The metabolism of anthocyanins

Current Drug Metabolism

Volumn 15, Issue 1, 2014, Pages 3-13

  Hribar, Urša ^a   Ulrih, Nataša Poklar ^a,b  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

^b Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins CipKeBiP   (Slovenia)

Author keywords

Anthocyanins; Bioactivity; Bioavailability; Blood brain barrier; Human serum albumin; Metabolism

Indexed keywords

ANTHOCYANIN; CAFFEIC ACID; CYANIDIN 3 GLUCOSIDE; DELPHINIDIN; FERULIC ACID; GLUCURONIDE; HESPERETIN; KAEMPFEROL; MALVIDIN CHLORIDE; NARINGENIN; PELARGONIDIN; PROTOCATECHUIC ACID; QUERCETIN; VANILLIC ACID;

ANTIOXIDANT ACTIVITY; BINDING AFFINITY; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM DISEASE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DEGRADATION; DRUG HYDROLYSIS; DRUG METABOLISM; DRUG OXIDATION; DRUG PENETRATION; DRUG SOLUBILITY; DRUG TRANSFORMATION; DRUG TRANSPORT; GLYCOSYLATION; HUMAN; NONHUMAN; PROTEIN INTERACTION; REVIEW; STRUCTURE ACTIVITY RELATION;

ANTHOCYANINS; BIOLOGICAL AVAILABILITY; BLOOD PROTEINS; BLOOD-BRAIN BARRIER; HUMANS;

EID: 84896364006     PISSN: 13892002     EISSN: 18755453     Source Type: Journal    
DOI: 10.2174/1389200214666131211160308     Document Type: Review

References (134)

1. Fennema, O. R.; Damodaran, S.; Parkin, K. L. Fennema's food chemistry, 4th ed.; CRC press: Boca Raton, 2008.
2. Horbowicz, M.; Kosson, R.; Grzesiuk, A.; Debski, H. Anthocyanins of fruits and vegetables - their occurrence, analysis and role in human nutrition. Vegetable Crops Res. Bull., 2008, 68, 5-22.
3. Kong, J. M.; Chia, L. S.; Goh, N. K.; Chia, T. F.; Brouillard, R. Analysis and biological activities of anthocyanins. Phytochemistry, 2003, 64, 923-933.
4. Khknen, M. P.; Heinonen, M. Antioxidant activity of anthocyanins and their aglycones. Agric. Food Chem., 2003, 51, 628-633.
5. Clifford, M. N. Anthocyanins - nature, occurrence and dietary burden. J. Sci. Food Agric., 2000, 80, 1063-1072.
6. Andersen, O. M.; Jordheim, M. Anthocyanins. In: Encyclopedia of life sciences; John Wiley & Sons Ltd, Chichester, 2010.
7. Mazza, G.; Miniati, E. Anthocyanins in fruits, vegetables and grains. CRC Press, Boca Raton, 1993.
8. Castañeda-Ovando, A.; Pacheco-Hernández, M. L.; Páez-Hernández, M. E.; Rodríguez, J. A.; Galán-Vidal, C. A. Chemical studies of anthocyanins: a review. Food Chem., 2009, 113, 859-871.
9. da Costa, C. T.; Horton, D.; Margolis, S. A. Analysis of anthocyanins in foods by liquid chromatography, liquid chromatographymass spectrometry and capillary electrophoresis. J. Chromatogr. A, 2000, 881, 403-410.
10. Furtado, P.; Figueriredo, P.; das Neves, H. C.; Pina, F. Photochemical and thermal degradation of anthocyanidins. J. Photochem. Photoblol. A, 1993, 75, 113-118.
11. Asen, S.; Stewart, R. N.; Norris, K. H. Co-pigmentation of anthocyanins in plant tissues and its effect on color. Phytochemistry, 1972, 11, 1139-1144.
12. Azevado, J.; Fernandes, I.; Faria, A.; Oliveira, J.; Fernandes, A.; de Freitas, V.; Mateus, N. Antioxidant properties of anthocyanidins, anthocyanidin-3-glucosides and respective portisins. Food Chem., 2010, 119, 518-523.
13. Wu, X.; Beecher, G. R.; Haytowitz, D. B., Gebhardt, S. E.; Prior, R. L. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J. Agric. Food Chem., 2006, 54, 4069-4075.
14. Xu, Y.; Simon, J. E.; Ferruzzi, M. G.; Ho, L.; Pasinetti, G. M.; Wu, Q. Quantification of anthocyanidins in the grapes and grape juice products with acid assisted hydrolysis using LC/MS. J. Funct. Foods, 2012, 4, 710-717.
15. Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79, 727-747.
16. Linseisen, J.; Radtke, J.; Wolfram, G. Flavonoid intake of adults in a Bavarian subgroup of the national food consumption survey. Z. Ernahrungswiss, 1997, 36, 403-412.
17. Ghosh, D.; Konishi, T. Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac. J. Clin. Nutr., 2007, 16, 200-208.
18. Cohen-Boulakia, F.; Valensi, P. E.; Boulahdour, H.; Lestrade, R.; Dufour-Lamartinie, J. F.; Hort-Legrand, C.; Abraham, B. In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides. Metab., 2000, 49, 880-885.
19. Jing, P.; Bomser, J. A.; Schwartz, S. J.; He, J.; Magnuson, B. A.; Giusti, M. M. Structure-function relationships of anthocyanins from various anthocyanin-rich extracts on the inhibition of colon cancer cell growth. J. Agric. Food Chem., 2008, 56, 9391-9398.
20. Kausar, H.; Jeyabalan, J.; Aquil, F.; Chabba, D.; Sidana, J.; Singh, I. P.; Gupta, R. C. Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells. Cancer Lett., 2012, 325, 54-62.
21. Zhang, Y.; Vareed, S. K.; Nair, M. G. Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sci., 2005, 76, 1465-1472.
22. Joseph, J. A.; Shukitt-Hale, B.; Denisova, N. A.; Bielinski, D.; Martin, A.; McEwen, J. J.; Bickford, P. C. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J. Neurosci., 1999, 19, 8114-8121.
23. Kim, J. M.; Kim, K. M.; Park, E. H.; Seo, J. H.; Song, J. Y.; Shin, S. C.; Kang, H. L.; Lee, W. K.; Cho, M. J.; Rhee, K. H.; Youn, H. S.; Baik, S. C. Anthocyanins from black soybean inhibit Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells. Microbiol. Immunol., 2013, 57, 366-373.
24. Nohynek, L. J.; Alakomi, H. L.; Kähkönen, M. P.; Heinonen, M.; Helander, I. M.; Oksman-Caldentey, K. M.; Puupponen-Pimia, R. H. Berry phenolics: antimicrobial properties and mechanisms of action against severe human pathogens. Nutr. Cancer, 2006, 54, 18-32.
25. Gaziano, J. M.; Buring, J. E.; Breslow, J. L.; Goldhaber, S. Z.; Rosner, B.; VanDenburgh, M.; Willet, W.; Hennekens, C. H. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N. England J. Med., 1993, 329, 1829-1834.
26. Klatsky, A. L. Epidemiology of coronary heart disease influence of alcohol. Alcohol. Clin. Exp. Res., 1994, 18, 88-96.
27. Elwood, P. C.; Renaud, S.; Sharp, D. S.; Beswick, A. D.; O'Brien, J. R.; Yarnell, J. W. G. Ischemic heart disease and platelet aggregation. Circulation, 1991, 83, 38-44.
28. Wallace, T. C. Anthocyanins in cardiovascular disease. Adv. Nutr., 2011, 2, 1-7.
29. Xiao, J.; Ni, X.; Kai, G.; Chen, X. A review on structure-activity relationship of dietary polyphenols inhibiting α-amylase. Crit. Rev. Food Sci. Nutr., 2013, 53, 497-506.
30. Xiao, J.; Kai, G.; Yamamoto, K.; Chen, X. Advance in dietary polyphenols as α-glucosidases inhibitors: A review on structureactivity relationship aspect. Crit. Rev. Food Sci. Nutr., 2013, 53, 818-836.
31. Selma, M. V.; Espin, J. C.; Tomas-Barberan, F. A. Interaction between phenolics and gut microbiota: role in human health. J. Agric. Food Chem., 2009, 57, 6485-6501.
32. McGhie, T. K.; Walton, M. C.; The bioavailability and absorption of anthocyanins: Towards a better understanding. Mol. Nutr. Food Res., 2007, 51, 702-713.
33. McDougall, G. J.; Fyffe, S.; Dobson, P.; Stewart, D. Anthocyanins from red wine - their stability under simulated gastrointestinal digestion. Phytochemistry, 2005, 66, 2540-2548.
34. McDougall, G. J.; Dobson, P.; Smith, P.; Blake, A.; Stewart, D. Assessing potential bioavailability of raspberry anthocyanins using an in-vitro digestion system. J. Agric. Food Chem., 2005, 53, 5896-5904.
35. He, J.; Wallace, T. C.; Keatley, K. E.; Failla, M. L.; Giusti, M. M. Stability of black raspberry anthocyanins in the digestive tract lumen and transport efficiency into gastric and small intestinal tissues in the rat. J. Agric. Food Chem., 2009, 57, 3141-3148.
36. Tsuda, T.; Horio, F.; Osawa, T. Absorption and metabolism of cyanidin 3-O-β -D-glucoside in rats. FEBS Lett., 1999, 449, 179-182.
37. Vanzo, A.; Terdoslavich, M.; Brandoni, A.; Torres, A. M.; Vrhovšek, U.; Passamonti, S. Uptake of grape anthocyanins into the rat kidney and the involvement of bilitranslocase. Mol. Nutr. Food Res., 2008, 52, 1106-1116.
38. Passamonti, S.; Vrhovsek, U.; Vanzo, A.; Mattivi, F. The stomach as a site for anthocyanins absorption from food. FEBS Lett., 2003, 544, 210-213.
39. Talavéra, S.; Felgines, C.; Texier, O.; Besson, C.; Manach, C., Lamaison J. J.; Rémésy, C. Anthocyanins are efficiently absorbed from the small intestine in rats. J. Nutr., 2004, 134, 2275-2279.
40. Talavéra, S.; Felgines, C.; Texier, O.; Besson, C.; Lamaison, J. L.; Rémésy, C. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. J. Nutr., 2003, 133, 4178-4182.
41. Matsumoto, H.; Inabam, H.; Kishi, M.; Tominaga, S.; Hirayama, M.; Tsuda, T. Orally administered delphinidin-3-rutinoside and cyanidin-3- rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. J. Agric. Food Chem., 2001, 49, 1546-1551.
42. Wu, X.; Cao, G.; Prior, R. L. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J. Nutr., 2002, 132, 1865-1871.
43. Elias, M. M.; Lunazzi, G. C.; Passamonti, S.; Gazzin, B.; Miccio, M.; Stanta, G.; Sottocasa, G. L.; Tribelli, C. Bilitranslocase localization and function in basolateral plasma membrane of renal proximal tubule in rat. Am. J. Physiol., 1990, 259, 559-564.
44. Passamonti, S.; Vrhovsek, U.; Mattivi, F. The interaction of anthocyanins with bilitranslocase. Biochem. Biophys. Res. Commun., 2002, 296, 631-636.
45. Ávila, M.; Hidalgo, M.; Sánchez-Moreno, C.; Pelaez, C.; Requena, T., de Pascual-Teresa, S. Bioconversion of anthocyanin glycosides by Bifidobacteria and Lactobacillus. Food Res. Int., 2009, 42, 1453-1461.
46. Fleschhut, J.; Kratzer, F.; Rechkemmer, G.; Kulling, S. E. Stability and biotransformation of various dietary anthocyanins in vitro. Eur. J. Nutr., 2006, 45, 7-18.
47. Forester, S. C.; Waterhouse, A. L. Identification of cabernet sauvignon anthocyanin gut microflora metabolites. J. Agric. Food Chem., 2008, 56, 9299-9304.
48. Kay, C. D. Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans. Nutr. Res. Rev., 2006, 19, 137-146.
49. Vitaglione, P.; Donnarumma, G.; Napolitano, A.; Galvano, F.; Gallo, A.; Scalfi, L.; Fogliano, V. Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J. Nutr. 2007, 137, 2043-2048.
50. Keppler, K.; Humpf, H. U. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg. Med. Chem., 2005, 13, 5195-5205.
51. Aura, A. M.; Martin-Lopez, P.; O'Leary, K. A.; Williamson, G.; Oksman-Caldentey, K. M.: Poutanen, K.: Santos-Buelga, C. Invitro metabolism of anthocyanins by human gut microflora. Eur. J. Nutr., 2005, 44,133-142.
52. Aura, A. M. Microbial metabolism of dietary phenolic compounds in the colon. Phytochem. Rev., 2008, 7, 407-429.
53. Riso, P.; Visioli, F.; Gardana, C.; Grande, S.; Brusamolino, A.; Galvano, F.; Galvano, G.; Porcini, M. Effects of blood orange juice intake on antioxidant bioavailability and on different markers related to oxidative stress. J. Agric. Food. Chem., 2005, 53, 941-947.
54. Day, A. J.; Cañada, F. J.; Díaz, J. C.; Kroon, P. A.; McLauchlan, R.; Faulds, C. B.; Plumb, G. W.; Morgan, M. R. A.; Williamson, G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase-phlorizin-hydrolase. FEBS Lett., 2000, 468, 166-170.
55. Németh, K.; Plumb, G. W.; Berrin, G. J.; Juge, N.; Jacob, R.; Naim, H. Y.; Williamson, G.; Swallow, D. M.; Kroon P. A. Deglycosylation by small intestinal epithelial cell β-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur. J. Nutr., 2003, 42, 29-42.
56. Faria, A.; Pestana, D.; Azevedo, J.; Martel, F.; de Freitas, V.; Azevedo, I.; Mateus, N.; Calhau, C. Absorption of anthocyanins through intestinal epithelial cells - putative involvement of GLUT2. Mol. Nutr. Food Res., 2009, 53, 1-8.
57. Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr., 2005, 81, 230-242.
58. Felgines, C.; Talavera, S.; Texier, O.; Besson, C.; Fogliano, V.; Lamaison, J. L.; Ia, F. L.; Galvano, G.; Rémésy, C.; Galvano, F. Absorption and metabolism of red orange juice anthocyanins in rats. Br. J. Nutr., 2006, 95, 898-904.
59. Mülleder, U.; Murkovic, M.; Pfannhauser, W. Urinary excretion of cyanidin glucosides. J. Biochem. Biophys. Methods, 2002, 53, 61-66.
60. Wolffram, S.; Block, M.; Ader, P. Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine. J. Nutr., 2002, 132, 630-635.
61. Walton, M. C.; McGhie, T. K.; Reynolds, G. W.; Hendriks, W. H. The flavonol quercetin-3-glucoside inhibits cyanidin-3-glucoside absorption in vitro. J. Agric. Food Chem., 2006, 13, 4913-4920.
62. Felgines, C.; Texier, O.; Besson, C.; Vitaglione, P.; Lamaison, J. L.; Fogliano, V.; Scalbert, A.; Vanella, L.; Galvano, F. Influence of glucose on cyanidin 3-glucoside absorption in rats. Mol. Nutr. Food Res., 2008, 52, 959-964.
63. Bokkenheuser, V. D.; Shackleton, C. H.; Winter, J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal bacteroides from humans. Biochem. J., 1987, 248, 953-956.
64. Aura, A. M.; O'Leary, K. A.: Williamson, G.; Ojala, M.; Bailey, M.; Puupponen-Pimiä, R.; Nuutila, A. M.; Oksman-Caldentey, K. M.; Poutanen, K. Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J. Agric. Food Chem., 2002, 50, 1725-1730.
65. Blaut, M.; Clavel, T. Metabolic diversity of the intestinal microbiota: implications for health and disease. J. Nutr., 2007, 137, 751-755.
66. Spencer, M.; Cai, Y.; Martin, R.; Gaffney, S. H.; Goulding, P. N.; Magnolato, D.; Lilley, T. H.; Haslam, E. Polyphenol complexation - some thoughts and observations. Phytochemistry, 1988, 27, 2397-2409.
67. Kay, C. D.; Kroon, P. A.; Cassidy, A. The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol. Nutr. Food. Res., 2009, 53, 92-101.
68. Galvano, F. Protocatechuic acid: The missing human cyanidins' metabolite. Mol. Nutr. Food Res., 2008, 52, 386-387.
69. Kern, S. M.; Bennet, R. N.; Needs, P. W.; Mellon, F. A.; Kroon, P. A.; Garcia-Conesa, M. T. Characterization of metabolites of hydroxycinnamates in the in-vitro model of human small intestinal epithelium Caco-2 cells. J. Agric. Food Chem., 2003, 51, 7884-7891.
70. Sabolovic, N.; Magdalou, J.; Netter, P.; Abid, A. Nonsteroidal antiinflammatory drugs and phenols glucuronidation in Caco-2 cells - identification of the UDP-glucuronosyltransferases UGT1A6, 1A3 and 2B7. Life Sci., 1994, 67, 185-196.
71. Ng, S. P.; Wong, K. Y.; Zhang, L.; Zuo, Z.; Lin, G. Evaluation of the first-pass glucuronidation of selected flavones in gut by Caco-2 monolayer model. J. Pharm. Pharm. Sci., 2004, 8, 1-9.
72. Ichiyanagi, T.; Shida, Y.; Rahman, M. M.; Hatano, Y.; Konishi, T. Extended glucuronidation is another major path of cyanidin 3-O-β- D-glucopyranoside metabolism in rats. J. Agric. Food Chem., 2005, 53, 7312-7319.
73. Grompe, M.; Pieretti, M.; Caskey C. T.; Ballabio, A. The sulfatase gene family: cross-species PCR cloning using the MOPAC technique. Genomics, 1992, 12, 755-60.
74. Borghoff, S. J.; Birnbaum, L. S. Age-related changes in glucuronidation and deglucuronidation in liver, small intestine, lung, and kidney of male Fischer rats. Drug Metab. Dispos., 1985, 13, 62-67.
75. Kim, D. H.; Yoon, H. K.; Koizumi, M.; Kobashi, K. Sulfation of phenolic antibiotics by sulfotransferase obtained from human intestinal bacterium. Chem. Phar. Bull., 1992, 40, 1056-1057.
76. Runge-Morris, M. A. Regulation of expression of the rodent cytosolic sulfotransferases. FASEB J., 1997, 11, 109-117.
77. Felgines, C.; Talavéra, S.; Gonthier, M. P.; Texier, O.; Scalbert, A.; Lamaison, J. L.; Rémésy, C. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J. Nutr., 2003, 133, 1296-1301.
78. Felgines, C.; Talavéra, S.; Texier, O.; Gil-Izquierdo, A.; Lamaison, J. L.; Rémésy, C. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. J. Agric. Food Chem., 2005, 53, 7721-7727.
79. Hassimotto, N. M. A.; Genovese, M. I.; Lajolo, F. M. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from wild mulberry (Morus nigra L.) in rats. Nutr. Res., 2008, 28, 198-207.
80. Ichiyanagi, T.; Shida, Y.; Rahman, M. M.; Hatano, Y.; Matsumoto, H.; Hirayama, M.; Konishi, T. Metabolic pathway of cyanidin 3-O-β - D-glucopyranoside in rats. J. Agric. Food Chem., 2005, 53, 145-150.
81. Talavéra, S.; Felgines, C.; Texier, O.; Besson, C.; Gil-Izquierdo, A.; Lamaison, J. L.; Rémésy, C. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J. Agric. Food Chem., 2005, 53, 3902-3908.
82. El Mohsen, M. A.; Marks, J.; Kuhnle, G.; Moore, K.; Debnam, E.; Kaila Srai, S.; Rice-Evans, C.; Spencer J. P. E. Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br. J. Nutr., 2006, 95, 51-58.
83. Woodward, G. M.; Needs, P. W.; Kay, C. D. Anthocyanin-derived phenolic acids form glucuronides following simulated gastrointestinal digestion and microsomal glucuronidation. Mol. Nutr. Food Res., 2011, 55, 378-386.
84. Miyazawa, T.; Nakagawa, K.; Kudo, M.; Muraishi, K.; Someya, K. Direct intestinal absorption of red fruit anthocyanins, cyanidin-3- glucoside and cyanidin-3,5-diglucoside, into rats and humans. J. Agric. Food Chem., 1999, 47, 1083-1091.
85. Ichiyanagi, T.; Rahman, M. M.; Kashiwada, Y.; Ikeshiro, Y.; Shida, Y.; Hatano, Y.; Matsumoto, H.; Hirayama M.; Tsuda, T.; Konishi, T. Absorption and metabolism of delphinidin 3-O-β-glucopyranoside in rats. Free Radical. Bio. Med., 2004, 36, 930-937.
86. Vanzo, A.; Vrhovsek, U.; Tramer, F.; Mattivi, F.; Passamonti, S. Exceptionally fast uptake and metabolism of cyanidin-3-glucoside by rat kidneys and liver. J. Nat. Prod., 2011, 74, 1049-1054.
87. Kay, C. D.; Mazza, G.; Holub, B. J.; Wang, J. Anthocyanin metabolites in human urine and serum. Br. J. Nutr., 2004, 91, 933-942.
88. Passamonti, S.; Terdoslavich, M.; Franca, R.; Vanzo, A.; Tramer, F.; Braidot, E.; Petrussa, E., Vianelo, A. Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr. Drug Metab., 2009, 10, 369-394.
89. Maestro, A.; Terdoslavich, M.; Vanzo, A.; Kuku, A.; Tramer, F.; Nicolin, V.; Micali, F.; Decorti, G.; Passamonti, S. Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter. Cardiovasc. Res., 2010, 85, 175-183.
90. Zhu, B. T. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: Importance in pathophysiology and pathogenesis. Curr. Drug Metab., 2002, 3, 321-349.
91. Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. Supplement: Chocolate: Modern science investigates an ancient medicine. J. Nutr., 2000, 130, 2073-2085.
92. Prior, R. L.; Wu, X. Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activity. Free Radical Res., 2006, 40, 1014-1028.
93. Fasano, M.; Curry, S.; Terreno, E.; Galliano, M.; Fanali, G.; Narciso, P.; Notari, S.; Ascezni, P. The extraordinary ligand binding properties of human serum albumin. IUBMB Life, 2005, 57, 787-796.
94. Xiao, J.; Kay G. A review of dietary polyphenol-plasma protein interactions: characterization, influence on the bioactivity, and structure-affinity relationship. Crit. Rev. Food Sci. Nutr., 2012, 52, 85-101.
95. Passamonti, S.; Vrhovsek, U.; Vanzo, A.; Mattivi, F. Fast access of some grape pigments to the brain. J. Agric. Food Chem., 2005, 53, 7029-7034.
96. He, X. M.; Carter, D. C. Atomic structure and chemistry of human serum protein. Nature, 1992, 358, 209-215.
97. Peters, T. All About Albumin Biochemistry, Genetics and Medical Applications. Academic Press: San Diego, 1996.
98. Siemiarczuk, A.; Petersen, C. E.; Ha, C. E.; Yang, J.; Bhagavan, N. V. Analysis of tryptophan fluorescence lifetimes in a series of human serum albumin mutants with substitutions in subdomain 2A. Cell. Biochem. Biophys., 2004, 40, 115-122.
99. Wiese, S.; Gärtner, S.; Rawel, H. M.; Winterhalter, P.; Kulling, S. E. Protein interactions with cyanidin-3-glucoside and its influence on α-amylase activity. J. Sci. Food Agric., 2009, 89, 33-40.
100. Cahyana, Y.; Gordon, M. H. Interaction of anthocyanins with human serum albumin: Influence of pH and chemical structure on binding. Food Chem., 2013, 141, 2278-2285.
101. Matei, I.; Hillebrand, M. Interaction of kaempferol with human serum albumin: A fluorescence and circular dichroism study. J. Pharm. Biomed. Anal., 2010, 51, 768-773.
102. Kraghhansen, U. Structure and ligand-binding properties of human serum albumin. Dan. Med. Bull., 1990, 37, 57-84.
103. Lardner, A. The effects of extracellular pH on immune function. J. Leukocyte Biol., 2001, 69, 522-530.
104. Walle, T. Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorption. Mol. Pharmaceut., 2007, 4, 826-832.
105. Wen, X.; Walle, T. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability. Drug Metab. Dispos., 2006, 34, 1786-1792.
106. Cheema, M. A.; Taboada, P.; Barbosa, S.; Castro, E.; Siddiq, M.; Mosquera, V. Energetics and conformational changes upon complexation of a phenothiazine drug with human serum albumin. Biomacromolecules, 2007, 8, 2576-2585.
107. Xiao, J. B.; Cao, H.; Wang, Y. F.; Zhao, J. Y.; Wei, X. L. Glycosylation of dietary flavonoids decreases the affinities for plasma protein. J. Agric. Food Chem., 2009, 57, 6642-6648.
108. Xiao, J. B.; Cao, H.; Wang, Y. F.; Yamamoto, K.; Wei, X. L. Structure-affinity relationship of flavones on binding to serum albumins: effect of hydroxyl groups on ring A. Mol. Nutr. Food Res., 2010, 54, 253-260.
109. Kurlbaum, M.; Högger, P. Plasma protein binding of polyphenols from maritime pine bark extract (USP). J. Pharm. Biomed. Anal., 2011, 54, 127-132.
110. Bartolomé, B.; Estrella, I.; Hernández, M. T. Interaction of low molecular weight phenolics with proteins (BSA). J. Food Sci., 2000, 65, 617-621.
111. Kanakis, C. D.; Tarantilis, P. A.; Polissiou, M. G.; Diamantoglou, S.; Tajmir-Riahi, H. A. Antioxidant flavonoids bind human serum albumin. J. Mol. Struct., 2006, 798, 69-74.
112. Nozaki, A.; Kimura, T.; Ito, H.; Hatano, T. Interaction of polyphenolic metabolites with human serum albumin: A circular dichroism study. Chem. Pharm. Bull., 2009, 57, 1019-1023.
113. Tsuda, T.; Ueno, Y.; Yoshikawa, T.; Kojo, H.; Osawa, T. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem. Pharmacol., 2006, 71, 1184-1197.
114. Olanow, C. W. An introduction to the free radical hypotesis in Parkinson's disease. Ann. Neurol., 1992, 32, 2-9.
115. Joseph J. A.; Villalobos-Molina, R.; Denisova, N.; Erat, S.; Cutler, R.; Strain, J. G. Age differences in sensitivity to H2O2- or NOinduced reductions in K+-evoked dopamine release from superfused striatal slices: reversals by PBN or Trolox. Free Radic Biol Med., 1996, 20, 821-830.
116. Andres-Lacueva, C.; Shukitt-Hale, B.; Galli, R. L.; Jauregui, O.; Lamuela-Raventos, R. M.; Joseph, J. A. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr. Neurosci., 2005, 8, 111-120.
117. Chen, G.; Luo, J. Anthocyanins: are they beneficial in treating ethanol neurotoxicity? Neurotox Res., 2010, 17, 91-101.
118. Ke, Z.; Liu, Y.; Wang, X.; Fan, Z.; Chen, G.; Xu, M.; Bower, K. A.; Frank, J. A.; Ou, X.; Shi, X.; Luo, J. Cyanidin-3-glucoside ameliorates ethanol neurotoxicity in the developing brain. J. Neurosci. Res., 2011, 89, 1676-1684.
119. Bleich. S.; Spilker, K.; Kurth, C.; Degner, D.; Quintela-Schneider, M.; Javaheripour, K.; Ruther, E.; Kornhuber, J.; Wiltfang, J. Oxidative stress and an altered methionine metabolism in alcoholism. Neurosci. Lett., 2000, 293, 171-174.
120. Bondy, S. C. Ethanol toxicity and oxidative stress. Toxicol. Lett., 1992, 63, 231-241.
121. Haorah, J.; Ramirez, S. H.; Floreani, N.; Gorantla, S.; Morsey, B.; Persidsky, Y.; Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radic. Biol. Med., 2008, 45, 1542-1550.
122. Chen, G.; Bower, K. A.; Xu, M.; Ding, M.; Shi, X.; Ke, Z. J.; Luo, J. Cyanidin-3-glucoside reverses ethanol-induced inhibition of neurite outgrowth: role of glycogen synthase kinase 3β. Neurotox. Res., 2009, 15, 321-331.
123. Tarozzi, A.; Morroni, F.; Merlicco, A.; Bolondi, C.; Teti, G.; Falconi, M.; Cantelli-Forti, G.; Hrelia, P. Neuroprotective effects of cyanidin-3-O-glucopyranoside on amyloid β?(25-35) oligomerinduced toxicity. Neurosci. Lett., 2010, 473, 72-76.
124. Joseph, J. A.; Dalton, T. K.; Hunt, W. A. Age-related decrements in the muscarinic enhancement of K+-evoked release of endogenous striatal dopamine: an indicator of altered cholinergic-dopaminergic reciprocal inhibitory control in senescence. Brain Res., 1988, 454, 140-148.
125. Youdim, K. A.; Dobbie, M. S.; Kuhnle, G.; Proteggente, A. R.; Abbott, N. J.; Rice-Evans, C. Interaction between flavonoids and the blood-brain barrier: in-vitro studies. J. Neurochem., 2003, 85, 180-192.
126. Milbury, P. E.; Kalt, W.; Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier. J. Agric. Food Chem., 2010, 58, 3950-3956.
127. Youdim, K. A.; Hale, B. S.; Joseph, J. A. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med., 2004, 37, 1683-1693.
128. Kalt, W.; Blumberg, J. B.; McDonald, J. E.; Vinqvist-Tymchuk, M. R.; Fillmore, S. A. E.; Graf, B. A.; O'Leary, J. M.; Milbury, P. E. Identification of anthocyanins in the liver, eye, and brain of blueberry- fed pigs. J. Agric. Food Chem., 2008, 56, 705-712.
129. Begley, D. J. Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol. Ther., 2004, 104, 29-45.
130. Dreiseitel, A.; Korte, G.; Schreier, P.; Oehme, A.; Locher, S.; Domani, M.; Hajak, G.; Sand, Presledek P. G. Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B. Pharmacol. Res., 2009, 59, 306-311.
131. Borges, G.; Roowi, S.; Rouanet, J. M.; Duthie, G. G.; Lean, M. E. J.; Crozier, A. The bioavailability of raspberry anthocyanins and ellagitannins in rats. Mol. Nutr. Food Res., 2007, 51, 714-725.
132. Battiston, L.; Macagno, A.; Passamonti, S.; Micali, F.; Sottocasa, G. L. Specific sequence-directed anti-bilitranslocase antibodies as a tool to detect potentially bilirubin-binding proteins in different tissues of the rat. FEBS Lett., 1999, 453, 351-355.
133. Battaglia, E.; Gollan, J. A unique multifunctional transporter translocates estradiol-17-β-glucuronide in rat liver microsomal vesicles. J. Biol. Chem., 2001, 276, 23492-23498.
134. Begley, D. J. Efflux mechanisms in the central nervous system: a powerful influence on drug distribution within the brain. In: Bloodspinal cord and brain barriers in health and disease. Sharma, S. H.; Westman, J., Eds. Elsevier Science; Amsterdam, 2004, 83-97.