Tomasbarberan - One of the best experts on this subject based on the ideXlab platform.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:Background The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. Aim of the study The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Design Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC-DAD-MS-MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Results Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8-dihydroxy-6H-dibenzo [ b,d] pyran-6-one glucuronide, an unidentified aglycone (tentatively, trihydroxy-6H-dibenzo[b,d] pyran-6-one) and hydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide. These metabolites could reach up to 18.6 μM in plasma, although a large inter-individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. Conclusion The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC–DAD–MS–MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8–dihydroxy–6H–dibenzo[b,d] pyran–6–one glucuronide, an unidentified aglycone (tentatively, trihydroxy–6H–dibenzo[b,d]pyran–6–one) and hydroxy–6–Hdibenzo[ b,d]pyran–6–one glucuronide. These metabolites could reach up to 18.6 µM in plasma, although a large inter–individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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repeated oral administration of high doses of the pomegranate ellagitannin Punicalagin to rats for 37 days is not toxic
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Begona Cerda, Francisco A Tomasbarberan, Jose J Ceron, Juan Carlos EspinAbstract:The water-soluble ellagitanin Punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (≥2 g/L), the present study evaluated the possible toxic effect of Punicalagin in Sprague−Dawley rats upon repeated oral administration of a 6% Punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five Punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the Punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found i...
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evaluation of the bioavailability and metabolism in the rat of Punicalagin an antioxidant polyphenol from pomegranate juice
European Journal of Nutrition, 2003Co-Authors: Begona Cerda, Juan Carlos Espin, Jose J Ceron, Rafael Llorach, Francisco A TomasbarberanAbstract:Background & Aims: Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of Punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of Punicalagin in the rat as an animal model. Design: Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % Punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS. Results: The daily intake of Punicalagin ranged from 0.6 to 1.2 g. Values around 3–6 % the ingested Punicalagin were excreted as identified metabolites in faeces and urine. In faeces, Punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, Punicalagin was detected at concentrations around 30 μg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides. Conclusion: As only 3–6 % of the ingested Punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO2) or accumulated in non-analysed tissues, however with only traces of Punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed.
Haji Akber Aisa - One of the best experts on this subject based on the ideXlab platform.
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dual tautomerism separation method based on asymmetric transformation gram scale preparation of high purity Punicalagin from pomegranate peel wastes
Journal of Chromatography A, 2021Co-Authors: Guangying Sun, Munire Abuduaini, Guliqire Adili, Yongxin Zhao, Haji Akber AisaAbstract:Abstract In this study, a special orthogonal separation method, named as dual-tautomerism separation (DTS), was developed for the purification of tautomeric compounds from complex matrixes. In DTS, isomers of these compounds are individually collected and asymmetrically transformed to the mixtures of isomers. After separating the mixture with an identical method, high-purity compounds can be prepared from the newly generated isomers but impurities remain in another one. To validate the effectiveness, a DTS was developed to prepare Punicalagin in gram-scale from pomegranate peel waste. Isomerization kinetic and thermodynamic of Punicalagin were accurately assayed by dynamic HPLC built on low-temperature or/and loop-based stop-flow two-dimensional liquid chromatography. After the isomerization based on it, 9.3 g of pomegranate peel extract was firstly separated on C18 column, and Fα and Fβ around α-Punicalagin and β-Punicalagin were obtained. Then, the proportion of α-Punicalagin in Fα and Fβ was optimized to 52.7% and 32.0% based on isomerization kinetics and thermodynamic. With the aid of low-temperature injection, Fα and Fβ were loaded and secondly purified. After waste recycling, totally 3.0 g of Punicalagin with the purify of 99.5% was obtained within two days, which would strongly support the resource utilization of pomegranate peel waste. Because only an individual method was employed in the two-step purification, the separation in DTS was fully compatible.
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two dimensional molecularly imprinted solid phase extraction coupled with crystallization and high performance liquid chromatography for fast semi preparative purification of tannins from pomegranate husk extract
Journal of Chromatography A, 2017Co-Authors: Guangying Sun, Yanfang Liu, Hasanjan Ahat, Aijin Shen, Xinmiao Liang, Xingya Xue, Yuqin Luo, Jian Yang, Zhaosheng Liu, Haji Akber AisaAbstract:In this study, "two dimensional" molecularly imprinted solid-phase extraction (2D-MIP-SPE) of semi-preparative grade was constructed to fast purify ellagitannins in pomegranate husk extract with the help of crystallization and reverse-phase liquid chromatgoraphy (RPLC). Ellagic acid and Punicalagin imprinted polymers were synthesized in batch mode and two semi-preparative MIP-SPE columns were individually packed. After investigaing "functional complementation", 2D-MIP-SPE was constructed using ellagic acid MIP and Punicalagin MIP-SPE as the first and second dimension, respectively. Then, pomegranate husk extract was fast divided into four fractions individually enriching in ellagic acid, granatin A, Punicalagin and ellagic acid glucoside by 2D-MIP-SPE. With the aid of crystallization and RPLC, ellagic acid (13.5mg) and Punicalagin (53.4mg) were fast obtained in 30min. Ellagic acid glucoside was purified to the purity near 100% with a recovery of 86.1%. Granatin A (92%) was directly obtained by 2D-MIP-SPE with the recovery of 81.8%. All above indicated that 2D-MIP-SPE was highly efficient in natural product purification. The concept of "functional complementation" was expected to be a useful tool in the construction of 2D-MIP-SPE.
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cost effective imprinting combining macromolecular crowding and a dummy template for the fast purification of Punicalagin from pomegranate husk extract
IEEE Journal of Solid-state Circuits, 2016Co-Authors: Guangying Sun, Yongxin Zhao, Yuqin Luo, Jian Yang, Zhaosheng Liu, Chao Wang, Haji Akber AisaAbstract:The combination of molecular crowding and virtual imprinting was employed to develop a cost-effective method to prepare molecularly imprinted polymers. By using linear polymer polystyrene as a macromolecular crowding agent, an imprinted polymer recognizable to Punicalagin had been successfully synthesized with punicalin as the dummy template. The resulting punicalin-imprinted polymer presented a remarkable selectivity to Punicalagin with an imprinting factor of 3.17 even at extremely low consumption of the template (template/monomer ratio of 1:782). In contrast, the imprinted polymer synthesized without crowding agent, did not show any imprinting effect at so low template amount. The imprinted polymers made by combination of molecular crowding and virtual imprinting can be utilized for the fast separation of Punicalagin from pomegranate husk extract after optimizing the protocol of solid-phase extraction with the recovery of 85.3 ± 1.2%.
Begona Cerda - One of the best experts on this subject based on the ideXlab platform.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:Background The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. Aim of the study The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Design Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC-DAD-MS-MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Results Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8-dihydroxy-6H-dibenzo [ b,d] pyran-6-one glucuronide, an unidentified aglycone (tentatively, trihydroxy-6H-dibenzo[b,d] pyran-6-one) and hydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide. These metabolites could reach up to 18.6 μM in plasma, although a large inter-individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. Conclusion The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC–DAD–MS–MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8–dihydroxy–6H–dibenzo[b,d] pyran–6–one glucuronide, an unidentified aglycone (tentatively, trihydroxy–6H–dibenzo[b,d]pyran–6–one) and hydroxy–6–Hdibenzo[ b,d]pyran–6–one glucuronide. These metabolites could reach up to 18.6 µM in plasma, although a large inter–individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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repeated oral administration of high doses of the pomegranate ellagitannin Punicalagin to rats for 37 days is not toxic
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Begona Cerda, Francisco A Tomasbarberan, Jose J Ceron, Juan Carlos EspinAbstract:The water-soluble ellagitanin Punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (≥2 g/L), the present study evaluated the possible toxic effect of Punicalagin in Sprague−Dawley rats upon repeated oral administration of a 6% Punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five Punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the Punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found i...
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evaluation of the bioavailability and metabolism in the rat of Punicalagin an antioxidant polyphenol from pomegranate juice
European Journal of Nutrition, 2003Co-Authors: Begona Cerda, Juan Carlos Espin, Jose J Ceron, Rafael Llorach, Francisco A TomasbarberanAbstract:Background & Aims: Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of Punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of Punicalagin in the rat as an animal model. Design: Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % Punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS. Results: The daily intake of Punicalagin ranged from 0.6 to 1.2 g. Values around 3–6 % the ingested Punicalagin were excreted as identified metabolites in faeces and urine. In faeces, Punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, Punicalagin was detected at concentrations around 30 μg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides. Conclusion: As only 3–6 % of the ingested Punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO2) or accumulated in non-analysed tissues, however with only traces of Punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed.
Juan Carlos Espin - One of the best experts on this subject based on the ideXlab platform.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:Background The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. Aim of the study The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Design Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC-DAD-MS-MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Results Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8-dihydroxy-6H-dibenzo [ b,d] pyran-6-one glucuronide, an unidentified aglycone (tentatively, trihydroxy-6H-dibenzo[b,d] pyran-6-one) and hydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide. These metabolites could reach up to 18.6 μM in plasma, although a large inter-individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. Conclusion The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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the potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy 6h dibenzopyran 6 one derivatives by the colonic microflora of healthy humans
European Journal of Nutrition, 2004Co-Authors: Begona Cerda, Juan Carlos Espin, S Parra, P. Martínez, Francisco A TomasbarberanAbstract:The antiatherogenic activity of pomegranate juice has been attributed to its antioxidant polyphenols. The most potent in vitro antioxidant polyphenol from this juice is the ellagitannin Punicalagin. However, the bioavailability of ellagitannins, including Punicalagin, has not been previously described in humans. The present work aims to evaluate, in healthy humans, the bioavailability and metabolism of pomegranate juice ellagitannins, to assess their effect on several blood parameters (including cardiovascular risk disease markers) and to compare the antioxidant activity of Punicalagin with that of the in vivo generated metabolites. Six healthy subjects (four men and two women) consumed 1 L of pomegranate juice daily (5.58 g/L polyphenols, including 4.37 g/L Punicalagin isomers) for 5 days. The polyphenols and the in vivo generated metabolites were measured by HPLC–DAD–MS–MS. Fourteen haematological and twenty serobiochemical parameters including LDL, HDL and VLDL as well as cholesterol and triglycerides in each lipoprotein were evaluated. In vitro antioxidant activity of plasma (ABTS and FRAP assays) and urine (ABTS and DPPH) were determined. Neither Punicalagin nor ellagic acid present in the juice were detected in both plasma and urine. Three microbial ellagitannin-derived metabolites were detected: 3,8–dihydroxy–6H–dibenzo[b,d] pyran–6–one glucuronide, an unidentified aglycone (tentatively, trihydroxy–6H–dibenzo[b,d]pyran–6–one) and hydroxy–6–Hdibenzo[ b,d]pyran–6–one glucuronide. These metabolites could reach up to 18.6 µM in plasma, although a large inter–individual variability was observed. In urine, the same metabolites and their corresponding aglycones became evident after 1 day of juice consumption. Total urine excretion of metabolites ranged from 0.7 to 52.7% regarding the ingested Punicalagin. No relevant effect was observed on any blood parameter. The metabolites did not show significant antioxidant activity compared to Punicalagin from pomegranate juice. The potential systemic biological effects of pomegranate juice ingestion should be attributed to the colonic microflora metabolites rather than to the polyphenols present in the juice.
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repeated oral administration of high doses of the pomegranate ellagitannin Punicalagin to rats for 37 days is not toxic
Journal of Agricultural and Food Chemistry, 2003Co-Authors: Begona Cerda, Francisco A Tomasbarberan, Jose J Ceron, Juan Carlos EspinAbstract:The water-soluble ellagitanin Punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (≥2 g/L), the present study evaluated the possible toxic effect of Punicalagin in Sprague−Dawley rats upon repeated oral administration of a 6% Punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five Punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the Punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found i...
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evaluation of the bioavailability and metabolism in the rat of Punicalagin an antioxidant polyphenol from pomegranate juice
European Journal of Nutrition, 2003Co-Authors: Begona Cerda, Juan Carlos Espin, Jose J Ceron, Rafael Llorach, Francisco A TomasbarberanAbstract:Background & Aims: Punicalagin is an antioxidant ellagitannin of pomegranate juice. This compound is responsible for the high antioxidant activity of this juice. Nothing is known about the bioavailability and metabolism of Punicalagin or other food ellagitannins. The present work aims to evaluate the bioavailability and metabolism of Punicalagin in the rat as an animal model. Design: Two groups of rats were studied. One fed with standard rat diet (n = 5) and another with the same diet plus 6 % Punicalagin (n = 5). Samples of urine and faeces were taken during 37 days and plasma every week. The different metabolites were analysed by HPLC-MS-MS. Results: The daily intake of Punicalagin ranged from 0.6 to 1.2 g. Values around 3–6 % the ingested Punicalagin were excreted as identified metabolites in faeces and urine. In faeces, Punicalagin is transformed to hydrolysis products and partly metabolites by the rat microflora to 6H-dibenzo[b,d]pyran-6-one derivatives. In plasma, Punicalagin was detected at concentrations around 30 μg/mL, and glucuronides of methyl ether derivatives of ellagic acid were also detected. 6H-Dibenzo[b,d]pyran-6-one derivatives were also detected especially during the last few weeks of the experiment. In urine, the main metabolites observed were the 6H-dibenzo[b,d]pyran-6-one derivatives, as aglycones or glucuronides. Conclusion: As only 3–6 % of the ingested Punicalagin was detected as such or as metabolites in urine and faeces, the majority of this ellagitannin has to be converted to undetectable metabolites (i. e. CO2) or accumulated in non-analysed tissues, however with only traces of Punicalagin metabolites being detected in liver or kidney. This is the first report on the absorption of an ellagitannin and its presence in plasma. In addition, the transformation of ellagic acid derivatives to 6H-dibenzo[b,d]pyran-6-one derivatives in the rat is also confirmed.
Michael D Nelson - One of the best experts on this subject based on the ideXlab platform.
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Punicalagin promotes human villous trophoblast differentiation
Placenta, 2016Co-Authors: Baosheng Chen, Mark S. Longtine, Maria Laura Costa, Michael D NelsonAbstract:Poor differentiation of trophoblasts is associated with placental dysfunction, predisposing women to multiple pregnancy disorders. Punicalagin, a prominent ellagitannin in pomegranate juice has been shown to exert anti-apoptosis and anti-oxidative effects in human trophoblasts. We hypothesized that Punicalagin modulates trophoblast differentiation. We found that Punicalagin-treated primary trophoblast showed reduced E-cadherin, higher Syncytin 1, more β-hCG, and increased GCM1, an upstream regulator of β-hCG. Punicalagin exposure of villous explants enhanced the number of cytotrophoblasts expressing the proliferation marker Ki67. We conclude that Punicalagin enhances trophoblast differentiation and speculate that Punicalagin might be used therapeutically in pregnancies at risk for placental dysfunction.
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Punicalagin a polyphenol in pomegranate juice downregulates p53 and attenuates hypoxia induced apoptosis in cultured human placental syncytiotrophoblasts
American Journal of Physiology-endocrinology and Metabolism, 2013Co-Authors: Baosheng Chen, Mark S. Longtine, Michael D NelsonAbstract:Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and Punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that Punicalagin limits trophoblast injury in vitro by regulating the levels of p53. We examined the expression of p53, mouse double minute 2 homolog, p21, hypoxia-inducible factor (HIF) α, and selected members of the B cell lymphoma 2 (BCL2) family of proteins in cultured syncytiotrophoblasts exposed to ≤1% oxygen in the absence or presence of Punicalagin. We found that Punicalagin attenuated hypoxia-induced apoptosis in syncytiotrophoblasts, as quantified by levels of cleaved poly-ADP ribose polymerase. This protective effect was in part mediated by reduced p53 activity shown by decreased expression of p21, lower HIF1α expression, and limited activity of caspases 9 and 3. There was no change in expression of proteins in the BCL2 family, which are also important in apoptosis. The data support a role for downregulation of p53 in the protection of human trophoblasts by Punicalagin.
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191 Punicalagin attenuates hypoxia induced apoptosis by down regulating p53 activity in cultured human placental syncytiotrophoblasts
American Journal of Obstetrics and Gynecology, 2013Co-Authors: Baosheng Chen, Mark S. Longtine, Michael D NelsonAbstract:factor expression in pregnancy Amy Wong, Hau Kwaan, William Grobman, Ivy Weiss, Cynthia Wong Northwestern University, Feinberg School of Medicine, Department of Obstetrics and Gynecology, Chicago, IL, Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL, Northwestern University, Feinberg School of Medicine, Department of Anesthesiology, Chicago, IL OBJECTIVE: Microparticles (MPs) are potent activators of the coagulation system. To investigate whether MPs originating from platelets or trophoblast cells that express tissue factor (TF) contribute to coagulation changes in pregnancy, we aimed to characterize whether pregnancy, labor, and delivery are associated with changes in the source and composition of MPs. STUDY DESIGN: Blood samples were collected in 20 non-pregnant women, 20 term pregnant women not in labor (presenting for induction or scheduled cesarean delivery), and 20 term pregnant women in labor. Two samples were collected in the pregnant groups, one prior to delivery and the second one hour after delivery. Using flow cytometry, we used CD41a and NDOG2 antibodies to identify MPs from platelets and trophoblasts, respectively, and TF antigen to identify MPs expressing tissue factor. Comparisons were made between the non-pregnant and pregnant groups, non-laboring and laboring groups, and pre-delivery and post-delivery groups within the pregnant groups. RESULTS: There was no difference among the non-pregnant, pregnant pre-delivery non-laboring, and pregnant pre-delivery laboring groups with regard to the proportion of MPs originating from platelets or expressing TF. Also, the presence of labor did not affect the proportion of MPs originating from trophoblasts. Conversely, the proportion of platelet-derived MPs present among women in labor increased after delivery (8.5 vs. 20.5%, p 0.02). CONCLUSION: In the current study, pregnancy was not associated with changes in cell origin of MPs or in the number of TF-expressing MPs. However, delivery appears to be associated with an increase in the number of platelet-derived MPs. Further investigation may determine whether this increase contributes to the clinically meaningful coagulation changes in pregnancy and the puerperium, as well as to identify other possible MP sources or antigens that may affect coagulation. 191 Punicalagin attenuates hypoxia-induced apoptosis by down regulating p53 activity in cultured human placental syncytiotrophoblasts Baosheng Chen, Mark S Longtine, D Michael Nelson Washington University School of Medicine, Department of Obstetrics and Gynecology, St. Louis, MO OBJECTIVE: Punicalagin is a promiment polyphenol in pomegranate juice (PJ), and both Punicalagin and PJ reduce oxidative stress and apoptosis in human placental trophoblasts (Chen et al. Am J Physiol 302:E1142, 2012). The mechanism for this effect is unknown. We tested the hypothesis that Punicalagin attenuates apoptosis in cultures of syncytiotrophoblasts exposed to hypoxia by regulating the expression of p53, MDM2, Hif-1 , and Bcl-2 family member proteins. STUDY DESIGN: Primary human trophoblasts were cultured in 5% CO2/air for 28 h in DMEM with 10% FBS and then for 24 h in phenolred free DMEM with 10% charcoal-stripped FBS. Syncytiotrophoblasts formed during this time, and at 52 h the cultures were exposed to 24 h of 1% oxygen with 5% CO2, 10% H2, and 84% N2, in medium containing 33.8 mM Punicalagin or 7.5 mM glucose as control. Protein extracts of cultures were harvested at 76 h and western blotting quantified expression levels of p53, MDM2, Hif-1 , Bcl-2, Bcl-XL, Bak and Bax. RESULTS: Levels of p53 were significantly decreased after exposure to Punicalagin compared to control in the syncytiotrophoblasts under hypoxia (p 0.05). Moreover, in hypoxic syncytiotrophoblast Punicalagin exposure increased expression (p 0.05) of MDM2, the major negative regulator of p53 levels, and reduced expression of Hif-1 , which interacts with p53. There were no differences in expression between Punicalagin-exposed and control exposed syncytiotrophoblasts for any of the four proteins of the Bcl-2 family examined. CONCLUSION: Punicalagin, a prominent polyphenol in pomegranate juice, reduces p53 activity and modulates the p53 pathway to limit, in part, hypoxia-induced apoptosis in syncytiotrophoblasts. NIH RO1 HD 29190.
