HDHL JPI: Gut and blood microbiomics for studying the effect of a polyphenol-rich dietary pattern on intestinal permeability

Lead Research Organisation: Institute of Food Research
Department Name: Food Innovation and Health

Abstract

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Technical Summary

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Planned Impact

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Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Perth
Country Australia 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Collaboration with UMIL in studying intestinal permeability and use of biomarkers 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution QIB have measured biomarkers of systemic inflammation in baseline plasma samples and contributed to the measurement of biomarkers of gut permeability.
Collaborator Contribution UMIL have measured markers of gut permeability (multi-sugar test and circulating zonulin) and of systemic bacterial load which show good correlations.
Impact A manuscript is being prepared for publication
Start Year 2017
 
Description Development of quantitative polyphenol metabolite profiling platform 
Organisation University of Barcelona
Department Faculty of Pharmacy
Country Spain 
Sector Academic/University 
PI Contribution We synthesised and purified a series of polyphenol metabolites that are found in human peripheral blood and urine including phase-2 conjugates of food polyphenols and gut microbiota-derived catabolites and their phase-2 conjugates.
Collaborator Contribution The University of Barcelona team have been using these compounds to identify peaks appearing in LC-MS traces and to allow accurate quantification.
Impact The method is in use, publications will start to appear during 2018 and beyond.
Start Year 2017