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Review Articles

A critical examination of human data for the biological activity of quercetin and its phase-2 conjugates

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References

  • Almeida, A. F., G. I. A. Borge, M. Piskula, A. Tudose, L. Tudoreanu, K. Valentová, G. Williamson, and C. N. Santos. 2018. Bioavailability of quercetin in humans with a focus on interindividual variation. Comprehensive Reviews in Food Science and Food Safety 17 (3):714–31. doi: 10.1111/1541-4337.12342.
  • Andres-Lacueva, C., M. Monagas, N. Khan, M. Izquierdo-Pulido, M. Urpi-Sarda, J. Permanyer, and R. M. Lamuela-Raventos. 2008. Flavanol and flavonol contents of cocoa powder products: Influence of the manufacturing process. Journal of Agricultural and Food Chemistry 56 (9):3111–7. doi: 10.1021/jf0728754.
  • Arts, I. C. W., D. P. Venema, and P. C. H. Hollman. 2003. Quantitative determination of flavonols in plant foods and biological fluids. In Methods in polyphenol analysis, ed. C. Santos-Buelga and G. Williamson, 214–28. Cambridge: Royal Society of Chemistry.
  • Awad, H. M., M. G. Boersma, S. Boeren, H. v d Woude, J. van Zanden, P. J. van Bladeren, J. Vervoort, and I. M. Rietjens. 2002. Identification of o-quinone/quinone methide metabolites of quercetin in a cellular in vitro system. FEBS Letters 520 (1–3):30–4. doi: 10.1016/s0014-5793(02)02754-0.
  • Aziz, A. A., C. A. Edwards, M. E. J. Lean, and A. Crozier. 1998. Absorption and excretion of conjugated flavonols, including quercetin-4’-O-β-glucoside and isorhamnetin-4’-O-β-glucoside by human volunteers after the consumption of onions. Free Radical Research 29 (3):257–69. doi: 10.1080/10715769800300291.
  • Baba, S., T. Furuta, M. Horie, and H. Nakagawa. 1981. Studies on drug metabolism by use of isotopes XXVI: Determination of urinary metabolites of rutin in humans. Journal of Pharmaceutical Sciences 70 (7):780–2. doi: 10.1002/jps.2600700717.
  • Baral, S., R. Pariyar, J. Kim, H. S. Lee, and J. Seo. 2017. Quercetin-3-O-glucuronide promotes the proliferation and migration of neural stem cells. Neurobiology of Aging 52:39–52. doi: 10.1016/j.neurobiolaging.2016.12.024.
  • Barber, E., M. J. Houghton, and G. Williamson. 2021. Flavonoids as human intestinal α-glucosidase inhibitors. Foods (Basel, Switzerland) 10 (8):1939. doi: 10.3390/foods10081939.
  • Barrington, R., G. Williamson, R. N. Bennett, B. D. Davis, J. S. Brodbelt, and P. A. Kroon. 2009. Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CACO-2/TC7 cell model. Journal of Functional Foods 1 (1):74–87. doi: 10.1016/j.jff.2008.09.011.
  • Barron, D., and R. K. Ibrahim. 1988a. Hydrochloric-acid and aryl-sulphatase as reagents for UV-spectral detection of 3-sulphated and 4’-sulphated flavonoids. Phytochemistry 27 (7):2335–8. doi: 10.1016/0031-9422(88)80155-9.
  • Barron, D., and R. K. Ibrahim. 1988b. Synthesis of flavonoid sulfates. III. Synthesis of 3′,4′-ortho disulfates using sulfur trioxide-trimethylamine complex, and of 3′-suIfates using aryl sulfatase. Zeitschrift Für Naturforschung C 43 (9-10):631–5. doi: 10.1515/znc-1988-9-1002.
  • Barron, D., C. Cren-Olive, and P. Needs. 2003. Chemical synthesis of flavonoid conjugates. In Methods in Polyphenol Analysis, ed. C. Santos-Buelga and G. Williamson, 187–213. Cambridge: Royal Society of Chemistry.
  • Barron, D., C. Smarrito-Menozzi, R. Fumeaux, and F. Viton. 2016. Synthesis of dietary phenolic metabolites and isotopically labeled dietary phenolics. In Flavonoids and related compounds: Bioavailability and function, ed. J.P.E. Spencer and A. Crozier, 234–80. CRC Press.Boca Raton, London and New York
  • Bartholomé, R., G. Haenen, C. H. Hollman, A. Bast, P. C. Dagnelie, D. Roos, J. Keijer, P. A. Kroon, P. W. Needs, and C. W. Arts. 2010. Deconjugation kinetics of glucuronidated phase II flavonoid metabolites by β-glucuronidase from neutrophils. Drug Metabolism and Pharmacokinetics 25 (4):379–87. doi: 10.2133/dmpk.dmpk-10-rg-002.
  • Basit, A., N. K. Neradugomma, C. Wolford, P. W. Fan, B. Murray, R. H. Takahashi, S. C. Khojasteh, B. J. Smith, S. Heyward, R. A. Totah, et al. 2020. Characterization of differential tissue abundance of major non-CYP enzymes in human. Molecular Pharmaceutics 17 (11):4114–24. doi: 10.1021/acs.molpharmaceut.0c00559.
  • Bazyar, H., J. Ahmad Zare, A. Ahangarpour, F. Zaman, S. A. Hosseini, V. Zohoori, V. Aghamohammadi, S. Yazdanfar, and M. Ghasemi Deh Cheshmeh. 2023. The effects of rutin supplement on blood pressure markers, some serum antioxidant enzymes, and quality of life in patients with type 2 diabetes mellitus compared with placebo. Frontiers in Nutrition 10:1214420. doi: 10.3389/fnut.2023.1214420.
  • Bazyar, H., L. Moradi, F. Zaman, and A. Zare Javid. 2023. The effects of rutin flavonoid supplement on glycemic status, lipid profile, atherogenic index of plasma, brain-derived neurotrophic factor (BDNF), some serum inflammatory, and oxidative stress factors in patients with type 2 diabetes mellitus: A double-blind, placebo-controlled trial. Phytotherapy Research: PTR 37 (1):271–84. doi: 10.1002/ptr.7611.
  • Beekmann, K., R. Laura, H. J. d H. Laura, L. Actis-Goretta, B. van der Burg, P. J. van Bladeren, and I. M. C. M. Rietjens. 2015. The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Food & Function 6 (4):1098–107. doi: 10.1039/c5fo00076a.
  • Beiler, J. M., and G. J. Martin. 1951. The inhibition of xanthine oxidase by flavonoids and related compounds. The Journal of Biological Chemistry 192 (2):831–4. doi: 10.1016/S0021-9258(19)77805-3.
  • Boersma, M. G., H. Woude, J. van der, S. Bogaards, J. Boeren, N. H. Vervoort, M. L. Cnubben, P. v B. van Iersel, and I. M. Rietjens. 2002. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chemical Research in Toxicology 15 (5):662–70. doi: 10.1021/tx0101705.
  • Boesch-Saadatmandi, C., A. Loboda, A. E. Wagner, A. Stachurska, A. Jozkowicz, J. Dulak, F. Döring, S. Wolffram, and G. Rimbach. 2011. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: Role of miR-155. The Journal of Nutritional Biochemistry 22 (3):293–9. doi: 10.1016/j.jnutbio.2010.02.008.
  • Boesch-Saadatmandi, C., R. T. Pospissil, A. C. Graeser, R. Canali, I. Boomgaarden, F. Doering, S. Wolffram, S. Egert, M. J. Mueller, and G. Rimbach. 2009. Effect of quercetin on paraoxonase 2 levels in RAW264.7 macrophages and in human monocytes-role of quercetin metabolism. International Journal of Molecular Sciences 10 (9):4168–77. doi: 10.3390/ijms10094168.
  • Bolton, J. L. 2014. Quinone methide bioactivation pathway: Contribution to toxicity and/or cytoprotection? Current Organic Chemistry 18 (1):61–9. doi: 10.2174/138527281801140121123046.
  • Bondonno, N. P., C. P. Bondonno, N. C. Ward, R. J. Woodman, J. M. Hodgson, and K. D. Croft. 2020. Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease. The British Journal of Nutrition 123 (2):182–9. doi: 10.1017/s0007114519002137.
  • Boyle, S. P., V. L. Dobson, S. J. Duthie, J. A. Kyle, and A. R. Collins. 2000. Absorption and DNA protective effects of flavonoid glycosides from an onion meal. European Journal of Nutrition 39 (5):213–23. doi: 10.1007/s003940070014.
  • Braune, A., M. Gütschow, W. Engst, and M. Blaut. 2001. Degradation of quercetin and luteolin by Eubacterium ramulus. Applied and Environmental Microbiology 67 (12):5558–67. doi: 10.1128/AEM.67.12.5558-5567.2001.
  • Bravo, L., L. Goya, and E. Lecumberri. 2007. LC/MS characterization of phenolic constituents of maté (Ilex paraguariensis, St. Hil.) and its antioxidant activity compared to commonly consumed beverages. Food Research International 40 (3):393–405. doi: 10.1016/j.foodres.2006.10.016.
  • Breinholt, V. M., E. A. Offord, C. Brouwer, S. E. Nielsen, K. Brøsen, and T. Friedberg. 2002. In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 40 (5):609–16. doi: 10.1016/s0278-6915(01)00125-9.
  • Cao, H., J. M. Pauff, and R. Hille. 2014. X-ray crystal structure of a xanthine oxidase complex with the flavonoid inhibitor quercetin. Journal of Natural Products 77 (7):1693–9. doi: 10.1021/np500320g.
  • Carmella, S. G., E. J. La Voie, and S. S. Hecht. 1982. Quantitative analysis of catechol and 4-methylcatechol in human urine. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 20 (5):587–90. doi: 10.1016/s0278-6915(82)80068-9.
  • Cattivelli, A., L. Nissen, F. Casciano, D. Tagliazucchi, and A. Gianotti. 2023. Impact of cooking methods of red-skinned onion on metabolic transformation of phenolic compounds and gut microbiota changes. Food & Function 14 (8):3509–25. doi: 10.1039/d3fo00085k.
  • Chabane, M. N., A. Al Ahmad, J. Peluso, C. D. Muller, and G. Ubeaud. 2009. Quercetin and naringenin transport across human intestinal Caco-2 cells. The Journal of Pharmacy and Pharmacology 61 (11):1473–83. doi: 10.1211/jpp/61.11.0006.
  • Chalet, C., B. Hollebrands, G. S. Duchateau, and P. Augustijns. 2019. Intestinal phase-II metabolism of quercetin in HT29 cells, 3D human intestinal tissues and in healthy volunteers: A qualitative comparison using LC-IMS-MS and LC-HRMS. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 49 (8):945–52. doi: 10.1080/00498254.2018.1509246.
  • Chalet, C., J. Rubbens, J. Tack, G. S. Duchateau, and P. Augustijns. 2018. Intestinal disposition of quercetin and its phase-II metabolites after oral administration in healthy volunteers. The Journal of Pharmacy and Pharmacology 70 (8):1002–8. doi: 10.1111/jphp.12929.
  • Chao, C. L., Y. C. Hou, P. D. Chao, C. S. Weng, and F. M. Ho. 2009. The antioxidant effects of quercetin metabolites on the prevention of high glucose-induced apoptosis of human umbilical vein endothelial cells. The British Journal of Nutrition 101 (8):1165–70. doi: 10.1017/S0007114508073637.
  • Chen, Y., P. Xiao, D.-S. Ou-Yang, L. Fan, D. Guo, Y.-N. Wang, Y. Han, J.-H. Tu, G. Zhou, Y.-F. Huang, et al. 2009. Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers. Clinical and Experimental Pharmacology & Physiology 36 (8):828–33. doi: 10.1111/j.1440-1681.2009.05158.x.
  • Chen, Z. J., Y. Q. Dai, S. S. Kong, F. F. Song, L. P. Li, J. F. Ye, R. W. Wang, S. Zeng, H. Zhou, and H. D. Jiang. 2013. Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. Molecular Nutrition & Food Research 57 (5):877–85. doi: 10.1002/mnfr.201200584.
  • Cialdella-Kam, L., D. C. Nieman, W. Sha, M. P. Meaney, A. M. Knab, and R. A. Shanely. 2013. Dose-response to 3 months of quercetin-containing supplements on metabolite and quercetin conjugate profile in adults. The British Journal of Nutrition 109 (11):1923–33. doi: 10.1017/S0007114512003972.
  • Clifford, M. N., and N. Kuhnert. 2022. LC–MS characterisation and quantification of known and unknown (poly)phenol metabolites—possible pitfalls and their avoidance. Molecular Nutrition & Food Research 66 (21):e2101013. doi: 10.1002/mnfr.202101013.
  • Clifford, M. N., L. J. King, A. Kerimi, M. G. Pereira-Caro, and G. Williamson. 2022. Metabolism of phenolics in coffee and plant-based foods by canonical pathways: An assessment of the role of fatty acid β-oxidation to generate biologically-active and -inactive intermediates. Critical Reviews in Food Science and Nutrition 62:1–58. doi: 10.1080/10408398.2022.2131730.
  • Collier, A. C. 2009. The ontogeny of detoxification enzymes in pediatric liver. Drug Metabolism Reviews 41:14.
  • Combet, E., M. E. Lean, J. G. Boyle, A. Crozier, and D. F. Davidson. 2011. Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors. Clinica Chimica Acta; International Journal of Clinical Chemistry 412 (1–2):165–9. doi: 10.1016/j.cca.2010.09.037.
  • Cuccioloni, M., M. Mozzicafreddo, L. Bonfili, V. Cecarini, A. M. Eleuteri, and M. Angeletti. 2009. Natural occurring polyphenols as template for drug design. Focus on serine proteases. Chemical Biology & Drug Design 74 (1):1–15. doi: 10.1111/j.1747-0285.2009.00836.x.
  • Cui, S., Q. Wu, J. Wang, M. Li, J. Qian, and S. Li. 2019. Quercetin inhibits LPS-induced macrophage migration by suppressing the iNOS/FAK/paxillin pathway and modulating the cytoskeleton. Cell Adhesion & Migration 13 (1):1–12. doi: 10.1080/193369182018.1486142.
  • Day, A. J., F. Mellon, D. Barron, G. Sarrazin, M. R. A. Morgan, and G. Williamson. 2001. Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin. Free Radical Research 35 (6):941–52. doi: 10.1080/10715760100301441.
  • Day, A. J., J. M. Gee, M. S. DuPont, I. T. Johnson, and G. Williamson. 2003. Absorption of quercetin-3-glucoside and quercetin-4’-glucoside in the rat small intestine: The role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter. Biochemical Pharmacology 65 (7):1199–206. doi: 10.1016/s0006-2952(03)00039-x.
  • Day, A. J., Y. Bao, M. R. A. Morgan, and G. Williamson. 2000. Conjugation position of quercetin glucuronides and effect on biological activity. Free Radical Biology & Medicine 29 (12):1234–43. doi: 10.1016/s0891-5849(00)00416-0.
  • de Ferrars, R. M., C. Czank, Q. Zhang, N. P. Botting, P. A. Kroon, A. Cassidy, and C. D. Kay. 2014. The pharmacokinetics of anthocyanins and their metabolites in humans. British Journal of Pharmacology 171 (13):3268–82. [doi]. doi: 10.1111/bph.12676.
  • de Vries, J. H., P. C. Hollman, I. van Amersfoort, M. R. Olthof, and M. B. Katan. 2001. Red wine is a poor source of bioavailable flavonols in men. The Journal of Nutrition 131 (3):745–8. doi: 10.1093/jn/131.3.745.
  • Del Rio, D., A. Rodriguez-Mateos, J. P. Spencer, M. Tognolini, G. Borges, and A. Crozier. 2013. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxidants & Redox Signaling 18 (14):1818–92. doi: 10.1089/ars.2012.4581.
  • de-Pascual-Teresa, S., K. L. Johnston, M. S. DuPont, K. A. O’Leary, P. W. Needs, L. M. Morgan, M. N. Clifford, Y. Bao, and G. Williamson. 2004. Quercetin metabolites down regulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. The Journal of Nutrition 134 (3):552–7. doi: 10.1093/jn/134.3.552.
  • Derlindati, E., M. Dall’Asta, D. Ardigò, F. Brighenti, I. Zavaroni, A. Crozier, and D. Del Rio. 2012. Quercetin-3-O-glucuronide affects the gene expression profile of M1 and M2a human macrophages exhibiting anti-inflammatory effects. Food & Function 3 (11):1144–52. doi: 10.1039/c2fo30127j.
  • Dietz, B. M., and J. L. Bolton. 2011. Biological reactive intermediates (BRIs) formed from botanical dietary supplements. Chemico-Biological Interactions 192 (1-2):72–80. doi: 10.1016/j.cbi.2010.10.007.
  • Domínguez-Fernández, M., P. Young Tie Yang, I. A. Ludwig, M. N. Clifford, C. Cid, and A. Rodriguez-Mateos. 2022. In vivo study of the bioavailability and metabolic profile of (poly)phenols after sous-vide artichoke consumption. Food Chemistry 367:130620. doi: 10.1016/j.foodchem.2021.130620.
  • Domínguez-Fernández, M., Y. Xu, P. Young Tie Yang, W. Alotaibi, R. Gibson, W. L. Hall, L. Barron, I. A. Ludwig, C. Cid, and A. Rodriguez-Mateos. 2021. Quantitative assessment of dietary (Poly)phenol intake: A high-throughput targeted metabolomics method for blood and urine samples. Journal of Agricultural and Food Chemistry 69 (1):537–54. doi: 10.1021/acs.jafc.0c07055.
  • Donnini, S., F. Finetti, L. Lusini, L. Morbidelli, V. Cheynier, D. Barron, G. Williamson, J. Waltenberger, and M. Ziche. 2006. Divergent effects of quercetin conjugates on angiogenesis. The British Journal of Nutrition 95 (5):1016–23. doi: 10.1079/bjn20061753.
  • Dueñas, M., H. Mingo-Chornet, J. J. Pérez-Alonso, R. Di Paola-Naranjo, A. M. González-Paramás, and C. Santos-Buelga. 2008. Preparation of quercetin glucuronides and characterization by HPLC-DAD-ESI/MS. European Food Research and Technology 227 (4):1069–76. doi: 10.1007/s00217-008-0821-2.
  • Dueñas, M., S. González-Manzano, F. Surco-Laos, A. González-Paramas, and C. Santos-Buelga. 2012. Characterization of sulfated quercetin and epicatechin metabolites. Journal of Agricultural and Food Chemistry 60 (14):3592–8. doi: 10.1021/jf2050203.
  • DuPont, M. S., R. N. Bennett, F. A. Mellon, and G. Williamson. 2002. Polyphenols from alcoholic apple cider are absorbed, metabolized and excreted by humans. The Journal of Nutrition 132 (2):172–5. doi: 10.1093/jn/132.2.172.
  • Egert, S., and E. Wisker. 2011. Quercetin Part 1-chemical structure, content in foods, daily intake and bioavailability. Ernahrungs Umschau 58 (8):416.
  • Egert, S., S. Wolffram, B. Schulze, P. Langguth, E. M. Hubbermann, K. Schwarz, B. Adolphi, A. Bosy-Westphal, G. Rimbach, and M. J. Müller. 2012. Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules. The British Journal of Nutrition 107 (4):539–46. doi: 10.1017/s0007114511003242.
  • Elferink, H., J. P. J. Bruekers, G. H. Veeneman, and T. J. Boltje. 2020. A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine. A gut feeling. Cellular and Molecular Life Sciences: CMLS 77 (23):4799–826. doi: 10.1007/s00018-020-03564-1.
  • Erlund, I., T. Kosonen, G. Alfthan, J. Mäenpää, K. Perttunen, J. Kenraali, J. Parantainen, and A. Aro. 2000. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. European Journal of Clinical Pharmacology 56 (8):545–53. doi: 10.1007/s002280000197.
  • Eseberri, I., J. Miranda, A. Lasa, A. Mosqueda-Solís, S. González-Manzano, C. Santos-Buelga, and M. P. Portillo. 2019. Effects of quercetin metabolites on triglyceride metabolism of 3T3-L1 preadipocytes and mature adipocytes. International Journal of Molecular Sciences 20 (2):264. doi: 10.3390/ijms20020264.
  • Esperester, A., and S. Nees. 2014. Method for the anti-inflammatory protection of transplants using quercetin glucuronide. Boehringer Ingelheim International GmbH. USA.
  • Ewald, C., S. Fjelkner-Modig, K. Johansson, I. Sjöholm, and B. Åkesson. 1999. Effect of processing on major flavonoids in processed onions, green beans, and peas. Food Chemistry 64 (2):231–5. doi: 10.1016/S0308-8146(98)00136-8.
  • Fabjan, N., J. Rode, I. J. Kosir, Z. Wang, Z. Zhang, and I. Kreft. 2003. Tartary buckwheat (Fagopyrum tataricum Gaertn.) as a source of dietary rutin and quercitrin. Journal of Agricultural and Food Chemistry 51 (22):6452–5. doi: 10.1021/jf034543e.
  • Fang, Y., W. Cao, F. Liang, M. Xia, S. Pan, and X. Xu. 2019. Structure affinity relationship and docking studies of flavonoids as substrates of multidrug-resistant associated protein 2 (MRP2) in MDCK/MRP2 cells. Food Chemistry 291:101–9. doi: 10.1016/j.foodchem.2019.03.111.
  • Feher, J. 2017. Quantitative human physiology: An introduction. 2nd ed. Elsevier Inc.
  • Feliciano, R. P., A. Boeres, L. Massacessi, G. Istas, M. R. Ventura, C. N. dos Santos, C. Heiss, and A. Rodriguez-Mateos. 2016. Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols. Archives of Biochemistry and Biophysics 599:31–41. doi: 10.1016/j.abb.2016.01.014.
  • Feliciano, R. P., C. E. Mills, G. Istas, C. Heiss, and A. Rodriguez-Mateos. 2017. Absorption, metabolism and excretion of cranberry (Poly) phenols in humans: A dose response study and assessment of inter-individual variability. Nutrients 9 (3):268. doi: 10.3390/nu9030268.
  • Feliciano, R. P., G. Istas, C. Heiss, and A. Rodriguez-Mateos. 2016. Plasma and urinary phenolic profiles after acute and repetitive intake of wild blueberry. Molecules (Basel, Switzerland) 21 (9):1120. doi: 10.3390/molecules21091120.
  • Ferry, D. R., A. Smith, J. Malkhandi, D. W. Fyfe, P. G. deTakats, D. Anderson, J. Baker, and D. J. Kerr. 1996. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clinical Cancer Research 2 (4):659–68.
  • Fridovich, I. 1970. Quantitative aspects of the production of superoxide anion radical by milk xanthine oxidase. The Journal of Biological Chemistry 245 (16):4053–7.
  • Fujiwara, N., R. Mukai, M. Nishikawa, S. Ikushiro, A. Murakami, and A. Ishisaka. 2023. Transfer of quercetin ingested by maternal mice to neonatal mice via breast milk. Bioscience, Biotechnology, and Biochemistry 87 (4):442–7. doi: 10.1093/bbb/zbad007.
  • Galindo, P., I. Rodriguez-Gómez, S. González-Manzano, M. Dueñas, R. Jiménez, C. Menéndez, F. Vargas, J. Tamargo, C. Santos-Buelga, F. Pérez-Vizcaíno, et al. 2012. Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation. PloS One 7 (3):e32673. doi: 10.1371/journal.pone.0032673.
  • Gauliard, B., D. Grieve, R. Wilson, A. Crozier, C. Jenkins, W. D. Mullen, and M. Lean. 2008. The effects of dietary phenolic compounds on cytokine and antioxidant production by A549 cells. Journal of Medicinal Food 11 (2):382–4. doi: 10.1089/jmf.2007.593.
  • Gerhardt, G., V. Sinnwell, and L. Kraus. 1989. Isolation of quercetin-3-glucuronide from the leaves of Vaccinium myrtillus and Vaccinium uliginosum. Planta Medica (2):200–1.
  • Gómez-Juaristi, M., S. Martínez-López, B. Sarria, L. Bravo, and R. Mateos. 2018. Absorption and metabolism of yerba maté phenolic compounds in humans. Food Chemistry 240:1028–38. doi: 10.1016/j.foodchem.2017.08.003.
  • Graefe, E. U., J. Wittig, S. Mueller, A. K. Riethling, B. Uehleke, B. Drewelow, H. Pforte, G. Jacobasch, H. Derendorf, and M. Veit. 2001. Pharmacokinetics and bioavailability of quercetin glycosides in humans. Journal of Clinical Pharmacology 41 (5):492–9. doi: 10.1177/00912700122010366.
  • Gugler, R., M. Leschik, and H. J. Dengler. 1975. Disposition of quercetin in man after single oral and intravenous doses. European Journal of Clinical Pharmacology 9 (2–3):229–34. doi: 10.1007/BF00614022.
  • Guo, X. D., D. Y. Zhang, X. J. Gao, J. Parry, K. Liu, B. L. Liu, and M. Wang. 2013. Quercetin and quercetin-3-O-glucuronide are equally effective in ameliorating endothelial insulin resistance through inhibition of reactive oxygen species-associated inflammation. Molecular Nutrition & Food Research 57 (6):1037–45. doi: 10.1002/mnfr.201200569.
  • Guo, Y., W. J. Weber, D. Yao, L. Caixeta, N. P. Zimmerman, J. Thompson, E. Block, T. G. Rehberger, B. A. Crooker, and C. Chen. 2022. Forming 4-methylcatechol as the dominant bioavailable metabolite of intraruminal rutin inhibits p-cresol production in dairy cows. Metabolites 12 (1) doi: 10.3390/metabo12010016.
  • Heiss, C., G. Istas, R. P. Feliciano, T. Weber, B. Wang, C. Favari, P. Mena, D. Del Rio, and A. Rodriguez-Mateos. 2022. Daily consumption of cranberry improves endothelial function in healthy adults: A double blind randomized controlled trial. Food & Function 13 (7):3812–24. doi: 10.1039/d2fo00080f.
  • Henning, S. M., P. W. Wang, R. P. Lee, A. Trang, G. Husari, J. P. Yang, E. M. Grojean, A. Ly, M. Hsu, D. Heber, et al. 2020. Prospective randomized trial evaluating blood and prostate tissue concentrations of green tea polyphenols and quercetin in men with prostate cancer. Food & Function 11 (5):4114–22. doi: 10.1039/d0fo00565g.
  • Herranz-López, M., I. Borrás-Linares, M. Olivares-Vicente, J. Gálvez, A. Segura-Carretero, and V. Micol. 2017. Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 25:25–8. doi: 10.1016/j.phymed.2016.12.008.
  • Ho, L., M. G. Ferruzzi, E. M. Janle, J. Wang, B. Gong, T.-Y. Chen, J. Lobo, B. Cooper, Q. L. Wu, S. T. Talcott, et al. 2013. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer’s disease. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 27 (2):769–81. doi: 10.1096/fj.12-212118.
  • Hollman, P. C. H., and I. C. W. Arts. 2000. Flavonols, flavones and flavanols—nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 80 (7):1081–93. doi: 10.1002/(SICI)1097-0010(20000515)80:7<1081::AID-JSFA566>3.0.CO;2-G.
  • Hollman, P. C. H., K. van Het Hof, L. Tijburg, and M. B. Katan. 2001. Addition of milk does not affect the absorption of flavonols from tea in man. Free Radical Research 34 (3):297–300. doi: 10.1080/10715760100300261.
  • Hong, Y. J., and A. E. Mitchell. 2006. Identification of glutathione-related quercetin metabolites in humans. Chemical Research in Toxicology 19 (11):1525–32. doi: 10.1021/tx0601758.
  • Hong, Y., and A. E. Mitchell. 2004. Metabolic profiling of flavonol metabolites in human urine by liquid chromatography and tandem mass spectrometry. Journal of Agricultural and Food Chemistry 52 (22):6794–801. doi: 10.1021/jf040274w.
  • Hu, M., Y. Huang, X. Du, G. Liu, B. Qi, and Y. Li. 2023. The synergistic effect of epigallocatechin-3-gallate and quercetin co-loaded hydrogel beads on inflammatory bowel disease. Food & Function 14 (10):4539–51. doi: 10.1039/d2fo04029h.
  • Ishisaka, A., K. Kawabata, S. Miki, Y. Shiba, S. Minekawa, T. Nishikawa, R. Mukai, J. Terao, and Y. Kawai. 2013. Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages. PloS One 8 (11):e80843. doi: 10.1371/journal.pone.0080843.
  • Ishisaka, A., R. Mukai, J. Terao, N. Shibata, and Y. Kawai. 2014. Specific localization of quercetin-3-O-glucuronide in human brain. Archives of Biochemistry and Biophysics 557:11–7. doi: 10.1016/j.abb.2014.05.025.
  • Ishizawa, K., Y. Izawa-Ishizawa, S. Ohnishi, Y. Motobayashi, K. Kawazoe, S. Hamano, K. Tsuchiya, S. Tomita, K. Minakuchi, and T. Tamaki. 2009. Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells. Journal of Pharmacological Sciences 109 (2):257–64. doi: 10.1254/jphs.08236fp.
  • Jaganath, I. B., W. Mullen, C. A. Edwards, and A. Crozier. 2006. The relative contribution of the small and large intestine to the absorption and metabolism of rutin in man. Free Radical Research 40 (10):1035–46. doi: 10.1080/10715760600771400.
  • Janisch, K. M., G. Williamson, P. Needs, and G. W. Plumb. 2004. Properties of quercetin conjugates: Modulation of LDL oxidation and binding to human serum albumin. Free Radical Research 38 (8):877–84. doi: 10.1080/10715760410001728415.
  • Jenner, A. M., J. Rafter, and B. Halliwell. 2005. Human fecal water content of phenolics: The extent of colonic exposure to aromatic compounds. Free Radical Biology & Medicine 38 (6):763–72. doi: 10.1016/j.freeradbiomed.2004.11.020.
  • Jiang, W., Z. Dai, and G. Chen. 2019. Estrogen sulfotransferase induction inhibits breast cancer cell line MCF-7 proliferation. Biomedical Journal of Scientific & Technical Research 22 (5):16960–7. doi: 10.26717/bjstr.2019.22.003812.
  • Jimenez, R., R. Lopez-Sepulveda, M. Romero, M. Toral, A. Cogolludo, F. Perez-Vizcaino, and J. Duarte. 2015. Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats. Food & Function 6 (2):409–14. doi: 10.1039/c4fo00818a.
  • Jin, D., H. Hakamata, K. Takahashi, A. Kotani, and F. Kusu. 2004. Determination of quercetin in human plasma after ingestion of commercial canned green tea by semi-micro HPLC with electrochemical detection. Biomedical Chromatography: BMC 18 (9):662–6. doi: 10.1002/bmc.370.
  • Jones, D. J. L. 2001. The identification and characterisation of quercetin metabolites in humans and rats. PhD Dissertation/Thesis, MRC Toxicology Unit, University of Leicester.
  • Kaeswurm, J. A. H., A. Scharinger, J. Teipel, and M. Buchweitz. 2021. Absorption coefficients of phenolic structures in different solvents routinely used for experiments. Molecules (Basel, Switzerland) 26 (15):4656. doi: 10.3390/molecules26154656.
  • Kahle, K., M. Kempf, P. Schreier, W. Scheppach, D. Schrenk, T. Kautenburger, D. Hecker, W. Huemmer, M. Ackermann, and E. Richling. 2011. Intestinal transit and systemic metabolism of apple polyphenols. European Journal of Nutrition 50 (7):507–22. doi: 10.1007/s00394-010-0157-0.
  • Kahle, K., M. Kraus, W. Scheppach, and E. Richling. 2005. Colonic availability of apple polyphenols–A study in ileostomy subjects. Molecular Nutrition & Food Research 49 (12):1143–50. doi: 10.1002/mnfr.200500132.
  • Kahle, K., M. Kraus, W. Scheppach, M. Ackermann, F. Ridder, and E. Richling. 2006. Studies on apple and blueberry fruit constituents: Do the polyphenols reach the colon after ingestion? Molecular Nutrition & Food Research 50 (4-5):418–23. doi: 10.1002/mnfr.200500211.
  • Kapoor, M. P., M. Moriwaki, K. Uguri, D. Timm, and Y. Kuroiwa. 2021. Bioavailability of dietary isoquercitrin-gamma-cyclodextrin molecular inclusion complex in Sprague-Dawley rats and healthy humans. Journal of Functional Foods 85:104663. doi: 10.1016/j.jff.2021.104663.
  • Kawai, Y. 2014. β-Glucuronidase activity and mitochondrial dysfunction: The sites where flavonoid glucuronides act as anti-inflammatory agents. Journal of Clinical Biochemistry and Nutrition 54 (3):145–50. doi: 10.3164/jcbn.14-9.
  • Kawai, Y., H. Tanaka, K. Murota, M. Naito, and J. Terao. 2008. Epicatechin gallate accumulates in foamy macrophages in human atherosclerotic aorta: Implication in the anti-atherosclerotic actions of tea catechins. Biochemical and Biophysical Research Communications 374 (3):527–32. doi: 10.1016/j.bbrc.2008.07.086.
  • Kawai, Y., T. Nishikawa, Y. Shiba, S. Saito, K. Murota, N. Shibata, M. Kobayashi, M. Kanayama, K. Uchida, and J. Terao. 2008. Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: Implication in the anti-atherosclerotic mechanism of dietary flavonoids. The Journal of Biological Chemistry 283 (14):9424–34. doi: 10.1074/jbc.M706571200.
  • Kay, C. D., M. N. Clifford, P. Mena, J. G. McDougall, C. Andres-Lacueva, A. Cassidy, D. Del Rio, N. Kuhnert, C. Manach, G. Pereira-Caro, et al. 2020. Special article recommendations for standardizing nomenclature for dietary (poly)phenol catabolites. The American Journal of Clinical Nutrition 112 (4):1051–68. doi: 10.1093/ajcn/nqaa204.
  • Kellett, G. L., E. Brot-Laroche, O. J. Mace, and A. Leturque. 2008. Sugar absorption in the intestine: The role of GLUT2. Annual Review of Nutrition 28 (1):35–54. doi: 10.1146/annurev.nutr.28.061807.155518.
  • Kerimi, A., and G. Williamson. 2018. Differential impact of flavonoids on redox modulation, bioenergetics, and cell signaling in normal and tumor cells: A comprehensive review. Antioxidants & Redox Signaling 29 (16):1633–59. doi: 10.1089/ars.2017.7086.
  • Kerimi, A., N. U. Kraut, J. A. da Encarnacao, and G. Williamson. 2020. The gut microbiome drives inter- and intra-individual differences in metabolism of bioactive small molecules. Scientific Reports 10 (1):19590. doi: 10.1038/s41598-020-76558-5.
  • Kimira, M., Y. Arai, K. Shimoi, and S. Watanabe. 1998. Japanese intake of flavonoids and isoflavonoids from foods. Journal of Epidemiology 8 (3):168–75. doi: 10.2188/jea.8.168.
  • Kottra, G., and H. Daniel. 2007. Flavonoid glycosides are not transported by the human Na+/glucose transporter when expressed in Xenopus laevis oocytes, but effectively inhibit electrogenic glucose uptake. The Journal of Pharmacology and Experimental Therapeutics 322 (2):829–35. doi: 10.1124/jpet.107.124040.
  • Kroon, P. A., M. N. Clifford, A. Crozier, A. J. Day, J. L. Donovan, C. Manach, and G. Williamson. 2004. How should we assess the effects of exposure to dietary polyphenols in vitro? The American Journal of Clinical Nutrition 80 (1):15–21. doi: 10.1093/ajcn/80.1.15.
  • Krumholz, L. R., and M. P. Bryant. 1986. Eubacterium oxidoreducens sp. nov. requiring H2 or formate to degrade gallate, pyrogallol, phloroglucinol and quercetin. Archives of Microbiology 144 (1):8–14. doi: 10.1007/BF00454948.
  • Krumholz, L. R., and M. P. Bryant. 1988. Characterization of the pyrogallol-phloroglucinol isomerase of Eubacterium oxidoreducens. Journal of Bacteriology 170 (6):2472–9. doi: 10.1128/jb.170.6.2472-2479.1988.
  • Krumholz, L. R., R. L. Crawford, M. E. Hemling, and M. P. Bryant. 1986. A rumen bacterium degrading quercetin and trihydroxybenzenoids with concurrent use of formate or H2. Progress in Clinical and Biological Research 213:211–4.
  • Krumholz, L. R., R. L. Crawford, M. E. Hemling, and M. P. Bryant. 1987. Metabolism of gallate and phloroglucinol in Eubacterium oxidoreducens via 3-hydroxy-5-oxohexanoate. Journal of Bacteriology 169 (5):1886–90. doi: 10.1128/jb.169.5.1886-1890.1987.
  • Kyle, J. A., P. C. Morrice, G. McNeill, and G. G. Duthie. 2007. Effects of infusion time and addition of milk on content and absorption of polyphenols from black tea. Journal of Agricultural and Food Chemistry 55 (12):4889–94. doi: 10.1021/jf070351y.
  • Labib, S., A. Erb, M. Kraus, T. Wickert, and E. Richling. 2004. The pig caecum model: A suitable tool to study the intestinal metabolism of flavonoids. Molecular Nutrition & Food Research 48 (4):326–32. doi: 10.1002/mnfr.200400022.
  • Lamuela-Raventós, R. M., M.-I. Covas, M. Fitó, J. Marrugat, and M. C. de la Torre-Boronat. 1999. Detection of dietary antioxidant phenolic compounds in human LDL. Clinical Chemistry 45 (10):1870–2. doi: 10.1093/clinchem/45.10.1870.
  • Le Sayec, M., D. Carregosa, K. Khalifa, C. de Lucia, D. Aarsland, C. N. Santos, and A. Rodriguez-Mateos. 2023. Identification and quantification of (poly)phenol and methylxanthine metabolites in human cerebrospinal fluid: Evidence of their ability to cross the BBB. Food & Function 14 (19):8893–902. doi: 10.1039/D3FO01913F.
  • Lee, J., S. E. Ebeler, J. A. Zweigenbaum, and A. E. Mitchell. 2012. UHPLC-(ESI)QTOF MS/MS profiling of quercetin metabolites in human plasma postconsumption of applesauce enriched with apple peel and onion. Journal of Agricultural and Food Chemistry 60 (34):8510–20. doi: 10.1021/jf302637t.
  • Lessard-Lord, J., P.-L. Plante, and Y. Desjardins. 2022. Purified recombinant enzymes efficiently hydrolyze conjugated urinary (poly)phenol metabolites. Food & Function 13 (21):10895–911. doi: 10.1039/D2FO02229J.
  • Li, C., W.-J. Zhang, J. Choi, and B. Frei. 2016. Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase. Redox Biology 9:220–8. doi: 10.1016/j.redox.2016.08.012.
  • Li, F., X. Y. Sun, X. W. Li, T. Yang, and L. W. Qi. 2017. Enrichment and separation of quercetin-3-O-beta-d-glucuronide from lotus leaves (nelumbo nucifera gaertn.) and evaluation of its anti-inflammatory effect. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 1040:186–91. doi: 10.1016/j.jchromb.2016.12.017.
  • Li, Q., Q. Wei, E. Yuan, J. Yang, and Z. Ning. 2014. Interaction between four flavonoids and trypsin: Effect on the characteristics of trypsin and antioxidant activity of flavonoids. International Journal of Food Science & Technology 49 (4):1063–9. doi: 10.1111/ijfs.12401.
  • Li, S. Y., J. Liu, Z. Li, L. Q. Wang, W. N. Gao, Z. Q. Zhang, and C. J. Guo. 2020. Sodium-dependent glucose transporter 1 and glucose transporter 2 mediate intestinal transport of quercetrin in Caco-2 cells. Food & Nutrition Research 64 (0):3745–3753. doi: 10.29219/fnr.v64.3745.
  • Liao, Y. R., and J. Y. Lin. 2014. Quercetin, but not its metabolite quercetin-3-glucuronide, exerts prophylactic immunostimulatory activity and therapeutic antiinflammatory effects on lipopolysaccharide-treated mouse peritoneal macrophages ex vivo. Journal of Agricultural and Food Chemistry 62 (13):2872–80. doi: 10.1021/jf405630h.
  • Lin, C. M., C. S. Chen, C. T. Chen, Y. C. Liang, and J. K. Lin. 2002. Molecular modeling of flavonoids that inhibits xanthine oxidase. Biochemical and Biophysical Research Communications 294 (1):167–72. doi: 10.1016/S0006-291X(02)00442-4.[doi];S0006-291X(02)00442-4 [pii].
  • Lodi, F., R. Jimenez, L. Moreno, P. A. Kroon, P. W. Needs, D. A. Hughes, C. Santos-Buelga, A. Gonzalez-Paramas, A. Cogolludo, R. Lopez-Sepulveda, et al. 2009. Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta. Atherosclerosis 204 (1):34–9. doi: 10.1016/j.atherosclerosis.2008.08.007.
  • Loke, W. M., J. M. Proudfoot, A. J. McKinley, P. W. Needs, P. A. Kroon, J. M. Hodgson, and K. D. Croft. 2008. Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. Journal of Agricultural and Food Chemistry 56 (10):3609–15. doi: 10.1021/jf8003042.
  • Loke, W. M., J. M. Proudfoot, S. Stewart, A. J. McKinley, P. W. Needs, P. A. Kroon, J. M. Hodgson, and K. D. Croft. 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. Biochemical Pharmacology 75 (5):1045–53. doi: 10.1016/j.bcp.2007.11.002.
  • Lotito, S. B., W. J. Zhang, C. S. Yang, A. Crozier, and B. Frei. 2011. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radical Biology & Medicine 51 (2):454–63. doi: 10.1016/j.freeradbiomed.2011.04.032.
  • Lu, Q. Y., L. F. Zhang, G. Eibl, and V. L. W. Go. 2014. Overestimation of flavonoid aglycones as a result of the ex vivo deconjugation of glucuronides by the tissue beta-glucuronidase. Journal of Pharmaceutical and Biomedical Analysis 88:364–9. doi: 10.1016/j.jpba.2013.09.013.
  • Macià, A., M.-P. Romero, A. Pedret, R. Solà, M. N. Clifford, and L. Rubió-Piqué. 2023. Assessment of human inter-individual variability of phloretin metabolites in urine after apple consumption. AppleCOR study. Food & Function 14 (23):10387–400. doi: 10.1039/D3FO02985A.
  • Macià, A., M.-P. Romero, S. Yuste, I. Ludwig, A. Pedret, R. M. Valls, P. Salamanca, R. Solà, M. José Motilva, and L. Rubió. 2022. Phenol metabolic fingerprint and selection of intake biomarkers after acute and sustained consumption of red-fleshed apple versus common apple in humans. The AppleCOR study. Food Chemistry 384:132612. doi: 10.1016/j.foodchem.2022.132612.
  • Makris, D. P., and J. T. Rossiter. 2000. Heat-induced, metal-catalyzed oxidative degradation of quercetin and rutin (quercetin 3-O-rhamnosylglucoside) in aqueous model systems. Journal of Agricultural and Food Chemistry 48 (9):3830–8. doi: 10.1021/jf0001280.
  • Makris, D. P., and J. T. Rossiter. 2001. Domestic processing of onion bulbs (Allium cepa) and asparagus spears (Asparagus officinalis): Effect on flavonol content and antioxidant status. Journal of Agricultural and Food Chemistry 49 (7):3216–22. doi: 10.1021/jf001497z.
  • Manolescu, A. R., K. Witkowska, A. Kinnaird, T. Cessford, and C. Cheeseman. 2007. Facilitated hexose transporters: New perspectives on form and function. Physiology (Bethesda, Md.) 22 (4):234–40. doi: 10.1152/physiol.00011.2007.
  • Martinez-Gonzalez, A. I., E. Alvarez-Parrilla, Á. G. Díaz-Sánchez, L. A. de la Rosa, J. A. Núñez-Gastélum, A. A. Vazquez-Flores, and G. A. Gonzalez-Aguilar. 2017. In vitro inhibition of pancreatic lipase by polyphenols: A kinetic, fluorescence spectroscopy and molecular docking study. Food Technology and Biotechnology 55 (4):519–30. doi: 10.17113/ftb.55.04.17.5138.
  • Mathrani, A., W. Yip, I. R. Sequeira-Bisson, D. Barnett, O. Stevenson, M. W. Taylor, and S. D. Poppitt. 2023. Effect of a 12-week polyphenol rutin intervention on markers of pancreatic β-cell function and gut microbiota in adults with overweight without diabetes. Nutrients 15 (15):3360. doi: 10.3390/nu15153360.
  • Mauri, P. L., L. Iemoli, C. Gardana, P. Riso, P. Simonetti, M. Porrini, and P. G. Pietta. 1999. Liquid chromatography/electrospray ionization mass spectrometric characterization of flavonol glycosides in tomato extracts and human plasma. Rapid Communications in Mass Spectrometry 13 (10):924–31. doi: 10.1002/(SICI)1097-0231(19990530)13:10<924::AID-RCM588>3.0.CO;2-G.
  • McAnlis, G. T., J. McEneny, J. Pearce, and I. S. Young. 1999. Absorption and antioxidant effects of quercetin from onions, in man. European Journal of Clinical Nutrition 53 (2):92–6. doi: 10.1038/sj.ejcn.1600682.
  • Mcdonald, M. S., M. Hughes, J. Burns, M. E. J. Lean, D. Matthews, and A. Crozier. 1998. Survey of the free and conjugated myricetin and quercetin content of red wines of different geographical origins. Journal of Agricultural and Food Chemistry 46 (2):368–75. doi: 10.1021/jf970677e.
  • Menendez, C., M. Dueñas, P. Galindo, S. González-Manzano, R. Jimenez, L. Moreno, M. J. Zarzuelo, I. Rodríguez-Gómez, J. Duarte, C. Santos-Buelga, et al. 2011. Vascular deconjugation of quercetin glucuronide: The flavonoid paradox revealed? Molecular Nutrition & Food Research 55 (12):1780–90. [doi]. doi: 10.1002/mnfr.201100378.
  • Menzies, I. S., M. J. Zuckerman, W. S. Nukajam, S. G. Somasundaram, B. Murphy, A. P. Jenkins, R. S. Crane, and G. G. Gregory. 1999. Geography of intestinal permeability and absorption. Gut 44 (4):483–9. doi: 10.1136/gut.44.4.483.
  • Miean, K. H., and S. Mohamed. 2001. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. Journal of Agricultural and Food Chemistry 49 (6):3106–12. doi: 10.1021/jf000892m.
  • Mizuma, T., K. Ohta, and S. Awazu. 1994. The beta-anomeric and glucose preferences of glucose transport carrier for intestinal active absorption of monosaccharide conjugates. Biochimica et Biophysica Acta 1200 (2):117–22. doi: 10.1016/0304-4165(94)90125-2.
  • Mizuma, T., K. Ohta, M. Hayashi, and S. Awazu. 1993. Comparative study of active absorption by the intestine and disposition of anomers of sugar-conjugated compounds. Biochemical Pharmacology 45 (7):1520–3. doi: 10.1016/0006-2952(93)90053-y.
  • Mochizuki, M., K. Kajiya, J. Terao, K. Kaji, S. Kumazawa, T. Nakayama, and K. Shimoi. 2004. Effect of quercetin conjugates on vascular permeability and expression of adhesion molecules. BioFactors (Oxford, England) 22 (1-4):201–4. doi: 10.1002/biof.5520220142.
  • Mohos, V., E. Fliszár-Nyúl, O. Ungvári, K. Kuffa, P. W. Needs, P. A. Kroon, Á. Telbisz, C. Özvegy-Laczka, and M. Poór. 2020. Inhibitory effects of quercetin and its main methyl, sulfate, and glucuronic acid conjugates on cytochrome P450 enzymes, and on OATP, BCRP and MRP2 transporters. Nutrients 12 (8):2306. doi: 10.3390/nu12082306.
  • Moon, J. H., R. Nakata, S. Oshima, T. Inakuma, and J. Terao. 2000. Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 279 (2):R461–R467. doi: 10.1152/ajpregu.2000.279.2.R461.
  • Moon, Y. J., L. Wang, R. DiCenzo, and M. E. Morris. 2008. Quercetin pharmacokinetics in humans. Biopharmaceutics & Drug Disposition 29 (4):205–17. doi: 10.1002/bdd.605.
  • Morand, C., V. Crespy, C. Manach, C. Besson, C. Demigné, and C. Rémésy. 1998. Plasma metabolites of quercetin and their antioxidant properties. The American Journal of Physiology 275 (1):R212–R219. doi: 10.1152/ajpregu.1998.275.1.R212.
  • Mukai, R., K. Kawabata, S. Otsuka, A. Ishisaka, Y. Kawai, Z. S. Ji, H. Tsuboi, and J. Terao. 2012. Effect of quercetin and its glucuronide metabolite upon 6-hydroxydopamine-induced oxidative damage in Neuro-2a cells. Free Radical Research 46 (8):1019–28. doi: 10.3109/10715762.2012.673720.
  • Mullen, W. 2009. Investigation of the fate of dietary flavonols in humans and rats using HPLC-MS2 techniques. PhD diss. University of Glasgow.
  • Mullen, W., A. Boitier, A. J. Stewart, and A. Crozier. 2004. Flavonoid metabolites in human plasma and urine after the consumption of red onions: Analysis by liquid chromatography with photodiode array and full scan tandem mass spectrometric detection. Journal of Chromatography. A 1058 (1-2):163–8. doi: 10.1016/S0021-9673(04)01476-1.
  • Mullen, W., C. A. Edwards, and A. Crozier. 2006. Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions. The British Journal of Nutrition 96 (1):107–16. doi: 10.1079/bjn20061809.
  • Mullen, W., G. Borges, M. E. Lean, S. A. Roberts, and A. Crozier. 2010. Identification of metabolites in human plasma and urine after consumption of a polyphenol-rich juice drink. Journal of Agricultural and Food Chemistry 58 (4):2586–95. doi: 10.1021/jf904096v.
  • Munroe, D. G., and P. L. Chang. 1987. Tissue-specific expression of human arylsulfatase-C isozymes and steroid sulfatase. Am J Hum Genet 40 (2):102–14.
  • Murakami, A., H. Ashida, and J. Terao. 2008. Multitargeted cancer prevention by quercetin. Cancer Letters 269 (2):315–25. doi: 10.1016/j.canlet.2008.03.046.
  • Murota, K., N. Matsuda, Y. Kashino, Y. Fujikura, T. Nakamura, Y. Kato, R. Shimizu, S. Okuyama, H. Tanaka, T. Koda, et al. 2010. Alpha-oligoglucosylation of a sugar moiety enhances the bioavailability of quercetin glucosides in humans. Archives of Biochemistry and Biophysics 501 (1):91–7. doi: 10.1016/j.abb.2010.06.036.
  • Nagao, A., M. Seki, and H. Kobayashi. 1999. Inhibition of xanthine oxidase by flavonoids. Bioscience, Biotechnology, and Biochemistry 63 (10):1787–90. doi: 10.1271/bbb.63.1787.
  • Nakamura, T., K. Murota, S. Kumamoto, K. Misumi, N. Bando, S. Ikushiro, N. Takahashi, K. Sekido, Y. Kato, and J. Terao. 2014. Plasma metabolites of dietary flavonoids after combination meal consumption with onion and tofu in humans. Molecular Nutrition & Food Research 58 (2):310–7. doi: 10.1002/mnfr.201300234.
  • Nalewajko-Sieliwoniuk, E., M. Hryniewicka, D. Jankowska, A. Kojło, M. Kamianowska, and M. Szczepański. 2020. Dispersive liquid-liquid microextraction coupled to liquid chromatography tandem mass spectrometry for the determination of phenolic compounds in human milk. Food Chemistry 327:126996. doi: 10.1016/j.foodchem.2020.126996.
  • Németh, K., G. W. Plumb, J.-G. Berrin, N. Juge, R. Jacob, H. Y. Naim, G. Williamson, D. M. Swallow, and P. A. Kroon. 2003. Deglycosylation by small intestinal epithelial cell β-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. European Journal of Nutrition 42 (1):29–42. doi: 10.1007/s00394-003-0397-3.
  • Nielsen, S. E., V. Breinholt, U. Justesen, C. Cornett, and L. O. Dragsted. 1998. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 28 (4):389–401. doi: 10.1080/004982598239498.
  • Nigam, S. K., K. T. Bush, G. Martovetsky, S. Y. Ahn, H. C. Liu, E. Richard, V. Bhatnagar, and W. Wu. 2015. The organic anion transporter (OAT) family: A systems biology perspective. Physiological Reviews 95 (1):83–123. doi: 10.1152/physrev.00025.2013.
  • Nishijima, T., Y. Takida, Y. Saito, T. Ikeda, and K. Iwai. 2015. Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects. The British Journal of Nutrition 113 (10):1531–8. doi: 10.1017/s0007114515000537.
  • Nishikawa, M., Y. Kada, M. Kimata, T. Sakaki, and S. Ikushiro. 2022. Comparison of metabolism and biological properties among positional isomers of quercetin glucuronide in LPS- and RANKL-challenged RAW264.7 cells. Bioscience, Biotechnology, and Biochemistry 86 (12):1670–9. doi: 10.1093/bbb/zbac150.
  • Nishimuro, H., H. Ohnishi, M. Sato, M. Ohnishi-Kameyama, I. Matsunaga, S. Naito, K. Ippoushi, H. Oike, T. Nagata, H. Akasaka, et al. 2015. Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients 7 (4):2345–58. doi: 10.3390/nu7042345.
  • Nuka, E., M. Takahashi, M. Okitsu, C. Nayama, H. Nishijima, R. Sogawa, K. Kawabata, J. Terao, and R. Mukai. 2022. Lowering effect of combined sweet potato and onion intake on plasma quercetin concentration and underlying mechanism involving intestinal β-glucosidase activity. Bioscience, Biotechnology, and Biochemistry 86 (12):1695–8. doi: 10.1093/bbb/zbac155.
  • Ohara, K., H. Wakabayashi, Y. Taniguchi, K. Shindo, H. Yajima, and A. Yoshida. 2013. Quercetin-3-O-glucuronide induces ABCA1 expression by LXR alpha activation in murine macrophages. Biochemical and Biophysical Research Communications 441 (4):929–34. doi: 10.1016/j.bbrc.2013.10.168.
  • Ohnishi, R., H. Ito, N. Kasajima, M. Kaneda, R. Kariyama, H. Kumon, T. Hatano, and T. Yoshida. 2006. Urinary excretion of anthocyanins in humans after cranberry juice ingestion. Bioscience, Biotechnology, and Biochemistry 70 (7):1681–7. doi: 10.1271/bbb.60023.
  • Okoko, T., and I. F. Oruambo. 2009. Inhibitory activity of quercetin and its metabolite on lipopolysaccharide-induced activation of macrophage U937 cells. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 47 (4):809–12. doi: 10.1016/j.fct.2009.01.013.
  • O’Leary, K. A., A. J. Day, P. W. Needs, F. A. Mellon, N. M. O’Brien, and G. Williamson. 2003. Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: The role of human β-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. Biochemical Pharmacology 65 (3):479–91. doi: 10.1016/s0006-2952(02)01510-1.
  • O’Leary, K. A., A. J. Day, P. W. Needs, W. S. Sly, N. M. O’Brien, and G. Williamson. 2001. Flavonoid glucuronides are substrates for human liver β-glucuronidase. FEBS Letters 503 (1):103–6. doi: 10.1016/s0014-5793(01)02684-9.
  • Omar, K., M. H. Grant, C. Henderson, and D. G. Watson. 2014. The complex degradation and metabolism of quercetin in rat hepatocyte incubations. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 44 (12):1074–82. doi: 10.3109/00498254.2014.932032.
  • O’Reilly, J. D., A. I. Mallet, G. T. McAnlis, I. S. Young, B. Halliwell, T. A. Sanders, and H. Wiseman. 2001. Consumption of flavonoids in onions and black tea: Lack of effect on F2-isoprostanes and autoantibodies to oxidized LDL in healthy humans. The American Journal of Clinical Nutrition 73 (6):1040–4. doi: 10.1093/ajcn/73.6.1040.
  • Ottaviani, J. I., R. Y. Fong, G. Borges, H. Schroeter, and A. Crozier. 2018. Use of LC-MS for the quantitative analysis of (poly)phenol metabolites does not necessarily yield accurate results: Implications for assessing existing data and conducting future research. Free Radical Biology & Medicine 124:97–103. doi: 10.1016/j.freeradbiomed.2018.05.092.
  • Pacifici, G. M. 2005. Pharmacokinetics of antivirals in neonate. Early Human Development 81 (9):773–80. doi: 10.1016/j.earlhumdev.2005.06.001.
  • Park, J. Y., M. S. Lim, S. I. Kim, H. J. Lee, S. S. Kim, Y. S. Kwon, and W. Chun. 2016. Quercetin-3-O-beta-D-glucuronide suppresses lipopolysaccharide-induced JNK and ERK phosphorylation in LPS-challenged RAW264.7 cells. Biomolecules & Therapeutics 24 (6):610–5. doi: 10.4062/biomolther.2016.026.
  • Park, J.-Y., S.-I. Kim, H. J. Lee, S.-S. Kim, Y.-S. Kwon, and W. Chun. 2016. Isorhamnetin-3-O-glucuronide suppresses JNK and p38 activation and increases heme-oxygenase-1 in lipopolysaccharide-challenged RAW264.7 cells. Drug Development Research 77 (3):143–51. doi: 10.1002/ddr.21301.
  • Pei, S., Y. Dou, W. Zhang, D. Qi, Y. Li, M. Wang, W. Li, H. Shi, Z. Gao, C. Yao, et al. 2022. O-Sulfation disposition of curcumin and quercetin in SULT1A3 overexpressing HEK293 cells: The role of arylsulfatase B in cellular O-sulfation regulated by transporters. Food & Function 13 (20):10558–73. doi: 10.1039/d2fo01436j.
  • Pereira-Caro, G., S. Cáceres-Jimenez, L. Bresciani, P. Mena, T. M. Almutairi, S. Dobani, L. Kirsty Pourshahidi, C. I. R. Gill, J. M. Moreno Rojas, M. N. Clifford, et al. 2023. Excretion by subjects on a low (poly)phenol diet of phenolic gut microbiota catabolites sequestered in tissues or associated with catecholamines and surplus amino acids. International Journal of Food Sciences and Nutrition 74 (4):532–43. doi: 10.1080/09637486.2023.2226369.
  • Perez, A., S. Gonzalez-Manzano, R. Jimenez, R. Perez-Abud, J. M. Haro, A. Osuna, C. Santos-Buelga, J. Duarte, and F. Perez-Vizcaino. 2014. The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: Correlation with beta-glucuronidase activity. Pharmacological Research 89:11–8. doi: 10.1016/j.phrs.2014.07.005.
  • Peron, G., S. Sut, A. Pellizzaro, P. Brun, D. Voinovich, I. Castagliuolo, and S. Dall’Acqua. 2017. The antiadhesive activity of cranberry phytocomplex studied by metabolomics: Intestinal PAC-A metabolites but not intact PAC-A are identified as markers in active urines against uropathogenic Escherichia coli. Fitoterapia 122:67–75. doi: 10.1016/j.fitote.2017.08.014.
  • Pimpão, R. C., M. R. Ventura, R. B. Ferreira, G. Williamson, and C. N. Santos. 2015. Phenolic sulfates as new and highly abundant metabolites in human plasma after ingestion of a mixed berry fruit puree. The British Journal of Nutrition 113 (3):454–63. doi: 10.1017/S0007114514003511.
  • Pratheeshkumar, P., A. Budhraja, Y. O. Son, X. Wang, Z. Zhang, S. Ding, L. Wang, A. Hitron, J. C. Lee, M. Xu, et al. 2012. Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways. PloS One 7 (10):e47516. doi: 10.1371/journal.pone.0047516.
  • Ramešová, S., R. Sokolová, I. Degano, J. Bulíčková, J. Zabka, and M. Gál. 2012. On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions. Analytical and Bioanalytical Chemistry 402 (2):975–82. doi: 10.1007/s00216-011-5504-3.
  • Ranka, S., J. M. Gee, L. Biro, G. Brett, S. Saha, P. Kroon, J. Skinner, A. R. Hart, A. Cassidy, M. Rhodes, et al. 2008. Development of a food frequency questionnaire for the assessment of quercetin and naringenin intake. European Journal of Clinical Nutrition 62 (9):1131–8. doi: 10.1038/sj.ejcn.1602827.
  • Raza, M. A., and D. Shahwar. 2013. Trypsin inhibitory potential and microbial transformation of rutin isolated from Citrus sinensis. Medicinal Chemistry Research 22 (8):3698–702. doi: 10.1007/s00044-012-0379-1.
  • Razmara, R. S., A. Daneshfar, and R. Sahraei. 2010. Solubility of quercetin in water + methanol and water + ethanol from (292.8 to 333.8) K. Journal of Chemical & Engineering Data 55 (9):3934–6. doi: 10.1021/je9010757.
  • Riva, A., M. Ronchi, G. Petrangolini, S. Bosisio, and P. Allegrini. 2019. Improved oral absorption of quercetin from quercetin phytosome (R), a new delivery system based on food grade lecithin. European Journal of Drug Metabolism and Pharmacokinetics 44 (2):169–77. doi: 10.1007/s13318-018-0517-3.
  • Rodriguez-Mateos, A., R. P. Feliciano, A. Boeres, T. Weber, C. N. dos Santos, M. R. Ventura, and C. Heiss. 2016. Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study. Molecular Nutrition & Food Research 60 (10):2130–40. doi: 10.1002/mnfr.201600250.
  • Rohn, S., N. Buchner, G. Driemel, M. Rauser, and L. W. Kroh. 2007. Thermal degradation of onion quercetin glucosides under roasting conditions. Journal of Agricultural and Food Chemistry 55 (4):1568–73. doi: 10.1021/jf063221i.
  • Romaszko, E., W. Wiczkowski, J. Romaszko, J. Honke, and M. K. Piskula. 2014. Exposure of breastfed infants to quercetin after consumption of a single meal rich in quercetin by their mothers. Molecular Nutrition & Food Research 58 (2):221–8. doi: 10.1002/mnfr.201200773.
  • Rubió, L., M. P. Romero, R. Solà, M. J. Motilva, M. N. Clifford, and A. Macià. 2021. Variation in the methylation of caffeoylquinic acids and urinary excretion of 3’-methoxycinnamic acid-4’-sulfate after apple consumption by volunteers. Molecular Nutrition & Food Research 65 (19):e2100471. doi: 10.1002/mnfr.202100471.
  • Ruotolo, R., L. Calani, F. Brighenti, A. Crozier, S. Ottonello, and D. Del Rio. 2014. Glucuronidation does not suppress the estrogenic activity of quercetin in yeast and human breast cancer cell model systems. Archives of Biochemistry and Biophysics 559:62–7. doi: 10.1016/j.abb.2014.03.003.
  • Russell, W. R., S. H. Duncan, L. Scobbie, G. Duncan, L. Cantlay, A. G. Calder, S. E. Anderson, and H. J. Flint. 2013. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Molecular Nutrition & Food Research 57 (3):523–35. doi: 10.1002/mnfr.201200594.
  • Saenger, T., F. Hübner, and H.-U. Humpf. 2017. Short-term biomarkers of apple consumption. Molecular Nutrition & Food Research 61 (3):1600629. doi: 10.1002/mnfr.201600629.
  • Sato, Y., M. Nagata, K. Tetsuka, K. Tamura, A. Miyashita, A. Kawamura, and T. Usui. 2014. Optimized methods for targeted peptide-based quantification of human uridine 5’-diphosphate-glucuronosyltransferases in biological specimens using liquid chromatography-tandem mass spectrometry. Drug Metabolism and Disposition: The Biological Fate of Chemicals 42 (5):885–9. doi: 10.1124/dmd.113.056291.
  • Sawai, Y., K. Kohsaka, Y. Nishiyama, and K. Ando. 1987. Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans. Arzneimittel-Forschung 37:729–32.
  • Schneider, H., A. Schwiertz, M. D. Collins, and M. Blaut. 1999. Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract. Archives of Microbiology 171 (2):81–91. doi: 10.1007/s002030050682.
  • Schulz, H.-U., M. Schürer, D. Bässler, and D. Weiser. 2005. Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittel-Forschung 55 (1):15–22. doi: 10.1055/s-0031-1296820.
  • Sesink, A. L., K. A. O’Leary, and P. C. Hollman. 2001. Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4’-glucoside. The Journal of Nutrition 131 (7):1938–41. doi: 10.1093/jn/131.7.1938.
  • Shi, Y., and G. Williamson. 2015. Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: A randomized, single-blinded, cross-over study. Food & Function 6 (5):1443–8. doi: 10.1039/c5fo00155b.
  • Shi, Y., and G. Williamson. 2016. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: A randomised, double-blinded, placebo-controlled, cross-over trial. The British Journal of Nutrition 115 (5):800–6. doi: 10.1017/S0007114515005310.
  • Shimoi, K., I. Tomita, T. Nakayama, and B. T. Zhu. 2004. Differential biological activity of quercetin-3-sulfate in normal and cancerous human breast cells. Cancer Research 64 (7_Supplement):316–
  • Si, T. L., Q. Liu, Y. F. Ren, H. Li, X. Y. Xu, E. H. Li, S. Y. Pan, J. L. Zhang, and K. X. Wang. 2016. Enhanced anti-inflammatory effects of DHA and quercetin in lipopolysaccharide-induced RAW264.7 macrophages by inhibiting NF-kappaB and MAPK activation. Molecular Medicine Reports 14 (1):499–508. doi: 10.3892/mmr.2016.5259.
  • Simonetti, P., C. Gardana, P. Riso, P. Mauri, P. Pietta, and M. Porrini. 2005. Glycosylated flavonoids from tomato purée are bioavailable in humans. Nutrition Research 25 (8):717–26. doi: 10.1016/j.nutres.2005.05.001.
  • Song, B. J., Z. E. Jouni, and M. G. Ferruzzi. 2013. Assessment of phytochemical content in human milk during different stages of lactation. Nutrition (Burbank, Los Angeles County, Calif.) 29 (1):195–202. doi: 10.1016/j.nut.2012.07.015.
  • Song, J., O. Kwon, S. Chen, R. Daruwala, P. Eck, J. B. Park, and M. Levine. 2002. Flavonoid inhibition of sodium-dependent Vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for Vitamin C and glucose. The Journal of Biological Chemistry 277 (18):15252–60. doi: 10.1074/jbc.M110496200.
  • Spencer, J. P. E., G. G. C. Kuhnle, R. J. Williams, and C. Rice-Evans. 2003. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. The Biochemical Journal 372 (Pt 1):173–81. doi: 10.1042/bj20021972.
  • Srinivas, K., J. W. King, L. R. Howard, and J. K. Monrad. 2010. Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. Journal of Food Engineering 100 (2):208–18. doi: 10.1016/j.jfoodeng.2010.04.001.
  • Storhaug, C. L., S. K. Fosse, and L. T. Fadnes. 2017. Country, regional, and global estimates for lactose malabsorption in adults: A systematic review and meta-analysis. The Lancet. Gastroenterology & Hepatology 2 (10):738–46. doi: 10.1016/s2468-1253(17)30154-1.
  • Suomela, J. P., M. Ahotupa, B. Yang, T. Vasankari, and H. Kallio. 2006. Absorption of flavonols derived from Sea Buckthorn (Hippophae rhamnoides L.) and their effect on emerging risk factors for cardiovascular disease in humans. Journal of Agricultural and Food Chemistry 54 (19):7364–9. doi: 10.1021/jf061889r.
  • Suri, S., M. A. Taylor, A. Verity, S. Tribolo, P. W. Needs, P. A. Kroon, D. A. Hughes, and V. G. Wilson. 2008. A comparative study of the effects of quercetin and its glucuronide and sulfate metabolites on human neutrophil function in vitro. Biochemical Pharmacology 76 (5):645–53. doi: 10.1016/j.bcp.2008.06.010.
  • Suri, S., X. H. Liu, S. Rayment, D. A. Hughes, P. A. Kroon, P. W. Needs, M. A. Taylor, S. Tribolo, and V. G. Wilson. 2010. Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. British Journal of Pharmacology 159 (3):566–75. doi: 10.1111/j.1476-5381.2009.00556.x.
  • Tanaka, S., A. Trakooncharoenvit, M. Nishikawa, S. Ikushiro, and H. Hara. 2019. Comprehensive analyses of quercetin conjugates by LC/MS/MS revealed that isorhamnetin-7-O-glucuronide-4’-O-sulfate is a major metabolite in plasma of rats fed with quercetin glucosides. Journal of Agricultural and Food Chemistry 67 (15):4240–9. doi: 10.1021/acs.jafc.8b06929.
  • Tanaka, S., A. Trakooncharoenvit, M. Nishikawa, S. Ikushiro, and H. Hara. 2022. Heteroconjugates of quercetin with 4’-O-sulfate selectively accumulate in rat plasma due to limited urinary excretion. Food & Function 13 (3):1459–71. doi: 10.1039/d1fo03478b.
  • Tang, J., P. Diao, X. Shu, L. Li, and L. Xiong. 2019. Quercetin and quercitrin attenuates the inflammatory response and oxidative stress in LPS-induced RAW264.7 cells: In vitro assessment and a theoretical model. BioMed Research International 2019:7039802–8. doi: 10.1155/2019/7039802.
  • Tribolo, S., F. Lodi, C. Connor, S. Suri, V. G. Wilson, M. A. Taylor, P. W. Needs, P. A. Kroon, and D. A. Hughes. 2008. Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197 (1):50–6. doi: 10.1016/j.atherosclerosis.2007.07.040.
  • Tribolo, S., F. Lodi, M. S. Winterbone, S. Saha, P. W. Needs, D. A. Hughes, and P. A. Kroon. 2013. Human metabolic transformation of quercetin blocks its capacity to decrease endothelial nitric oxide synthase (eNOS) expression and endothelin-1 secretion by human endothelial cells. Journal of Agricultural and Food Chemistry 61 (36):8589–96. doi: 10.1021/jf402511c.
  • Tsai, C. F., G. W. Chen, Y. C. Chen, C. K. Shen, D. Y. Lu, L. Y. Yang, J. H. Chen, and W. L. Yeh. 2021. Regulatory effects of quercetin on M1/M2 macrophage polarization and oxidative/antioxidative balance. Nutrients 14 (1):67. doi: 10.3390/nu14010067.
  • Tsiara, I., A. Riemer, M. S. P. Correia, A. Rodriguez-Mateos, and D. Globisch. 2023. Immobilized enzymes on magnetic beads for separate mass spectrometric investigation of human phase II metabolite classes. Analytical Chemistry 95 (33):12565–71. doi: 10.1021/acs.anachem.3c02988.
  • Tumova, S., A. Kerimi, and G. Williamson. 2019. Long term treatment with quercetin in contrast to the sulfate and glucuronide conjugates affects HIF1 alpha stability and Nrf2 signaling in endothelial cells and leads to changes in glucose metabolism. Free Radical Biology & Medicine 137:158–68. doi: 10.1016/j.freeradbiomed.2019.04.023.
  • Ulbrich, K., N. Reichardt, A. Braune, L. W. Kroh, M. Blaut, and S. Rohn. 2015. The microbial degradation of onion flavonol glucosides and their roasting products by the human gut bacteria Eubacterium ramulus and Flavonifractor plautii. Food Research International 67:349–55. doi: 10.1016/j.foodres.2014.11.051.
  • Vafeiadou, K., D. Vauzour, A. Rodriguez-Mateos, M. Whiteman, R. J. Williams, and J. P. E. Spencer. 2008. Glial metabolism of quercetin reduces its neurotoxic potential. Archives of Biochemistry and Biophysics 478 (2):195–200. doi: 10.1016/j.abb.2008.07.014.
  • van der Woude, H., G. M. Alink, B. E. J. van Rossum, K. Walle, H. van Steeg, T. Walle, and I. Rietjens. 2005. Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activity. Chemical Research in Toxicology 18 (12):1907–16. doi: 10.1021/tx050201m.
  • van der Woude, H., M. G. Boersma, J. Vervoort, and I. M. C. M. Rietjens. 2004. Identification of 14 quercetin phase II mono- and mixed conjugates and their formation by rat and human phase II in vitro model systems. Chemical Research in Toxicology 17 (11):1520–30. doi: 10.1021/tx049826v.
  • van Zanden, J. J., O. Ben Hamman, M. L. van Iersel, S. Boeren, N. H. Cnubben, M. L. Bello, J. Vervoort, P. J. van Bladeren, and I. M. Rietjens. 2003. Inhibition of human glutathione S-transferase P1-1 by the flavonoid quercetin. Chemico-Biological Interactions 145 (2):139–48. doi: 10.1016/s0009-2797(02)00250-8.
  • Vrhovsek, U., D. Masuero, L. Palmieri, and F. Mattivi. 2012. Identification and quantification of flavonol glycosides in cultivated blueberry cultivars. Journal of Food Composition and Analysis 25 (1):9–16. doi: 10.1016/j.jfca.2011.04.015.
  • Vvedenskaya, I. O., R. T. Rosen, J. E. Guido, D. J. Russell, K. A. Mills, and N. Vorsa. 2004. Characterization of Flavonols in Cranberry (Vaccinium macrocarpon) Powder. Journal of Agricultural and Food Chemistry 52 (2):188–95. doi: 10.1021/jf034970s.
  • Walgren, R. A., J. T. Lin, R. K. Kinne, and T. Walle. 2000. Cellular uptake of dietary flavonoid quercetin 4’-β-glucoside by sodium-dependent glucose transporter SGLT1. J. Pharmacol. Exp. Ther. 294:837–43.
  • Walgren, R. A., K. J. Karnaky, Jr., G. E. Lindenmayer, and T. Walle. 2000. Efflux of dietary flavonoid quercetin 4’-β-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance- associated protein-2. The Journal of Pharmacology and Experimental Therapeutics 294 (3):830–6.
  • Walle, T., T. S. Vincent, and U. K. Walle. 2003. Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells. Biochemical Pharmacology 65 (10):1603–10. doi: 10.1016/s0006-2952(03)00151-5.
  • Walle, T., U. K. Walle, and P. V. Halushka. 2001. Carbon dioxide is the major metabolite of quercetin in humans. The Journal of Nutrition 131 (10):2648–52. doi: 10.1093/jn/131.10.2648.
  • Wang, L. L., Z. C. Zhang, W. Hassan, Y. Li, J. Liu, and J. Shang. 2016. Amelioration of free fatty acid-induced fatty liver by quercetin-3-O-beta-D-glucuronide through modulation of peroxisome proliferator-activated receptor-alpha/sterol regulatory element-binding protein-1c signaling. Hepatology Research: The Official Journal of the Japan Society of Hepatology 46 (2):225–38. doi: 10.1111/hepr.12557.
  • Wang, Y., A. P. Singh, H. N. Nelson, A. J. Kaiser, N. C. Reker, T. L. Hooks, T. Wilson, and N. Vorsa. 2016. Urinary clearance of cranberry flavonol glycosides in humans. Journal of Agricultural and Food Chemistry 64 (42):7931–9. doi: 10.1021/acs.jafc.6b03611.
  • Wiczkowski, W., E. Romaszko, and M. K. Piskula. 2010. Bioavailability of cyanidin glycosides from natural chokeberry (Aronia melanocarpa) juice with dietary-relevant dose of anthocyanins in humans. Journal of Agricultural and Food Chemistry 58 (23):12130–6. doi: 10.1021/jf102979z.
  • Wiczkowski, W., J. Romaszko, A. Bucinski, D. Szawara-Nowak, J. Honke, H. Zielinski, and M. K. Piskula. 2008. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides. The Journal of Nutrition 138 (5):885–8. doi: 10.1093/jn/138.5.885.
  • Williamson, G. 2013. Possible effects of dietary polyphenols on sugar absorption and digestion. Molecular Nutrition & Food Research 57 (1):48–57. doi: 10.1002/mnfr.201200511.
  • Williamson, G., and M. N. Clifford. 2017. Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols. Biochemical Pharmacology 139:24–39. doi: 10.1016/j.bcp.2017.03.012.
  • Williamson, G., C. D. Kay, and A. Crozier. 2018. The bioavailability, transport, and bioactivity of dietary flavonoids: A review from a historical perspective. Comprehensive Reviews in Food Science and Food Safety 17 (5):1054–112. doi: 10.1111/1541-4337.12351.
  • Williamson, G., D. Barron, K. Shimoi, and J. Terao. 2005. In vitro biological properties of flavonoid conjugates found in vivo. Free Radical Research 39 (5):457–69. doi: 10.1080/10715760500053610.
  • Williamson, G., I. Aeberli, L. Miguet, Z. Zhang, M. B. Sanchez, V. Crespy, D. Barron, P. Needs, P. A. Kroon, H. Glavinas, et al. 2007. Interaction of positional isomers of quercetin glucuronides with the transporter ABCC2 (cMOAT, MRP2). Drug Metabolism and Disposition: The Biological Fate of Chemicals 35 (8):1262–8. doi: 10.1124/dmd.106.014241.
  • Winter, J., L. H. Moore, V. R. Dowell, and V. D. Bokkenheuser. 1989. C-ring cleavage of flavonoids by human intestinal bacteria. Applied and Environmental Microbiology 55 (5):1203–8. doi: 10.1128/aem.55.5.1203-1208.1989.
  • Winterbone, M. S., S. Tribolo, P. W. Needs, P. A. Kroon, and D. A. Hughes. 2009. Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202 (2):431–8. doi: 10.1016/j.atherosclerosis.2008.04.040.
  • Wong, C. C., N. P. Botting, C. Orfila, N. Al-Maharik, and G. Williamson. 2011. Flavonoid conjugates interact with organic anion transporters (OATs) and attenuate cytotoxicity of adefovir mediated by organic anion transporter 1 (OAT1/SLC22A6). Biochemical Pharmacology 81 (7):942–9. doi: 10.1016/j.bcp.2011.01.004.
  • Wong, C. C., Y. Akiyama, T. Abe, J. D. Lippiat, C. Orfila, and G. Williamson. 2012. Carrier-mediated transport of quercetin conjugates: Involvement of organic anion transporters and organic anion transporting polypeptides. Biochemical Pharmacology 84 (4):564–70. doi: 10.1016/j.bcp.2012.05.011.
  • Wright, B., L. A. Moraes, C. F. Kemp, W. Mullen, A. Crozier, J. A. Lovegrove, and J. M. Gibbins. 2010. A structural basis for the inhibition of collagen-stimulated platelet function by quercetin and structurally related flavonoids. British Journal of Pharmacology 159 (6):1312–25. doi: 10.1111/j.1476-5381.2009.00632.x.
  • Wu, Q., P. A. Kroon, H. Shao, P. W. Needs, and X. Yang. 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. Journal of Agricultural and Food Chemistry 66 (27):7181–9. doi: 10.1021/acs.jafc.8b02420.
  • Wu, Q., P. W. Needs, Y. Lu, P. A. Kroon, D. Ren, and X. Yang. 2018. Different antitumor effects of quercetin, quercetin-3’-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food & Function 9 (3):1736–46. doi: 10.1039/c7fo01964e.
  • Xu, M., H. Huang, X. Mo, Y. Zhu, X. Chen, X. Li, X. Peng, Z. Xu, L. Chen, S. Rong, et al. 2021. Quercetin-3-O-glucuronide alleviates cognitive deficit and toxicity in A beta(1-42)-induced AD-like mice and SH-SY5Y cells. Molecular Nutrition & Food Research 65 (6):e2000660. doi: 10.1002/mnfr.202000660.
  • Xu, Y., Y. Li, X. Ma, W. Alotaibi, M. Le Sayec, A. Cheok, E. Wood, S. Hein, P. Young Tie Yang, W. L. Hall, et al. 2023. Comparison between dietary assessment methods and biomarkers in estimating dietary (poly)phenol intake. Food & Function 14 (3):1369–86. doi: 10.1039/d2fo02755k.
  • Yamazaki, S., H. Sakakibara, H. Takemura, M. Yasuda, and K. Shimoi. 2014. Quercetin-3-O-glucuronide inhibits noradrenaline binding to α2-adrenergic receptor, thus suppressing DNA damage induced by treatment with 4-hydroxyestradiol and noradrenaline in MCF-10A cells. The Journal of Steroid Biochemistry and Molecular Biology 143:122–9. doi: 10.1016/j.jsbmb.2014.02.014.
  • Yamazaki, S., N. Miyoshi, K. Kawabata, M. Yasuda, and K. Shimoi. 2014. Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of MDA-MB-231 human breast cancer cells by blocking beta(2)-adrenergic signaling. Archives of Biochemistry and Biophysics 557:18–27. doi: 10.1016/j.abb.2014.05.030.
  • Yang, H. H., K. Hwangbo, M. S. Zheng, J. H. Cho, J. K. Son, H. Y. Kim, S. H. Baek, H. C. Choi, S. Y. Park, and J. R. Kim. 2014. Quercetin-3-O-beta-D-glucuronide isolated from polygonum aviculare inhibits cellular senescence in human primary cells. Archives of Pharmacal Research 37 (9):1219–33. doi: 10.1007/s12272-014-0344-2.
  • Yang, Q. Q., Z. R. Wang, X. H. Chen, Z. H. Guo, L. Y. Wen, and J. Q. Kan. 2022. Evaluation of bitter compounds in Zanthoxylum schinifolium Sieb. et Zucc. by instrumental and sensory analyses. Food Chemistry 390:133180. doi: 10.1016/j.foodchem.2022.133180.
  • Yao, Z., Y. Gu, Q. Zhang, L. Liu, G. Meng, H. Wu, Y. Xia, X. Bao, H. Shi, S. Sun, et al. 2019. Estimated daily quercetin intake and association with the prevalence of type 2 diabetes mellitus in Chinese adults. European Journal of Nutrition 58 (2):819–30. doi: 10.1007/s00394-018-1713-2.
  • Yokoyama, A., H. Sakakibara, A. Crozier, Y. Kawai, A. Matsui, J. Terao, S. Kumazawa, and K. Shimoi. 2009. Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats. Free Radical Research 43:913–921.
  • Young, J. F., S. E. Nielsen, J. Haraldsdóttir, B. Daneshvar, S. T. Lauridsen, P. Knuthsen, A. Crozier, B. Sandström, and L. O. Dragsted. 1999. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status. The American Journal of Clinical Nutrition 69 (1):87–94. doi: 10.1093/ajcn/69.1.87.
  • Yuste, S., I. A. Ludwig, L. Rubió, M.-P. Romero, A. Pedret, R.-M. Valls, R. Solà, M.-J. Motilva, and A. Macià. 2019. In vivo biotransformation of (poly)phenols and anthocyanins of red-fleshed apple and identification of intake biomarkers. Journal of Functional Foods 55:146–55. doi: 10.1016/j.jff.2019.02.013.
  • Zenkevich, I. G., and T. I. Pushkareva. 2017. Systematization of the results of the chromatography–mass spectrometry identification of the products of quercetin oxidation by atmospheric oxygen in aqueous solutions. Journal of Analytical Chemistry 72 (10):1061–75. doi: 10.1134/S1061934817080147.
  • Zhou, J.-F., W.-J. Wang, Z.-P. Yin, G.-D. Zheng, J.-G. Chen, J.-E. Li, L.-L. Chen, and Q.-F. Zhang. 2021. Quercetin is a promising pancreatic lipase inhibitor in reducing fat absorption in vivo. Food Bioscience 43:101248. doi: 10.1016/j.fbio.2021.101248.