Skip to main content
Erschienen in: European Journal of Nutrition 3/2013

01.04.2013 | Original Contribution

Distribution of procyanidins and their metabolites in rat plasma and tissues in relation to ingestion of procyanidin-enriched or procyanidin-rich cocoa creams

verfasst von: Aida Serra, Alba Macià, Laura Rubió, Neus Anglès, Nàdia Ortega, José Ramón Morelló, Maria-Paz Romero, Maria-José Motilva

Erschienen in: European Journal of Nutrition | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Procyanidins are extensively metabolized via phase-II and microbial enzymes. However, their distribution in the body is not well characterized.

Aim

This study investigates the distribution of procyanidins (monomers and dimers) and their phase-II metabolites in plasma and tissues (thymus, heart, liver, testicle, lung, kidney, spleen and brain).

Methods

Wistar rats were fed with 1 g of cocoa cream (CC), 50 mg of procyanidin hazelnut skin extract (PE) and 50 mg PE in 1 g CC (PECC). The rats were killed at 0, 1, 1.5, 2, 3, 4 and 18 h after gavage, and the plasma and tissues were analyzed by UPLC–MS/MS.

Results

Epicatechin–glucuronide was the main metabolite in the plasma after the CC intake, with C max at 423 nM and t max at 2 h, and methyl catechin–glucuronide (301 nM, 2 h) was the main metabolite in the plasma after the PE intake. As a result of the PECC enrichment, epicatechin–glucuronide (452 nM, 1.5 h) and catechin–glucuronide (297 nM, 2 h) were the main metabolites in the plasma. Methyl catechin–glucuronide was found in the liver after PE (8 nmol/g tissue, 4 h) and PECC (8 nmol/g, 1.5 h). The kidney was found to contain a high concentration of phase-II metabolites of procyanidins and is therefore thought to be the main site of metabolism of the compounds. Methyl catechin–sulfate (6.4 nmol/g, 4 h) was only quantified in the brain and after PE intake. Catechin metabolites were not found in the spleen or heart. Phenolic acids were detected in all tissues.

Conclusions

The formulation of a product enriched or fortified with procyanidins is a way to increase their bioavailability, with clear effects on the plasmatic pharmacokinetics, and a greater accumulation of phenolic metabolites in such tissues as the liver, kidney, lung and brain.
Literatur
1.
Zurück zum Zitat Allen L, de Bonist B, Dary O, Hurrell R (2006) Guidelines on food fortification with micronutrients. WHO Press, Switzerland Allen L, de Bonist B, Dary O, Hurrell R (2006) Guidelines on food fortification with micronutrients. WHO Press, Switzerland
2.
Zurück zum Zitat Kaur S, Das M (2011) Functional foods: an overview. Food Sci Biotechnol 20:861–875CrossRef Kaur S, Das M (2011) Functional foods: an overview. Food Sci Biotechnol 20:861–875CrossRef
3.
Zurück zum Zitat Hasler CM, Brown AC (2009) Position of the American Dietetic Association: functional foods. J Am Diet Assoc 109:735–746CrossRef Hasler CM, Brown AC (2009) Position of the American Dietetic Association: functional foods. J Am Diet Assoc 109:735–746CrossRef
4.
Zurück zum Zitat Faridi Z, Njike VY, Dutta S, Ali A, Katz DL (2008) Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr 88:58–63 Faridi Z, Njike VY, Dutta S, Ali A, Katz DL (2008) Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr 88:58–63
5.
Zurück zum Zitat Gupta AK, Savopoulos CG, Ahuja J, Hatzitolios AI (2011) Role of phytosterols in lipid-lowering: current perspectives. QJM 104:301–308CrossRef Gupta AK, Savopoulos CG, Ahuja J, Hatzitolios AI (2011) Role of phytosterols in lipid-lowering: current perspectives. QJM 104:301–308CrossRef
6.
Zurück zum Zitat Franck A (2006) Oligofructose-enriched inulin stimulates calcium absorption and bone mineralisation. Nutr Bull 31:341–345CrossRef Franck A (2006) Oligofructose-enriched inulin stimulates calcium absorption and bone mineralisation. Nutr Bull 31:341–345CrossRef
7.
Zurück zum Zitat Bosscher D, Van Loo J, Franck A (2006) Inulin and oligofructose as functional ingredients to improve bone mineralization. Int Dairy J 16:1092–1097CrossRef Bosscher D, Van Loo J, Franck A (2006) Inulin and oligofructose as functional ingredients to improve bone mineralization. Int Dairy J 16:1092–1097CrossRef
8.
Zurück zum Zitat Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676 Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676
9.
Zurück zum Zitat Schroeter H, Heiss C, Spencer JPE, Keen CL, Lupton JR, Schmitz HH (2010) Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Asp Med 31:546–557CrossRef Schroeter H, Heiss C, Spencer JPE, Keen CL, Lupton JR, Schmitz HH (2010) Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Asp Med 31:546–557CrossRef
10.
Zurück zum Zitat Shoji T, Masumoto S, Moriichi N, Akiyama H, Kanda T, Ohtake Y, Goda Y (2006) Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high-performance liquid chromatography/tandem mass spectrometry. J Agric Food Chem 54:884–892CrossRef Shoji T, Masumoto S, Moriichi N, Akiyama H, Kanda T, Ohtake Y, Goda Y (2006) Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high-performance liquid chromatography/tandem mass spectrometry. J Agric Food Chem 54:884–892CrossRef
11.
Zurück zum Zitat Okushio K, Suzuki M, Matsumoto N, Nanjo F, Hara Y (1999) Identification of (−)-epicatechin metabolites and their metabolic fate in the rat. Drug Metab Dispos 27:309–316 Okushio K, Suzuki M, Matsumoto N, Nanjo F, Hara Y (1999) Identification of (−)-epicatechin metabolites and their metabolic fate in the rat. Drug Metab Dispos 27:309–316
12.
Zurück zum Zitat Fernández-Murga L, Tarín JJ, García-Perez MA, Cano A (2011) The impact of chocolate on cardiovascular health. Maturitas 69:312–321CrossRef Fernández-Murga L, Tarín JJ, García-Perez MA, Cano A (2011) The impact of chocolate on cardiovascular health. Maturitas 69:312–321CrossRef
13.
Zurück zum Zitat Ortega N, Reguant J, Romero MP, Macià A, Motilva MJ (2009) Effect of fat content on the digestibility and bioaccessibility of cocoa polyphenol by an in vitro digestion model. J Agric Food Chem 57:5743–5749CrossRef Ortega N, Reguant J, Romero MP, Macià A, Motilva MJ (2009) Effect of fat content on the digestibility and bioaccessibility of cocoa polyphenol by an in vitro digestion model. J Agric Food Chem 57:5743–5749CrossRef
14.
Zurück zum Zitat Serra A, Macià A, Romero MP, Salvadó M, Bustos M, Fernández-Larrea J, Motilva MJ (2009) Determination of procyanidins and their metabolites in plasma samples by improved liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 877:1169–1176CrossRef Serra A, Macià A, Romero MP, Salvadó M, Bustos M, Fernández-Larrea J, Motilva MJ (2009) Determination of procyanidins and their metabolites in plasma samples by improved liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 877:1169–1176CrossRef
15.
Zurück zum Zitat Martí M, Pantaleón A, Rozek A, Soler A, Valls J, Macià A, Romero MP, Motilva MJ (2010) Rapid analysis of procyanidins and anthocyanins in plasma by microelution SPE and ultra-HPLC. J Sep Sci 33:2841–2853CrossRef Martí M, Pantaleón A, Rozek A, Soler A, Valls J, Macià A, Romero MP, Motilva MJ (2010) Rapid analysis of procyanidins and anthocyanins in plasma by microelution SPE and ultra-HPLC. J Sep Sci 33:2841–2853CrossRef
16.
Zurück zum Zitat Serra A, Macià A, Romero MP, Anglès N, Morelló JR, Motilva MJ (2011) Distribution of procyanidins and their metabolites in rat plasma and tissues after an acute intake of hazelnut extract. Food Funct 2:562–568CrossRef Serra A, Macià A, Romero MP, Anglès N, Morelló JR, Motilva MJ (2011) Distribution of procyanidins and their metabolites in rat plasma and tissues after an acute intake of hazelnut extract. Food Funct 2:562–568CrossRef
17.
Zurück zum Zitat Serra A, Macià A, Romero MP, Valls J, Bladé C, Arola L, Motilva MJ (2010) Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models. Br J Nutr 103:944–952CrossRef Serra A, Macià A, Romero MP, Valls J, Bladé C, Arola L, Motilva MJ (2010) Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models. Br J Nutr 103:944–952CrossRef
18.
Zurück zum Zitat Holt RR, Lazarus SA, Cameron Sullards M, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL (2002) Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76:798–804 Holt RR, Lazarus SA, Cameron Sullards M, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL (2002) Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76:798–804
19.
Zurück zum Zitat Baba S, Osakabe N, Natsume M, Terao J (2002) Absorption and urinary excretion of procyanidin B2 [epicatechin-(4β-8)-epicatechin] in rats. Free Radic Biol Med 33:142–148CrossRef Baba S, Osakabe N, Natsume M, Terao J (2002) Absorption and urinary excretion of procyanidin B2 [epicatechin-(4β-8)-epicatechin] in rats. Free Radic Biol Med 33:142–148CrossRef
20.
Zurück zum Zitat Zhu QY, Holt RR, Lazarus SA, Ensunsa JL, Hammerstone JF, Schmitz HH, Keen CL (2002) Stability of the flavan-3-ols epicatechin and catechin and related dimeric procyanidins derived from cocoa. J Agric Food Chem 50:1700–1705CrossRef Zhu QY, Holt RR, Lazarus SA, Ensunsa JL, Hammerstone JF, Schmitz HH, Keen CL (2002) Stability of the flavan-3-ols epicatechin and catechin and related dimeric procyanidins derived from cocoa. J Agric Food Chem 50:1700–1705CrossRef
21.
Zurück zum Zitat Hackett AM, Shaw IC, Griffiths LA (1982) 3′-O-methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate: new urinary metabolites of (+)-catechin in the rat and the marmoset. Experientia 38:538–540CrossRef Hackett AM, Shaw IC, Griffiths LA (1982) 3′-O-methyl-(+)-catechin glucuronide and 3′-O-methyl-(+)-catechin sulphate: new urinary metabolites of (+)-catechin in the rat and the marmoset. Experientia 38:538–540CrossRef
22.
Zurück zum Zitat Natsume M, Osakabe N, Oyama M, Sasaki M, Baba S, Nakamura Y, Osawa T, Terao J (2003) Structures of (−)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-epicatechin: differences between human and rat. Free Radic Biol Med 34:840–849CrossRef Natsume M, Osakabe N, Oyama M, Sasaki M, Baba S, Nakamura Y, Osawa T, Terao J (2003) Structures of (−)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-epicatechin: differences between human and rat. Free Radic Biol Med 34:840–849CrossRef
23.
Zurück zum Zitat Tsang C, Auger C, Mullen W, Bornet A, Rouanet J-, Crozier A, Teissedre P (2005) The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Br J Nutr 94:170–181CrossRef Tsang C, Auger C, Mullen W, Bornet A, Rouanet J-, Crozier A, Teissedre P (2005) The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Br J Nutr 94:170–181CrossRef
24.
Zurück zum Zitat Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, Rice-Evans CA (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 33:1693–1702CrossRef Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, Rice-Evans CA (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 33:1693–1702CrossRef
25.
Zurück zum Zitat Urpi-Sarda M, Ramiro-Puig E, Khan N, Ramos-Romero S, Llorach R, Castell M, Gonzalez-Manzano S, Santos-Buelga C, Andres-Lacueva C (2010) Distribution of epicatechin metabolites in lymphoid tissues and testes of young rats with a cocoa-enriched diet. Br J Nutr 103:1393–1397CrossRef Urpi-Sarda M, Ramiro-Puig E, Khan N, Ramos-Romero S, Llorach R, Castell M, Gonzalez-Manzano S, Santos-Buelga C, Andres-Lacueva C (2010) Distribution of epicatechin metabolites in lymphoid tissues and testes of young rats with a cocoa-enriched diet. Br J Nutr 103:1393–1397CrossRef
26.
Zurück zum Zitat Fraga CG, Litterio MC, Prince PD, Calabró V, Piotrkowski B, Galleano M (2011) Cocoa flavanols: effects on vascular nitric oxide and blood pressure. J Clin Biochem Nutr 48:63–67CrossRef Fraga CG, Litterio MC, Prince PD, Calabró V, Piotrkowski B, Galleano M (2011) Cocoa flavanols: effects on vascular nitric oxide and blood pressure. J Clin Biochem Nutr 48:63–67CrossRef
27.
Zurück zum Zitat Lee KW, Kang NJ, Oak M-, Hwang MK, Kim JH, Schini-Kerth VB, Lee HJ (2008) Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1–MMP activities. Cardiovasc Res 79:34–41CrossRef Lee KW, Kang NJ, Oak M-, Hwang MK, Kim JH, Schini-Kerth VB, Lee HJ (2008) Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1–MMP activities. Cardiovasc Res 79:34–41CrossRef
28.
Zurück zum Zitat Cai Q, Li B, Gao H, Zhang J, Wang J, Yu F, Yin M, Zhang Z (2011) Grape seed procyanidin B2 inhibits human aortic smooth muscle cell proliferation and migration induced by advanced glycation end products. Biosci Biotechnol Biochem 75:1692–1697CrossRef Cai Q, Li B, Gao H, Zhang J, Wang J, Yu F, Yin M, Zhang Z (2011) Grape seed procyanidin B2 inhibits human aortic smooth muscle cell proliferation and migration induced by advanced glycation end products. Biosci Biotechnol Biochem 75:1692–1697CrossRef
29.
Zurück zum Zitat Asha Devi S, Sagar Chandrasekar BK, Manjula KR, Ishii N (2011) Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Exp Gerontol 46:958–964CrossRef Asha Devi S, Sagar Chandrasekar BK, Manjula KR, Ishii N (2011) Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Exp Gerontol 46:958–964CrossRef
30.
Zurück zum Zitat Narita K, Hisamoto M, Okuda T, Takeda S (2011) Differential neuroprotective activity of two different grape seed extracts. PLoS One 6:e14575CrossRef Narita K, Hisamoto M, Okuda T, Takeda S (2011) Differential neuroprotective activity of two different grape seed extracts. PLoS One 6:e14575CrossRef
31.
Zurück zum Zitat Li D, Wang Q, Yuan Z, Zhang L, Xu L, Cui Y, Duan K (2008) Pharmacokinetics and tissue distribution study of orientin in rat by liquid chromatography. J Pharm Biomed Anal 47:429–434CrossRef Li D, Wang Q, Yuan Z, Zhang L, Xu L, Cui Y, Duan K (2008) Pharmacokinetics and tissue distribution study of orientin in rat by liquid chromatography. J Pharm Biomed Anal 47:429–434CrossRef
32.
Zurück zum Zitat Ohkita M, Nakajima A, Ueda K, Takaoka M, Kiso Y, Matsumura Y (2005) Preventive effect of flavangenol on ischemia/reperfusion-induced acute renal failure in rats. Biol Pharm Bull 28:1655–1657CrossRef Ohkita M, Nakajima A, Ueda K, Takaoka M, Kiso Y, Matsumura Y (2005) Preventive effect of flavangenol on ischemia/reperfusion-induced acute renal failure in rats. Biol Pharm Bull 28:1655–1657CrossRef
33.
Zurück zum Zitat Lin Y, Chen S, Liu C, Nieh S (2011) The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells. J Oral Pathol Med 41:322–331CrossRef Lin Y, Chen S, Liu C, Nieh S (2011) The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells. J Oral Pathol Med 41:322–331CrossRef
34.
Zurück zum Zitat Chung Y, Huang C, Chen C, Chiang H, Chen K, Chen Y, Liu C, Chuang L, Liu M, Hsu C (2011) Grape-seed procyanidins inhibit the in vitro growth and invasion of pancreatic carcinoma cells. Pancreas 41:447–454CrossRef Chung Y, Huang C, Chen C, Chiang H, Chen K, Chen Y, Liu C, Chuang L, Liu M, Hsu C (2011) Grape-seed procyanidins inhibit the in vitro growth and invasion of pancreatic carcinoma cells. Pancreas 41:447–454CrossRef
35.
Zurück zum Zitat Jung M, Triebel S, Anke T, Richling E, Erkel G (2009) Influence of apple polyphenols on inflammatory gene expression. Mol Nutr Food Res 53:1263–1280CrossRef Jung M, Triebel S, Anke T, Richling E, Erkel G (2009) Influence of apple polyphenols on inflammatory gene expression. Mol Nutr Food Res 53:1263–1280CrossRef
Metadaten
Titel
Distribution of procyanidins and their metabolites in rat plasma and tissues in relation to ingestion of procyanidin-enriched or procyanidin-rich cocoa creams
verfasst von
Aida Serra
Alba Macià
Laura Rubió
Neus Anglès
Nàdia Ortega
José Ramón Morelló
Maria-Paz Romero
Maria-José Motilva
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
European Journal of Nutrition / Ausgabe 3/2013
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0409-2

Weitere Artikel der Ausgabe 3/2013

European Journal of Nutrition 3/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.