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Isoflavones: Chemistry, Analysis, Functions and Effects on Health and Cancer

  • Ko, Kwang-Pil (Department of Preventive Medicine, Gachon University Graduate School of Medicine)
  • Published : 2014.09.15

Abstract

Isoflavones are phytoestrogens and natural plant compounds which are similar to 17-${\beta}$-estradiol in chemical structure. It is known that they can act as estrogen agonists or antagonists, depending on endocrine estrogenic levels, but actions of isoflavones are rather complex due to large number of variables such as chemical structures and mechanisms. Some hypotheses on biological mechanisms have not satisfactorily been confirmed to date and human epidemiological and experimental studies have been relatively limited. Nevertheless, isoflavones and isoflavone rich foods have become a focus onf interest due to positive health benefits on many diseases, especially prevention of hormone-related cancers, cardiovascular disease, osteoporosis, and adverse postmenopausal symptoms, and improvement of physiological condition such as maintaining cognitive function. This review provides an overview of chemistry, analytical techniques (focused on human biospecimens), functions including biological mechanisms, and effects of isoflavones, on the basis of the available meta-analysis and review articles and some original articles, on health and cancer.

Keywords

Isoflavone;chemistry;quantification;health effect;cancer-prevention

References

  1. Adlercreutz H, Bannwart C, Wahala K, et al (1993). Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J Steroid Biochem Mol Biol, 44, 147-53. https://doi.org/10.1016/0960-0760(93)90022-O
  2. Adlercreutz H, Hockerstedt K, Bannwart C, et al (1987). Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG). J Steroid Biochem, 27, 1135-44. https://doi.org/10.1016/0022-4731(87)90200-7
  3. Arora A, Nair MG, Strasburg GM (1998). Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys, 356, 133-41. https://doi.org/10.1006/abbi.1998.0783
  4. Atmaca A, Kleerekoper M, Bayraktar M, et al (2008). Soy isoflavones in the management of postmenopausal osteoporosis. Menopause, 15, 748-57. https://doi.org/10.1097/gme.0b013e31815c1e7f
  5. Barnes S (2010). The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphat Res Biol, 8, 89-98. https://doi.org/10.1089/lrb.2009.0030
  6. Berrino F, Bellati C, Secreto G, et al (2001). Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev, 10, 25-33.
  7. Bolanos R, Del Castillo A, Francia J (2010). Soy isoflavones versus placebo in the treatment of climacteric vasomotor symptoms: systematic review and meta-analysis. Menopause, 17, 660-6.
  8. Breinholt V, Larsen JC (1998). Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay. Chem Res Toxicol, 11, 622-9. https://doi.org/10.1021/tx970170y
  9. Cano A, Garcia-Perez MA, Tarin JJ (2010). Isoflavones and cardiovascular disease. Maturitas, 67, 219-26. https://doi.org/10.1016/j.maturitas.2010.07.015
  10. Cassidy A, Bingham S, Setchell KD (1994). Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr, 60, 333-40.
  11. Cederroth CR, Nef S (2009). Soy, phytoestrogens and metabolism: a review. Mol Cell Endocrinol, 304, 30-42. https://doi.org/10.1016/j.mce.2009.02.027
  12. Celec P, Ostatnikova D, Caganova M, et al (2005). Endocrine and cognitive effects of short-time soybean consumption in women. Gynecol Obstet Invest, 59, 62-6. https://doi.org/10.1159/000081895
  13. Dillingham BL, McVeigh BL, Lampe JW, et al (2007). Soy protein isolates of varied isoflavone content do not influence serum thyroid hormones in healthy young men. Thyroid, 17, 131-7. https://doi.org/10.1089/thy.2006.0206
  14. Doerge DR, Chang HC (2002). Inactivation of thyroid peroxidase by soy isoflavones, in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci, 777, 269-79. https://doi.org/10.1016/S1570-0232(02)00214-3
  15. Dong JY, Qin LQ (2011). Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat, 125, 315-23. https://doi.org/10.1007/s10549-010-1270-8
  16. Duncan AM, Phipps WR, Kurzer MS (2003). Phyto-oestrogens. Best Pract Res Clin Endocrinol Metab, 17, 253-71. https://doi.org/10.1016/S1521-690X(02)00103-3
  17. Esaki H, Kawakishi S, Morimitsu Y, et al (1999). New potent antioxidative o-dihydroxyisoflavones in fermented Japanese soybean products. Biosci Biotechnol Biochem, 63, 1637-9. https://doi.org/10.1271/bbb.63.1637
  18. Franke AA, Custer LJ (1994). High-performance liquid chromatographic assay of isoflavonoids and coumestrol from human urine. J Chromatogr B Biomed Appl, 662, 47-60. https://doi.org/10.1016/0378-4347(94)00390-4
  19. Furspan PB, Freedman RR (1998). Effect of modulators of protein tyrosine kinase activity on gender-related differences in vascular reactivity at reduced temperature. J Cardiovasc Pharmacol, 32, 728-35. https://doi.org/10.1097/00005344-199811000-00008
  20. Hooper L, Ryder JJ, Kurzer MS, et al (2009). Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis. Hum Reprod Update, 15, 423-40. https://doi.org/10.1093/humupd/dmp010
  21. Horn-Ross PL, Barnes S, Lee M, et al (2000). Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control, 11, 289-98. https://doi.org/10.1023/A:1008995606699
  22. Jones DJ, Lim CK, Ferry DR, et al (1998). Determination of quercetin in human plasma by HPLC with spectrophotometric or electrochemical detection. Biomed Chromatogr, 12, 232-5. https://doi.org/10.1002/(SICI)1099-0801(199807/08)12:4<232::AID-BMC740>3.0.CO;2-1
  23. Kang HB, Zhang YF, Yang JD, et al (2012). Study on soy isoflavone consumption and risk of breast cancer and survival. Asian Pac J Cancer Prev, 13, 995-8. https://doi.org/10.7314/APJCP.2012.13.3.995
  24. Kim J (2008). Protective effects of Asian dietary items on cancers - soy and ginseng. Asian Pac J Cancer Prev, 9, 543-8.
  25. Kim J, Kang M, Lee JS, et al (2011). Fermented and nonfermented soy food consumption and gastric cancer in Japanese and Korean populations: a meta-analysis of observational studies. Cancer Sci, 102, 231-44. https://doi.org/10.1111/j.1349-7006.2010.01770.x
  26. King RA, Broadbent JL, Head RJ (1996). Absorption and excretion of the soy isoflavone genistein in rats. J Nutr, 126, 176-82.
  27. Klejdus B, Mikelova R, Petrlova J, et al (2005). Evaluation of isoflavone aglycon and glycoside distribution in soy plants and soybeans by fast column high-performance liquid chromatography coupled with a diode-array detector. J Agric Food Chem, 53, 5848-52. https://doi.org/10.1021/jf0502754
  28. Ko KP, Park SK, Park B, et al (2010). Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort. Cancer Epidemiol Biomarkers Prev, 19, 1292-300. https://doi.org/10.1158/1055-9965.EPI-09-1004
  29. Kuiper GG, Carlsson B, Grandien K, et al (1997). Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology, 138, 863-70.
  30. Kuiper GG, Enmark E, Pelto-Huikko M, et al (1996). Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA, 93, 5925-30. https://doi.org/10.1073/pnas.93.12.5925
  31. Kuiper GG, Lemmen JG, Carlsson B, et al (1998). Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139, 4252-63.
  32. Kulling SE, Honig DM, Metzler M (2001). Oxidative metabolism of the soy isoflavones daidzein and genistein in humans in vitro and in vivo. J Agric Food Chem, 49, 3024-33. https://doi.org/10.1021/jf0012695
  33. Kulling SE, Honig DM, Simat TJ, et al (2000). Oxidative in vitro metabolism of the soy phytoestrogens daidzein and genistein. J Agric Food Chem, 48, 4963-72. https://doi.org/10.1021/jf000524i
  34. Kulling SE, Lehmann L, Metzler M (2002). Oxidative metabolism and genotoxic potential of major isoflavone phytoestrogens. J Chromatogr B Analyt Technol Biomed Life Sci, 777, 211-8. https://doi.org/10.1016/S1570-0232(02)00215-5
  35. Kurzer MS, Xu X (1997). Dietary phytoestrogens. Annu Rev Nutr, 17, 353-81. https://doi.org/10.1146/annurev.nutr.17.1.353
  36. Kwon DY, Daily JW 3rd, Kim HJ, et al (2010). Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutr Res, 30, 1-13. https://doi.org/10.1016/j.nutres.2009.11.004
  37. Lampe JW, Karr SC, Hutchins AM, et al (1998). Urinary equol excretion with a soy challenge: influence of habitual diet. Proc Soc Exp Biol Med, 217, 335-9. https://doi.org/10.3181/00379727-217-44241
  38. Li SH, Liu XX, Bai YY, et al (2010). Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am J Clin Nutr, 91, 480-6. https://doi.org/10.3945/ajcn.2009.28203
  39. Liggins J, Bluck LJ, Runswick S, et al (2000). Daidzein and genistein contents of vegetables. Br J Nutr, 84, 717-25.
  40. Mathias K, Ismail B, Corvalan CM, et al (2006). Heat and pH effects on the conjugated forms of genistin and daidzin isoflavones. J Agric Food Chem, 54, 7495-502. https://doi.org/10.1021/jf061322a
  41. Minatoya M, Kutomi G, Asakura S, et al (2013). Equol, adiponectin, insulin levels and risk of breast cancer. Asian Pac J Cancer Prev, 14, 2191-9. https://doi.org/10.7314/APJCP.2013.14.4.2191
  42. Mortensen A, Kulling SE, Schwartz H, et al (2009). Analytical and compositional aspects of isoflavones in food and their biological effects. Mol Nutr Food Res, 53, 266-309. https://doi.org/10.1002/mnfr.200800134
  43. Morton MS, Arisaka O, Miyake N, et al (2002). Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr, 132, 3168-71.
  44. Nakajima N, Nozaki N, Ishihara K, et al (2005). Analysis of isoflavone content in tempeh, a fermented soybean, and preparation of a new isoflavone-enriched tempeh. J Biosci Bioeng, 100, 685-7. https://doi.org/10.1263/jbb.100.685
  45. Pase MP, Grima NA, Sarris J (2011). The effects of dietary and nutrient interventions on arterial stiffness: a systematic review. Am J Clin Nutr, 93, 446-54. https://doi.org/10.3945/ajcn.110.002725
  46. Patisaul HB, Jefferson W (2010). The pros and cons of phytoestrogens. Front Neuroendocrinol, 31, 400-19. https://doi.org/10.1016/j.yfrne.2010.03.003
  47. Pillow PC, Duphorne CM, Chang S, et al (1999). Development of a database for assessing dietary phytoestrogen intake. Nutr Cancer, 33, 3-19. https://doi.org/10.1080/01635589909514742
  48. Pilsakova L, Riecansky I, Jagla F (2010). The physiological actions of isoflavone phytoestrogens. Physiol Res, 59, 651-64.
  49. Piontek M, Hengels KJ, Porschen R, et al (1993). Antiproliferative effect of tyrosine kinase inhibitors in epidermal growth factor-stimulated growth of human gastric cancer cells. Anticancer Res, 13, 2119-23.
  50. Prasad S, Phromnoi K, Yadav VR, et al (2010). Targeting inflammatory pathways by flavonoids for prevention and treatment of cancer. Planta Med, 76, 1044-63. https://doi.org/10.1055/s-0030-1250111
  51. Qin LQ, Xu JY, Wang PY, et al (2006). Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol (Tokyo), 52, 428-36. https://doi.org/10.3177/jnsv.52.428
  52. Rakosky J (1975). Soy protein in foods: their use and regulations in the U.S. J Am Oil Chem Soc, 52, 272-4. https://doi.org/10.1007/BF02637724
  53. Ricci E, Cipriani S, Chiaffarino F, et al (2010). Effects of soy isoflavones and genistein on glucose metabolism in perimenopausal and postmenopausal non-Asian women: a meta-analysis of randomized controlled trials. Menopause, 17, 1080-6. https://doi.org/10.1097/gme.0b013e3181dd05a9
  54. Sakai T, Kogiso M (2008). Soy isoflavones and immunity. J Med Invest, 55, 167-73. https://doi.org/10.2152/jmi.55.167
  55. Setchell KD (1998). Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr, 68, 1333-46.
  56. Setchell KD, Cassidy A (1999). Dietary isoflavones: biological effects and relevance to human health. J Nutr, 129, 758-67.
  57. Sfakianos J, Coward L, Kirk M, et al (1997). Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J Nutr, 127, 1260-8.
  58. Shimazu T, Inoue M, Sasazuki S, et al (2011). Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev, 20, 419-27. https://doi.org/10.1158/1055-9965.EPI-10-1025
  59. Shor D, Sathyapalan T, Atkin SL, et al (2012). Does equol production determine soy endocrine effects? Eur J Nutr, 51, 389-98. https://doi.org/10.1007/s00394-012-0331-7
  60. Sugiyama Y, Masumori N, Fukuta F, et al (2013). Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev, 14, 1-4. https://doi.org/10.7314/APJCP.2013.14.1.1
  61. Taku K, Melby MK, Takebayashi J, et al (2010). Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr, 19, 33-42.
  62. Thomas JM, Lutz SF (2001). Soy protein lowers fat and saturated fat in school lunch beef and pork entrees. J Am Diet Assoc, 101, 461-3. https://doi.org/10.1016/S0002-8223(01)00118-3
  63. Tikkanen MJ, Wahala K, Ojala S, et al (1998). Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proc Natl Acad Sci USA, 95, 3106-10. https://doi.org/10.1073/pnas.95.6.3106
  64. van Pelt AM, de Rooij DG, van der Burg B, et al (1999). Ontogeny of estrogen receptor-beta expression in rat testis. Endocrinology, 140, 478-83.
  65. Verkasalo PK, Appleby PN, Allen NE, et al (2001). Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition). Br J Nutr, 86, 415-21. https://doi.org/10.1079/BJN2001424
  66. Wahala K, Rasku S, Parikka K (2002). Deuterated phytoestrogen flavonoids and isoflavonoids for quantitation. J Chromatogr B Analyt Technol Biomed Life Sci, 777, 111-22. https://doi.org/10.1016/S1570-0232(02)00096-X
  67. Wang CC, Prasain JK, Barnes S (2002). Review of the methods used in the determination of phytoestrogens. J Chromatogr B Analyt Technol Biomed Life Sci, 777, 3-28. https://doi.org/10.1016/S1570-0232(02)00341-0
  68. Wang GJ, Lapcik O, Hampl R, et al (2000). Time-resolved fluoroimmunoassay of plasma daidzein and genistein. Steroids, 65, 339-48. https://doi.org/10.1016/S0039-128X(00)00089-1
  69. Wilkinson AP, Wahala K, Williamson G (2002). Identification and quantification of polyphenol phytoestrogens in foods and human biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci, 777, 93-109. https://doi.org/10.1016/S1570-0232(02)00095-8
  70. Wiseman H, Casey K, Clarke DB, et al (2002). Isoflavone aglycon and glucoconjugate content of high- and low-soy U.K. foods used in nutritional studies. J Agric Food Chem, 50, 1404-10. https://doi.org/10.1021/jf011243t
  71. Wu Q, Wang M, Simon JE (2004). Analytical methods to determine phytoestrogenic compounds. J Chromatogr B Analyt Technol Biomed Life Sci, 812, 325-55. https://doi.org/10.1016/j.jchromb.2004.08.008
  72. Xu X, Harris KS, Wang HJ, et al (1995). Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr, 125, 2307-15.
  73. Yakimchuk K, Jondal M, Okret S (2013). Estrogen receptor alpha and beta in the normal immune system and in lymphoid malignancies. Mol Cell Endocrinol, 375, 121-9. https://doi.org/10.1016/j.mce.2013.05.016
  74. Yan L, Spitznagel EL (2009). Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr, 89, 1155-63. https://doi.org/10.3945/ajcn.2008.27029
  75. Yu O, Jung W, Shi J, et al (2000). Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues. Plant Physiol, 124, 781-94. https://doi.org/10.1104/pp.124.2.781
  76. Yu X, Zhu J, Mi M, et al (2012). Anti-angiogenic genistein inhibits VEGF-induced endothelial cell activation by decreasing PTK activity and MAPK activation. Med Oncol, 29, 349-57. https://doi.org/10.1007/s12032-010-9770-2
  77. Zhang YF, Kang HB, Li BL, et al (2012). Positive effects of soy isoflavone food on survival of breast cancer patients in China. Asian Pac J Cancer Prev, 13, 479-82. https://doi.org/10.7314/APJCP.2012.13.2.479
  78. Zhu YY, Zhou L, Jiao SC, et al (2011). Relationship between soy food intake and breast cancer in China. Asian Pac J Cancer Prev, 12, 2837-40.

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