Abstract

Quercetin is a plant flavonoid phytochemical exhibiting a broad spectrum of properties i.a. antioxidant, anti-inflammatory and immunomodulatory. However, the effect of quercetin is not clear. This compound at low concentrations can stimulate proliferation of human cells, so it can be a potential drug in the treatment of neurodegenerative diseases and in high concentrations, it induces apoptosis thereby eliminating the infected or abnormal cells and can serve as a potential anticancer drug with wide clinical application. Action of quercetin can be explained by its interference with cellular enzymes, receptors, transporters and signalling system. Due to its widespread occurrence in the plant world, it is an integral component of the human diet. The dietary quercetin occurs most often in the form of β-glycosides connected mostly with rutinose, rhamnose and glucose. Depending on the nutritional habits, the daily intake of flavonoids, including quercetin, ranges from 3 to 70 mg. Epidemiological studies confirm an inverse correlation between the consumption of flavonoids and the incidence of lifestyle diseases and tumor formation. Published data indicate that consumption of foods rich in flavonoids reduces the risk of coronary heart disease. Thus, flavonoids – including quercetin – seem to be an interesting pro-health agent.

References

• 1. Almén M.S., Jacobsson J.A., Moschonis G., Benedict C., ChrousosG.P., Fredriksson R., Schiöth H.B.: Genome wide analysis reveals associationof a FTO gene variant with epigenetic changes. Genomics,2012; 99: 132-137
  Google Scholar
• 2. Arita K., Ariyoshi M., Tochio H.: Recognition of hemi-methylatedDnA by the SRA protein UHRF1 by a base-flipping mechanism. Nature,2008; 455: 818-821
  Google Scholar
• 3. Austin R.C., Lentz S.R., Werstuck G.H.: Role of hyperhomocysteinemiain endothelial dysfunction and atherothrombotic disease.Cell Death Differ., 2004; 11: S56-S64
  Google Scholar
• 4. Bell C.G., Finer S., Lindgren C.M., Wilson G.A., Vardhman K. RakyanV.K., Teschendorff A.E., Akan P., Stupka E., Down T.A., ProkopenkoI., Morison I.M., Mill J., Pidsley R. i wsp.: Integrated geneticand epigenetic analysis identifies haplotype-specific methylationin the FTO type 2 diabetes and obesity susceptibility locus. PLoSOne, 2010; 5: e14040 5 Berthoud H.R., Morrison C.: The brain, appetite, and obesity.Annu. Rev. Psychol., 2008; 59: 55-92
  Google Scholar
• 5. formylcytosine and 5 carboxylcytosine: potential implications for activedemethylation of CpG sites. J. Biol. Chem., 2011; 286: 35334-35338
  Google Scholar
• 6. Bestor T.H.: The DNA methyltransferases of mammals. Hum. Mol.Genet., 2000; 9: 2395-2402
  Google Scholar
• 7. Bhutani N., Burns D.M., Blau H.M.: DNA demethylation dynamics.Cell, 2011; 146: 866-872
  Google Scholar
• 8. Bird A.: DNA methylation patterns and epigenetic memory. GenesDev., 2002; 16: 6-21
  Google Scholar
• 9. Branco M.R., Ficz G., Reik W.: Uncovering the role of 5 hydroxymethylcytosinein the epigenome. Nat. Rev. Genet., 2011; 13: 7-13
  Google Scholar
• 10. Campión J., Milagro F.I., Martínez J.A.: Individuality and epigeneticsin obesity. Obes. Rev., 2009; 10: 383-392
  Google Scholar
• 11. Chen C., Visootsak J., Dills S., Graham J.M. Jr.: Prader-Willi syndrome:an update and review for the primary pediatrician. Clin.Pediatr. Phila., 2007; 46: 580-591
  Google Scholar
• 12. Chen T.,. Li E.: Structure and function of eukaryotic DNA methyltransferases.Curr. Top Dev. Biol., 2004; 60: 55-89
  Google Scholar
• 13. Chen Z., Riggs A.D.: DNA methylation and demethylation inmammals. J. Biol. Chem., 2011; 286: 18347-18353
  Google Scholar
• 14. Cheng X., Roberts R.J.: AdoMet-dependent methylation, DNAmethyltransferase and base flipping. Nucleic Acids Res., 2001; 29:3784-3795
  Google Scholar
• 15. Cortellino S., Xu J., Sannai M., Moore R., Caretti E., Cigliano A.,Le Coz M., Devarajan K., Wessels A., Soprano D., Abramowitz L.K.,Bartolomei M.S., Rambow F., Bassi M.R, Bruno T. i wsp.: ThymineDNA glycosylase is essential for active DNA demethylation by linkeddeamination-base excision repair. Cell, 2011; 146: 67-79
  Google Scholar
• 16. Deaton A.M, Bird A.: CpG islands and the regulation of transcription.Genes Dev., 2011; 25: 1010-1022
  Google Scholar
• 17. Dina C., Meyre D., Gallina S., Durand E., Körner A., Jacobson P.,Carlsson L.M., Kiess W., Vatin V., Lecoeur C., Delplanque J., Vaillant E.,Pattou F., Ruiz J., Weill J. i wsp.: Variation in FTO contributes to childhoodobesity and severe adult obesity. Nat. Genet., 2007; 39: 724-726
  Google Scholar
• 18. Dolinoy D.C.: The agouti mouse model: an epigenetic biosensorfor nutritional and environmental alterations on the fetal epigenome.Nutr. Rev., 2008; 66: S7-S11
  Google Scholar
• 19. Dolinoy D.C., Huang D., Jirtle R.L.: Maternal nutrient supplementationcounteracts bisphenol A-induced DNA hypomethylation inearly development. Proc. Natl. Acad. Sci. USA, 2007; 104: 13056-13061
  Google Scholar
• 20. Dolinoy D.C., Weidman J.R., Waterland R.A., Jirtle R.L.: Maternalgenistein alters coat color and protects Avy mouse offspring fromobesity by modifying the fetal epigenome. Environ. Health Perspect.,2006; 114: 567-572
  Google Scholar
• 21. Fawcett K.A., Barroso I.: The genetics of obesity: FTO leads theway. Trends Genet., 2010, 26: 226-274
  Google Scholar
• 22. Finkelstein J.D.: Methionine metabolism in mammals. J. Nutr.Biochem., 1990; 1: 228-237
  Google Scholar
• 23. Frayling T.M., Timpson N.J., Weedon M.N., Zeggini E., Freathy R.M.,Lindgren C.M., Perry J.R., Elliott K.S., Lango H., Rayner N.W., ShieldsB., Harries L.W., Barrett J.C., Ellard S., Groves C.J. i wsp.: A commonvariant in the FTO gene is associated with body mass index and predisposesto childhood and adult obesity. Science, 2007; 316: 889-894
  Google Scholar
• 24. Gąsiorowska D., Korzeniowska K., Jabłecka A.: Homocysteina.Farmacja współczesna, 2008; 1: 169-175
  Google Scholar
• 25. Gehring M., Reik W., Henikoff S.: DNA demethylation by DNArepair. Trends Genet., 2009; 25: 82-90
  Google Scholar
• 26. Germann M.W., Johnson C.N., Spring A.M.: Recognition of damagedDNA: structure and dynamic markers. Med. Res. Rev., 2012;32: 659-683
  Google Scholar
• 27. Goldberg A.D., Allis C.D., Bernstein E.: Epigenetics: a landscapetakes shape. Cell, 2007; 128: 635-638
  Google Scholar
• 28. Gopalakrishnan S., Van Emburgh B.O., Robertson K.D.: DNAmethylation in development and human disease. Mutat. Res., 2008;647: 30-38
  Google Scholar
• 29. Gu T.P., Guo F, Yang H.,Wu H.P., Xu G.F., Liu W., Xie Z.G., Shi L.,He X., Jin S., Iqbal K., Shi Y.g., Deng Z., Szabó P.E., Pfeifer G.P., Li J.,Xu G.L.: The role of Tet3 DNA dioxygenase in epigenetic reprogrammingby oocytes. Nature, 2011; 477: 606-610
  Google Scholar
• 30. Guibert S., Forné T., Weber M.: Global profiling of DNA methylationerasure in mouse primordial germ cells. Genome Res., 2012;22: 633-641
  Google Scholar
• 31. Guo J., Su Y., Zhong C., Ming G.L., Song H.: Hydroxylation of 5methylcytosine by TET1 promotes active DNA demethylation in theadult brain. Cell, 2011; 145: 423-434
  Google Scholar
• 32. Han Z., Niu T., Chang J., Lei X., Zhao M., Wang Q., Cheng W., WangJ., Feng Y., Chai J.: Crystal structure of the FTO protein reveals basisfor its substrate specificity. Nature, 2010; 464: 1205-1209
  Google Scholar
• 33. Hattori N., Abe T., Hattori N., Suzuki M., Matsuyama T., Yoshida S.,Li E., Shiota K.: Preference of DNA methyltransferases for CpG islandsin mouse embryonic stem cells. Genome Res., 2004; 14: 1733-1740
  Google Scholar
• 34. He Y.F., Li B.Z., Li Z., Liu P., Wang Y., Tang Q., Ding J., Jia Y., ChenZ., Li L., Sun Y., Li X., Dai Q., Song C.X., Zhang K., He C., Xu G.L.: Tet–mediated formation of 5- carboxylcytosine and its excision by TDGin mammalian DNA. Science, 2011; 333: 1303-1307
  Google Scholar
• 35. Hendrich B., Hardeland U., Ng H.H., Jiricny J., Bird A.: The thymineglycosylase MBD4 can bind to the product of deamination atmethylated CpG sites. Nature, 1999; 401: 301-304
  Google Scholar
• 36. Hermann A., Gowher H., Jeltsch A.: Biochemistry and biologyof mammalian DNA methyltransferases. Cell. Mol. Life Sci., 2004;61: 2571-2587
  Google Scholar
• 37. Hermann A., Goyal R., Jeltsch A.: The Dnmt1 DNA-(cytosine–C5)-methyltransferase methylates DNA processively with high preferencefor hemimethylated target sites. J. Biol. Chem., 2004; 279:48350-48359
  Google Scholar
• 38. Herrera B.M., Keildson S., Lindgren C.M.: Genetics and epigeneticsof obesity. Maturitas, 2011; 69: 41-49
  Google Scholar
• 39. Hu J.L., Zhou B.O., Zhang R.R., Zhang K.L., Zhou J.Q., Xu G.L.: TheN-terminus of histone H3 is required for de novo DNA methylationin chromatin. Proc. Natl. Acad. Sci. USA, 2009; 106: 22187-22192
  Google Scholar
• 40. Iqbal K., Jin S.G., Pfeifer G.P., Szabó P.E.: Reprogramming of thepaternal genome upon fertilization involves genome-wide oxidationof 5 methylcytosine. Proc. Natl. Acad. Sci. USA, 2011; 108: 3642-3647
  Google Scholar
• 41. Jair K.W., Bachman K.E., Suzuki H., Ting A.H., Rhee I., Yen R.W.,Baylin S.B., Schuebel K.E.: De novo CpG island methylation in humancancer cells. Cancer Res., 2006; 66: 682-692
  Google Scholar
• 42. Jeltsch A.: Molecular enzymology of mammalian DNA methyltransferases.Curr. Top. Microbiol. Immunol., 2006; 301: 203-225
  Google Scholar
• 43. Jia D., Jurkowska R.Z., Zhang X., Jeltsch A., Cheng X.: Structureof Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation.Nature, 2007; 449: 248-251
  Google Scholar
• 44. Jones P.A.: Functions of DNA methylation: islands, start sites,gene bodies and beyond. Nat. Rev. Genet., 2012; 13: 484-492
  Google Scholar
• 45. Karlin S., Burge C.: Dinucleotide relative abundance extremes:a genomic signature. Trends Genet., 1995; 11: 283-290
  Google Scholar
• 46. Kelly T., Yang1 W., Chen C.S., Reynolds K., He J.: Global burdenof obesity in 2005 and projections to 2030. Int. J. Obesity, 2008; 32:1431-1437
  Google Scholar
• 47. Klose R.J., Bird A.P.: Genomic DNA methylation: the mark andits mediators. Trends Biochem. Sci., 2006; 31: 89-97
  Google Scholar
• 48. Kral J.G., Biron S., Simard S., Hould F.S., Lebel S., Marceau S.,Marceau P.: Large maternal weight loss from obesity surgery preventstransmission of obesity to children who were followed for 2to 18 years. Pediatrics, 2006; 118: e1644-e1649
  Google Scholar
• 49. Larder R., Cheung M.K., Tung Y.C., Yeo G.S., Coll A.P.: Where togo with FTO? Trends Endocrinol. Metab. 2011; 22: 53-59
  Google Scholar
• 50. Lei H., Oh S.P., Okano M., Jüttermann R., Goss K.A., Jaenisch R.,Li E.: De novo DNA cytosine methyltransferase activities in mouseembryonic stem cells. Development, 1996; 122: 3195-3205
  Google Scholar
• 51. Li E., Bestor T.H., Jaenisch R.: Targeted mutation of the DNAmethyltransferase gene results in embryonic lethality. Cell, 1992;69: 915-926
  Google Scholar
• 52. Lister R., Pelizzola M., Dowen R.H., Hawkins R.D., Hon G., TontiFilippiniJ., Nery J.R., Lee L., Ye Z., Ngo Q.M., Edsall L., AntosiewiczBourgetJ., Stewart R., Ruotti V., Millar A.H., Thomson J.A., Ren B.,Ecker J.R.: Human DNA methylomes at base resolution show widespreadepigenomic differences. Nature, 2009; 462: 315-322
  Google Scholar
• 53. Maiti A., Drohat A.C.: Thymine DNA glycosylase can rapidly excise
  Google Scholar
• 54. Mato J.M., Alvarez L., Ortiz P., Pajares M.A.: S-adenosylmethioninesynthesis: molecular mechanisms and clinical implications.Pharmacol. Ther., 1997; 73: 265-280
  Google Scholar
• 55. Münzel M., Globisch D., Carell T.: 5-Hydroxymethylcytosine,the sixth base of the genome. Angew. Chem. (Int. Ed. Engl.), 2011;50: 6460-6468
  Google Scholar
• 56. Okano M., Li E.: Genetic analyses of DNA methyltransferasegenes in mouse model system. J. Nutr., 2002; 132: 2462S-2465S
  Google Scholar
• 57. Olszewska M., Kurpisz M.: Metylacja i jej rola regulacyjna wobecrodzicielskiego piętna genomowego. Postępy Hig. Med. Dośw.,2010; 64: 642-649
  Google Scholar
• 58. Ooi S.K., Qiu C., Bernstein E., Li K., Jia D., Yang Z., ErdjumentBromageH., Tempst P., Lin S.P., Allis C.D., Cheng X., Bestor T.H.:DNMT3L connects unmethylated lysine 4 of histone H3 to de novomethylation of DNA. Nature, 2007; 448: 714-717
  Google Scholar
• 59. Pennings S., Allan J., Davey C.S.: DNA methylation, nucleosomeformation and positioning. Brief. Funct. Genomic Proteomic, 2005;3: 351-361
  Google Scholar
• 60. Portela A., Esteller M.: Epigenetic modifications and humandisease. Nature Biotechnol., 2010; 28: 1057-1068
  Google Scholar
• 61. Qiu A., Jansen M., Sakaris A., Min S.H., Chattopadhyay S., Tsai E.,Sandoval C., Zhao R., Akabas M.H., Goldman I.D.: Identification of anintestinal folate transporter and the molecular basis for hereditaryfolate malabsorption. Cell, 2006; 127: 917-928
  Google Scholar
• 62. Rakyan V.K., Blewitt M.E., Druker R., Preis J.I., Whitelaw E.: Metastableepialleles in mammals. Trends Genet., 2002; 18: 348-351
  Google Scholar
• 63. Rivera R.M., Ross J.W.: Epigenetics in fertilization and preimplantationembryo development. Prog. Biophys. Mol. Biol., 2013;113: 423-432
  Google Scholar
• 64. Rubin B.S., Murray M.K., Damassa D.A., King J.C., Soto A.M.:Perinatal exposure to low doses of bisphenol A affects body weight,patterns of estrous cyclicity, and plasma LH levels. Environ. HealthPerspect., 2001; 109: 675-680
  Google Scholar
• 65. Sasaki H., Matsui Y.: Epigenetic events in mammalian germcelldevelopment: reprogramming and beyond. Nat. Rev. Genet.,2008; 9: 129-140
  Google Scholar
• 66. Saxonov S., Berg P., Brutlag DL.: A genome-wide analysis ofCpG dinucleotides in the human genome distinguishes two distinctclasses of promoters. Proc. Natl. Acad. Sci. USA, 2006; 103: 1412-1417
  Google Scholar
• 67. Schär P., Fritsch O.: DNA repair and the control of DNA methylation.Prog. Drug Res., 2011; 67: 51-68
  Google Scholar
• 68. Scuteri A., Sanna S., Chen W.M., Uda M., Albai G., Strait J., NajjarS., Nagaraja R., Orrú M., Usala G., Dei M., Lai S., Maschio A., BusoneroF., Mulas A. et al.: Genome-wide association scan shows genetic variantsin the FTO gene are associated with obesity-related traits. PLoSGenet., 2007; 3: e115
  Google Scholar
• 69. Smith Z.D., Meissner A.: DNA methylation: roles in mammaliandevelopment. Nat. Rev. Genet., 2013; 14: 204-220
  Google Scholar
• 70. Stanger O.: Physiology of folic acid in health and disease. Curr.Drug Metab., 2002; 3: 211-223
  Google Scholar
• 71. Suetake I., Shinozaki F., Miyagawa J., Takeshima H., Tajima S.: DNMT3Lstimulates the DNA methylation activity of Dnmt3a and Dnmt3bthrough a direct interaction. J. Biol. Chem., 2004; 279: 27816-27823
  Google Scholar
• 72. Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., BrudnoY., Agarwal S., Iyer L.M., Liu D.R., Aravind L., Rao A.: Conversion of5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNAby MLL partner TET1. Science, 2009; 324: 930-935
  Google Scholar
• 73. Vucetic Z., Carlin J.L., Totoki K., Reyes T.M.: Epigenetic dysregulationof the dopamine system in diet-induced obesity. J. Neurochem.,2012; 120: 891-898
  Google Scholar
• 74. Vucetic Z., Kimmel J., Reye T.M.: Chronic high-fat diet drivespostnatal epigenetic regulation of μ-opioid receptor in the brain.Neuropsychopharmacology, 2011; 36: 1199-1206
  Google Scholar
• 75. Vucetic Z., Reyes T.M.: Central dopaminergic circruitry controllingfood intake and reward: implcations for the regulation ofobesity. Wiley Interdiscip. Rev. Syst. Biol. Med., 2010; 2: 577-593
  Google Scholar
• 76. Waterland R.A., Travisano M., Tahiliani K.G., Rached M.T., MirzaS.: Methyl donor supplementation prevents transgenerational amplificationof obesity. Int. J. Obes., 2008; 32: 1373-1379
  Google Scholar
• 77. Weber M., Hellmann I., Stadler M.B., Ramos L., Pääbo S., RebhanM., Schübeler D.: Distribution, silencing potential and evolutionaryimpact of promoter DNA methylation in the human genome. Nat.Genet., 2007; 39: 457-466
  Google Scholar
• 78. Weinhold B.: Epigenetics: the science of change. Environ. HealthPerspect., 2006; 114: 160-167
  Google Scholar
• 79. Wossidlo, M., Nakamura T., Lepikhov K., Marques C.J., ZakhartchenkoV., Boiani M., Arand J., Nakano T., Reik W., Walter J.: 5-hydroxymethylcytosine in the mammalian zygote is linked with epigeneticreprogramming. Nat. Commun., 2011; 2: 241
  Google Scholar
• 80. Wu S.C., Zhang Y.: Active DNA demethylation: many roads leadto Rome. Nat. Rev. Mol. Cell Biol., 2010; 11: 607-620
  Google Scholar
• 81. Xu Y., Wu F., Tan L., Xiong L., Deng J., Barbera A.J., Zheng L.,Zhang H., Huang S., Min J., Nicholson T., Chen T., Xu G., Shi Y., ZhangK., Shi Y.G.:Genome-wide regulation of 5hmC, 5mC, and gene expressionby Tet1 hydroxylase in mouse embryonic stem cells. Mol. Cell,2011; 42: 451-464
  Google Scholar
• 82. Yeo G.S., O’Rahilly S.: Uncovering the biology of FTO. Mol. Metab.,2012; 1: 32-36
  Google Scholar
• 83. Yoder J.A., Walsh C.P., Bestor T.H.: Cytosine methylation and theecology of intragenomic parasites. Trends Genet., 1997; 13: 335-340
  Google Scholar
• 84. Youngson N.A., Morris M.J.: What obesity research tells us aboutepigenetic mechanisms. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 2013;368: 1-13
  Google Scholar
• 85. Zhu J.K.: Active DNA demethylation mediated by DNA glycosylases.Annu. Rev. Genet., 2009; 43: 143-166
  Google Scholar
• 86. Ziller M.J., Müller F., Liao J., Zhang Y., Gu H., Bock C., Boyle P.,Epstein C.B., Bernstein B.E., Lengauer T., Gnirke A., Meissner A.: Genomicdistribution and inter-sample variation of non-CpG methylationacross human cell types. PLoS Genet., 2011; 7: e1002389
  Google Scholar

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