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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Effects of Isolated Isoflavones Intake on Health

Author(s): Antonella Smeriglio*, Antonella Calderaro, Marcella Denaro, Giuseppina Laganà and Ersilia Bellocco

Volume 26 , Issue 27 , 2019

Page: [5094 - 5107] Pages: 14

DOI: 10.2174/0929867324666171006143047

Price: $65


Background: Isoflavones are naturally occurring flavonoids, commonly found in the food consumed for centuries in the East-Asian population, characterized by a structure able to exert nonsteroidal estrogen-like activity on human cells. They have attracted researcher interest all around the word, following the results obtained in epidemiological and clinical studies. The involvement of isoflavones and their metabolites in various biological processes suggests that they can influence several metabolic pathways and can influence the gene expression at epigenetic level, involving effects that probably are due to early life exposure. They show positive health effects on several diseases, especially in the prevention of coronary heart and neurological diseases, hormone-related cancers, osteoporosis, and postmenopausal symptoms.

Methods: We have performed a critical evaluation of available literature trough a structured search of bibliographic databases about isoflavones health promoting properties, risk assessment and mechanisms of action. In addition, we supplied useful information on their biochemical properties, sources and bioavailability.

Results: Although these molecules have been the subjects of numerous researches, their role for the wellness of the human organism remains controversial. Moreover, there are substantial inconsistencies between the results obtained by epidemiologic studies conducted on Eastern population, which found high health promoting properties, and Western clinical trials, which found much less positive effects.

Conclusion: Further epidemiologic studies and well-designed prospective human studies are to determine the beneficial effects of isoflavones exposure, as well as establishing its safe therapeutic.

Keywords: Isoflavones, health promotion properties, risk-assessment, daidzein, genistein, glycitein.

Sanadgol, N.; Zahedani, S.S.; Sharifzadeh, M.; Khalseh, R.; Barbari, G.R.; Abdollahi, M. Recent updates in imperative natural compounds for healthy brain and nerve function: A systematic review of implications for multiple sclerosis. Curr. Drug Targets, 2016, 18(13), 1499-1517.
[] [PMID: 27829351]
Bulgakov, V.P.; Vereshchagina, Y.V.; Veremeichik, G.N. Anticancer polyphenols from cultured plant cells: production and new bioengineering strategies. Curr. Med. Chem., 2017, 25(36), 4671-4692.
[] [PMID: 28595545]
Ahmed, T.; Javed, S.; Tariq, A.; Budzyńska, B.; D’Onofrio, G.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Daidzein and its effects on brain. Curr. Med. Chem., 2017, 24(4), 365-375.
[] [PMID: 27804870]
Smeriglio, A.; Denaro, M.; Trombetta, D. Dietary Phytochemicals and Endrocrine-related Activities: an update. Mini Rev. Med. Chem., 2017, 18(16), 1382-1397.
[] [PMID: 28699495]
Scheiber, M.D.; Liu, J.H.; Subbiah, M.T.; Rebar, R.W.; Setchell, K.D. Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause, 2001, 8(5), 384-392.
[] [PMID: 11528367]
Chiechi, L.M.; Secreto, G.; Vimercati, A.; Greco, P.; Venturelli, E.; Pansini, F.; Fanelli, M.; Loizzi, P.; Selvaggi, L. The effects of a soy rich diet on serum lipids: the Menfis randomized trial. Maturitas, 2002, 41(2), 97-104.
[] [PMID: 11836040]
Sarkar, F.H.; Li, Y. Soy isoflavones and cancer prevention. Cancer Invest., 2003, 21(5), 744-757.
[] [PMID: 14628433]
Moriguchi, E.H.; Moriguchi, Y.; Yamori, Y. Impact of diet on the cardiovascular risk profile of Japanese immigrants living in Brazil: contributions of World Health Organization CARDIAC and MONALISA studies. Clin. Exp. Pharmacol. Physiol., 2004, 31(Suppl. 2), S5-S7.
[] [PMID: 18254187]
Ikeda, Y.; Iki, M.; Morita, A.; Kajita, E.; Kagamimori, S.; Kagawa, Y.; Yoneshima, H. Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J. Nutr., 2006, 136(5), 1323-1328.
[] [PMID: 16614424]
Wu, A.H.; Yu, M.C.; Tseng, C.C.; Pike, M.C. Epidemiology of soy exposures and breast cancer risk. Br. J. Cancer, 2008, 98(1), 9-14.
[] [PMID: 18182974]
Al-Dosary, D.I.; Alhomida, A.S.; Ola, M.S. Protective effects of dietary flavonoids in diabetic induced retinal neurodegeneration. Curr. Drug Targets, 2016, 18(13), 1468-1476.
[] [PMID: 27697035]
Wang, B.F.; Wang, J.S.; Lu, J.F.; Kao, T.H.; Chen, B.H. Antiproliferation effect and mechanism of prostate cancer cell lines as affected by isoflavones from soybean cake. J. Agric. Food Chem., 2009, 57(6), 2221-2232.
[] [PMID: 19292464]
Barnes, S. The biochemistry, chemistry and physiology of the isoflavones in soybeans and their food products. Lymphat. Res. Biol., 2010, 8(1), 89-98.
[] [PMID: 20235891]
Kao, T.H.; Chen, B.H. Functional components in soybean cake and their effects on antioxidant activity. J. Agric. Food Chem., 2006, 54(20), 7544-7555.
[] [PMID: 17002420]
Pan, M.H.; Lai, C.S.; Ho, C.T. Anti-inflammatory activity of natural dietary flavonoids. Food Funct., 2010, 1(1), 15-31.
[] [PMID: 21776454]
Kao, T.H.; Wu, W.M.; Hung, C.F.; Wu, W.B.; Chen, B.H. Anti-inflammatory effects of isoflavone powder produced from soybean cake. J. Agric. Food Chem., 2007, 55(26), 11068-11079.
[] [PMID: 18052238]
Korde, L.A.; Wu, A.H.; Fears, T.; Nomura, A.M.; West, D.W.; Kolonel, L.N.; Pike, M.C.; Hoover, R.N.; Ziegler, R.G. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol. Biomarkers Prev., 2009, 18(4), 1050-1059.
[] [PMID: 19318430]
Leclercq, G.; Jacquot, Y. Interactions of isoflavones and other plant derived estrogens with estrogen receptors for prevention and treatment of breast cancer-considerations concerning related efficacy and safety. J. Steroid Biochem. Mol. Biol., 2014, 139, 237-244.
[] [PMID: 23274118]
Zhao, L.; Brinton, R.D. Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. J. Med. Chem., 2005, 48(10), 3463-3466.
[] [PMID: 15887952]
Wang, X. Structure, mechanism and engineering of plant natural product glycosyltransferases. FEBS Lett., 2009, 583(20), 3303-3309.
[] [PMID: 19796637]
Wang, X. Structure, function, and engineering of enzymes in isoflavonoid biosynthesis. Funct. Integr. Genomics, 2011, 11(1), 13-22.
[] [PMID: 21052759]
Klejdus, B.; Mikelová, R.; Petrlová, J.; Potesil, D.; Adam, V.; Stiborová, M.; Hodek, P.; Vacek, J.; Kizek, R.; Kubán, V. 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., 2005, 53(15), 5848-5852.
[] [PMID: 16028964]
Romani, A.; Vignolini, P.; Galardi, C.; Aroldi, C.; Vazzana, C.; Heimler, D. Polyphenolic content in different plant parts of soy cultivars grown under natural conditions. J. Agric. Food Chem., 2003, 51(18), 5301-5306.
[] [PMID: 12926874]
Veitch, N.C. Isoflavonoids of the leguminosae. Nat. Prod. Rep., 2007, 24(2), 417-464.
[] [PMID: 17390003]
Veitch, N.C. Isoflavonoids of the leguminosae. Nat. Prod. Rep., 2009, 26(6), 776-802.
[] [PMID: 19471685]
Mazur, W. Phytoestrogen content in foods. Baillieres Clin. Endocrinol. Metab., 1998, 12(4), 729-742.
[] [PMID: 10384822]
Esaki, H.; Kawakishi, S.; Morimitsu, Y.; Osawa, T. New potent antioxidative o-dihydroxyisoflavones in fermented Japanese soybean products. Biosci. Biotechnol. Biochem., 1999, 63(9), 1637-1639.
[] [PMID: 10540753]
Dixon, R.A. Phytoestrogens. Annu. Rev. Plant Biol., 2004, 55, 225-261.
[] [PMID: 15377220]
Bhagwat, S.; Haytowitz, D.B.; Holden, J.M. USDA database for the isoflavone content of selected foods, release 2.0. U.S. department of agriculture, agri-cultural research service, nutrient data laboratory. Available at: (Accessed on Feburary 24, 2017 ).
Andersen, O.M.; Markham, K.R. Flavonoids. Chemistry, biochemistry and applications, 2006. (ed.). Taylor & Francis, Boca Raton, FL, USA
Lee, J.; Renita, M.; Fioritto, R.J.; St Martin, S.K.; Schwartz, S.J.; Vodovotz, Y. Isoflavone characterization and antioxidant activity of ohio soybeans. J. Agric. Food Chem., 2004, 52(9), 2647-2651.
[] [PMID: 15113172]
Day, A.J.; DuPont, M.S.; Ridley, S.; Rhodes, M.; Rhodes, M.J.; Morgan, M.R.; Williamson, G. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett., 1998, 436(1), 71-75.
[] [PMID: 9771896]
Sfakianos, J.; Coward, L.; Kirk, M.; Barnes, S. Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J. Nutr., 1997, 127(7), 1260-1268.
[] [PMID: 9202077]
King, R.A.; Broadbent, J.L.; Head, R.J. Absorption and excretion of the soy isoflavone genistein in rats. J. Nutr., 1996, 126(1), 176-182.
[] [PMID: 8558299]
Ronis, M.J.; Little, J.M.; Barone, G.W.; Chen, G.; Radominska-Pandya, A.; Badger, T.M. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. J. Med. Food, 2006, 9(3), 348-355.
[] [PMID: 17004897]
Setchell, K.D.; Clerici, C. Equol: history, chemistry, and formation. J. Nutr., 2010, 140(7), 1355S-1362S.
[] [PMID: 20519412]
Ko, K.P. Isoflavones: chemistry, analysis, functions and effects on health and cancer. Asian Pac. J. Cancer Prev., 2014, 15(17), 7001-7010.
[] [PMID: 25227781]
Pilšáková, L.; Riečanský, I.; Jagla, F. The physiological actions of isoflavone phytoestrogens. Physiol. Res., 2010, 59(5), 651-664.
[PMID: 20406033]
Sunita, P.; Pattanayak, S.P. Phytoestrogens in postmenopausal indications: A theoretical perspective. Pharmacogn. Rev., 2011, 5(9), 41-47.
[] [PMID: 22096317]
Shanle, E.K.; Xu, W. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem. Res. Toxicol., 2011, 24(1), 6-19.
[] [PMID: 21053929]
Rahman, H.P.; Hofland, J.; Foster, P.A. In touch with your feminine side: how oestrogen metabolism impacts prostate cancer. Endocr. Relat. Cancer., 2016.pii: ERC-16-0118.
Smeriglio, A.; Trombetta, D.; Marcoccia, D.; Narciso, L.; Mantovani, A.; Lorenzetti, S. Intracellular distribution and biological effects of phytochemicals in a sex steroid- sensitive model of human prostate adenocarcinoma. Anticancer. Agents Med. Chem., 2014, 14(10), 1386-1396.
[] [PMID: 24962071]
Mahmoud, A.M.; Yang, W.; Bosland, M.C. Soy isoflavones and prostate cancer: a review of molecular mechanisms. J. Steroid Biochem. Mol. Biol., 2014, 140, 116-132.
[] [PMID: 24373791]
Mahmoud, A.M.; Al-Alem, U.; Ali, M.M.; Bosland, M.C. Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation. J. Steroid Biochem. Mol. Biol., 2015, 152, 62-75.
[] [PMID: 25931004]
Maggiolini, M.; Vivacqua, A.; Carpino, A.; Bonofiglio, D.; Fasanella, G.; Salerno, M.; Picard, D.; Andó, S. The mutant androgen receptor T877A mediates the proliferative but not the cytotoxic dose-dependent effects of genistein and quercetin on human LNCaP prostate cancer cells. Mol. Pharmacol., 2002, 62(5), 1027-1035.
[] [PMID: 12391264]
Rosenberg Zand, R.S.; Jenkins, D.J.; Diamandis, E.P. Flavonoids and steroid hormone-dependent cancers. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2002, 777(1-2), 219-232.
[] [PMID: 12270215]
Marino, M.; Pellegrini, M.; La Rosa, P.; Acconcia, F. Susceptibility of estrogen receptor rapid responses to xenoestrogens: Physiological outcomes. Steroids, 2012, 77(10), 910-917.
[] [PMID: 22410438]
Choi, S.Y.; Ha, T.Y.; Ahn, J.Y.; Kim, S.R.; Kang, K.S.; Hwang, I.K.; Kim, S. Estrogenic activities of isoflavones and flavones and their structure-activity relationships. Planta Med., 2008, 74(1), 25-32.
[] [PMID: 18095219]
Lephart, E.D. Modulation of aromatase by phytoestrogens. Enzyme Res., 2015, 2015594656
[] [PMID: 26798508]
Hwang, K.A.; Choi, K.C. Anticarcinogenic effects of dietary phytoestrogens and their chemopreventive mechanisms. Nutr. Cancer, 2015, 67(5), 796-803.
[] [PMID: 25996655]
Adjakly, M.; Ngollo, M.; Dagdemir, A.; Judes, G.; Pajon, A.; Karsli-Ceppioglu, S.; Penault-Llorca, F.; Boiteux, J.P.; Bignon, Y.J.; Guy, L.; Bernard-Gallon, D. Prostate cancer: The main risk and protective factors-Epigenetic modifications. Ann. Endocrinol. (Paris), 2015, 76(1), 25-41.
[] [PMID: 25592466]
Williamson, G.; Manach, C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am. J. Clin. Nutr., 2005, 81(1)(Suppl.), 243S-255S.
[] [PMID: 15640487]
Marín, L.; Miguélez, E.M.; Villar, C.J.; Lombó, F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. BioMed Res. Int., 2015.2015905215
[] [PMID: 25802870]
de Azevedo, W.F. Opinion paper: targeting multiple Cyclin-Dependent Kinases (CDKs): a new strategy for molecular docking studies. Curr. Drug Targets, 2016, 17(1), 2.
[] [PMID: 26687602]
Levin, N.M.B.; Pintro, V.O.; de Avila, M.B.; de Mattos, B.B.; De Azevedo, W.F., Jr Understanding the structural basis for inhibition of cyclin-dependent kinases. New pieces in the molecular puzzle. Curr. Drug Targets, 2017, 18(9), 1104-1111.
[] [PMID: 27848884]
Krystof, V.; Uldrijan, S. Cyclin-dependent kinase inhibitors as anticancer drugs. Curr. Drug Targets, 2010, 11(3), 291-302.
[] [PMID: 20210754]
Blagden, S.; de Bono, J. Drugging cell cycle kinases in cancer therapy. Curr. Drug Targets, 2005, 6(3), 325-335.
[] [PMID: 15857291]
Coracini, J.D.; de Azevedo, W.F., Jr Shikimate kinase, a protein target for drug design. Curr. Med. Chem., 2014, 21(5), 592-604.
[] [PMID: 24164195]
Varinska, L.; Gal, P.; Mojzisova, G.; Mirossay, L.; Mojzis, J. Soy and breast cancer: focus on angiogenesis. Int. J. Mol. Sci., 2015, 16(5), 11728-11749.
[] [PMID: 26006245]
Chen, F.P.; Chien, M.H. Phytoestrogens induce apoptosis through a mitochondria/caspase pathway in human breast cancer cells. Climacteric, 2014, 17(4), 385-392.
[] [PMID: 24299158]
Spagnuolo, C.; Russo, G.L.; Orhan, I.E.; Habtemariam, S.; Daglia, M.; Sureda, A.; Nabavi, S.F.; Devi, K.P.; Loizzo, M.R.; Tundis, R.; Nabavi, S.M. Genistein and cancer: current status, challenges, and future directions. Adv. Nutr., 2015, 6(4), 408-419.
[] [PMID: 26178025]
Han, R.M.; Tian, Y.X.; Liu, Y.; Chen, C.H.; Ai, X.C.; Zhang, J.P.; Skibsted, L.H. Comparison of flavonoids and isoflavonoids as antioxidants. J. Agric. Food Chem., 2009, 57(9), 3780-3785.
[] [PMID: 19296660]
Cemeli, E.; Baumgartner, A.; Anderson, D. Antioxidants and the comet assay. Mutat. Res., 2009, 681(1), 51-67.
[] [PMID: 18602333]
Sueishi, Y.; Hori, M.; Ishikawa, M.; Matsu-Ura, K.; Kamogawa, E.; Honda, Y.; Kita, M.; Ohara, K. Scavenging rate constants of hydrophilic antioxidants against multiple reactive oxygen species. J. Clin. Biochem. Nutr., 2014, 54(2), 67-74.
[] [PMID: 24688213]
Zhang, Y.; Li, Q.; Zhou, D.; Chen, H. Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/β-catenin signalling and reduces colon pre-neoplasia in rats. Br. J. Nutr., 2013, 109(1), 33-42.
[] [PMID: 22716201]
Takashima, M.; Nara, K.; Niki, E.; Yoshida, Y.; Hagihara, Y.; Stowe, M.; Horie, M. Evaluation of biological activities of a groundnut (Apios americana Medik) extract containing a novel isoflavone. Food Chem., 2013, 138(1), 298-305.
[] [PMID: 23265491]
Foti, P.; Erba, D.; Riso, P.; Spadafranca, A.; Criscuoli, F.; Testolin, G. Comparison between daidzein and genistein antioxidant activity in primary and cancer lymphocytes. Arch. Biochem. Biophys., 2005, 433(2), 421-427.
[] [PMID: 15581598]
Sierens, J.; Hartley, J.A.; Campbell, M.J.; Leathem, A.J.; Woodside, J.V. In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog. Carcinog. Mutagen., 2002, 22(3), 227-234.
[] [PMID: 11948633]
Mezei, O.; Banz, W.J.; Steger, R.W.; Peluso, M.R.; Winters, T.A.; Shay, N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J. Nutr., 2003, 133(5), 1238-1243.
[] [PMID: 12730403]
Molla, M.D.; Hidalgo-Mora, J.J.; Soteras, M.G. Phytotherapy as alternative to hormone replacement therapy., 2011.
Cano, A.; García-Pérez, M.A.; Tarín, J.J. Isoflavones and cardiovascular disease. Maturitas, 2010, 67(3), 219-226.
[] [PMID: 20728290]
Ma, D.F.; Qin, L.Q.; Wang, P.Y.; Katoh, R. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. Eur. J. Clin. Nutr., 2008, 62(2), 155-161.
[] [PMID: 17392695]
Ming, L.G.; Chen, K.M.; Xian, C.J. Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. J. Cell. Physiol., 2013, 228(3), 513-521.
[] [PMID: 22777826]
Li, B.; Yu, S. Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation. Biol. Pharm. Bull., 2003, 26(6), 780-786.
[] [PMID: 12808286]
Yu, Z.; Li, W.; Zhang, L. [Effects of genistein on cell proliferation and differentiation in human osteoblast] Wei Sheng Yan Jiu , 2004, 33(5), 569-571.
[PMID: 15612482]
Suh, K.S.; Koh, G.; Park, C.Y.; Woo, J.T.; Kim, S.W.; Kim, J.W.; Park, I.K.; Kim, Y.S. Soybean isoflavones inhibit tumor necrosis factor-alpha-induced apoptosis and the production of interleukin-6 and prostaglandin E2 in osteoblastic cells. Phytochemistry, 2003, 63(2), 209-215.
[] [PMID: 12711143]
Sliwiński, L.; Folwarczna, J.; Janiec, W.; Grynkiewicz, G.; Kuzyk, K. Differential effects of genistein, estradiol and raloxifene on rat osteoclasts in vitro. Pharmacol. Rep., 2005, 57(3), 352-359.
[PMID: 15985718]
Zheng, X.; Lee, S.K.; Chun, O.K. Soy isoflavones and osteoporotic bone loss: a review with an emphasis on modulation of bone remodeling. J. Med. Food, 2016, 19(1), 1-14.
[] [PMID: 26670451]
Messina, M. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients, 2016, 8(12)E754
[] [PMID: 27886135]
Ae Park, S.; Choi, M.S.; Cho, S.Y.; Seo, J.S.; Jung, U.J.; Kim, M.J.; Sung, M.K.; Park, Y.B.; Lee, M.K. Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci., 2006, 79(12), 1207-1213.
[] [PMID: 16647724]
Talaei, M.; Pan, A. Role of phytoestrogens in prevention and management of type 2 diabetes. World J. Diabetes, 2015, 6(2), 271-283.
[] [PMID: 25789108]
Lee, J.S. Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sci., 2006, 79(16), 1578-1584.
[] [PMID: 16831449]
Fu, Z.; Gilbert, E.R.; Pfeiffer, L.; Zhang, Y.; Fu, Y.; Liu, D. Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes. Appl. Physiol. Nutr. Metab., 2012, 37(3), 480-488.
[] [PMID: 22509809]
Fu, Z.; Zhang, W.; Zhen, W.; Lum, H.; Nadler, J.; Bassaganya-Riera, J.; Jia, Z.; Wang, Y.; Misra, H.; Liu, D. Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice. Endocrinology, 2010, 151(7), 3026-3037.
[] [PMID: 20484465]
Babu, P.V.; Liu, D.; Gilbert, E.R. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J. Nutr. Biochem., 2013, 24(11), 1777-1789.
[] [PMID: 24029069]
Liu, D.; Zhen, W.; Yang, Z.; Carter, J.D.; Si, H.; Reynolds, K.A. Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes, 2006, 55(4), 1043-1050.
[] [PMID: 16567527]
Yang, H.; Li, F.; Xiong, X.; Kong, X.; Zhang, B.; Yuan, X.; Fan, J.; Duan, Y.; Geng, M.; Li, L.; Yin, Y. Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs. Mol. Cell. Endocrinol., 2013, 365(1), 44-51.
[] [PMID: 22986217]
Li, F.N.; Li, L.L.; Yang, H.S.; Yuan, X.X.; Zhang, B.; Geng, M.M.; Xiao, C.W.; Yin, Y.L. Regulation of soy isoflavones on weight gain and fat percentage: evaluation in a Chinese Guangxi minipig model. Animal, 2011, 5(12), 1903-1908.
[] [PMID: 22440466]
Jiang, G.; Li, L.; Fan, J.; Zhang, B.; Oso, A.O.; Xiao, C.; Yin, Y. Dietary soy isoflavones differentially regulate expression of the lipid-metabolic genes in different white adipose tissues of the female Bama mini-pigs. Biochem. Biophys. Res. Commun., 2015, 461(1), 159-164.
[] [PMID: 25866186]
Gilbert, E.R.; Liu, D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct., 2013, 4(2), 200-212.
[] [PMID: 23160185]
Blum, S.C.; Heaton, S.N.; Bowman, B.M.; Hegsted, M.; Miller, S.C. Dietary soy protein maintains some indices of bone mineral density and bone formation in aged ovariectomized rats. J. Nutr., 2003, 133(5), 1244-1249.
[] [PMID: 12730404]
Mihalache, G.; Mihalache, G.D.; Indrei, L.L.; Indrei, A.; Hegsted, M. [Phytoestrogens role in bone functional structure protection in the ovariectomized rat] Rev. Med. Chir. Soc. Med. Nat. Ias, 2002, 106(1), 89-92.
[PMID: 12635367]
Pie, J.E.; Park, J.H.; Park, Y.H.; Ryu, Y.M.; Kim, K.N.; Suh, S.W.; Becker, K.G.; Cho-Chung, Y.S.; Kim, M.K. Effect of genistein on the expression of bone metabolism genes in ovariectomized mice using a cDNA microarray. J. Nutr. Biochem., 2006, 17(3), 157-164.
[] [PMID: 16169203]
Sakai, T.; Kogiso, M. Soy isoflavones and immunity. J. Med. Invest., 2008, 55(3-4), 167-173.
[] [PMID: 18797128]
Gu, Y.; Zhu, C.F.; Iwamoto, H.; Chen, J.S. Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis. World J. Gastroenterol., 2005, 11(41), 6512-6517.
[] [PMID: 16425425]
Chodon, D.; Banu, S.M.; Padmavathi, R.; Sakthisekaran, D. Inhibition of cell proliferation and induction of apoptosis by genistein in experimental hepatocellular carcinoma. Mol. Cell. Biochem., 2007, 297(1-2), 73-80.
[] [PMID: 17006617]
Yanagihara, K.; Takigahira, M.; Mihara, K.; Kubo, T.; Morimoto, C.; Morita, Y.; Terawaki, K.; Uezono, Y.; Seyama, T. Inhibitory effects of isoflavones on tumor growth and cachexia in newly established cachectic mouse models carrying human stomach cancers. Nutr. Cancer, 2013, 65(4), 578-589.
[] [PMID: 23659450]
Peng, B.; Cao, J.; Yi, S.; Wang, C.; Zheng, G.; He, Z. Inhibition of proliferation and induction of G1-phase cell-cycle arrest by dFMGEN, a novel genistein derivative, in lung carcinoma A549 cells. Drug Chem. Toxicol., 2013, 36(2), 196-204.
[] [PMID: 22931124]
Zhang, T.; Wang, F.; Xu, H.X.; Yi, L.; Qin, Y.; Chang, H.; Mi, M.T.; Zhang, Q.Y. Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury. Br. J. Nutr., 2013, 109(2), 223-235.
[] [PMID: 22716961]
Ju, Y.H.; Allred, K.F.; Allred, C.D.; Helferich, W.G. Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations. Carcinogenesis, 2006, 27(6), 1292-1299.
[] [PMID: 16537557]
Michikawa, T.; Inoue, M.; Sawada, N.; Tanaka, Y.; Yamaji, T.; Iwasaki, M.; Shimazu, T.; Sasazuki, S.; Mizokami, M.; Tsugane, S. Plasma isoflavones and risk of primary liver cancer in Japanese women and men with hepatitis virus infection: a nested case-control study. Cancer Epidemiol. Biomarkers Prev., 2015, 24(3), 532-537.
[] [PMID: 25542831]
Ko, K.P.; Park, S.K.; Park, B.; Yang, J.J.; Cho, L.Y.; Kang, C.; Kim, C.S.; Gwack, J.; Shin, A.; Kim, Y.; Kim, J.; Yang, H.K.; Kang, D.; Chang, S.H.; Shin, H.R.; Yoo, K.Y. Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean Multicenter Cancer Cohort. Cancer Epidemiol. Biomarkers Prev., 2010, 19(5), 1292-1300.
[] [PMID: 20447921]
Hara, A.; Sasazuki, S.; Inoue, M.; Miura, T.; Iwasaki, M.; Sawada, N.; Shimazu, T.; Yamaji, T.; Tsugane, S. Plasma isoflavone concentrations are not associated with gastric cancer risk among Japanese men and women. J. Nutr., 2013, 143(8), 1293-1298.
[] [PMID: 23761654]
Shimazu, T.; Inoue, M.; Sasazuki, S.; Iwasaki, M.; Sawada, N.; Yamaji, T.; Tsugane, S. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am. J. Clin. Nutr., 2010, 91(3), 722-728.
[] [PMID: 20071645]
Shimazu, T.; Inoue, M.; Sasazuki, S.; Iwasaki, M.; Sawada, N.; Yamaji, T.; Tsugane, S. Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol. Biomarkers Prev., 2011, 20(3), 419-427.
[] [PMID: 21239686]
Jiang, R.; Botma, A.; Rudolph, A.; Hüsing, A.; Chang-Claude, J. Phyto-oestrogens and colorectal cancer risk: a systematic review and dose-response meta-analysis of observational studies. Br. J. Nutr., 2016, 116(12), 2115-2128.
[] [PMID: 28091359]
Kucuk, O. Soy foods, isoflavones, and breast cancer. Cancer, 2017, 123(11), 1901-1903.
[] [PMID: 28263364]
U.S. National Library of Medicine Database of privately and publicly funded clinical studies conducted around the world., (Accessed March 01, 2017).
Panel on food additives and nutrient sources added to food scientific opinion on the risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones. EFSA J., 2015, 13, 4246.
Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause, 2015, 22(11), 1155-1172.
[] [PMID: 26382310]
Patel, S.; Zhou, C.; Rattan, S.; Flaws, J.A. Effects of endocrine-disrupting chemicals on the ovary. Biol. Reprod., 2015, 93(1), 20.
[] [PMID: 26063868]
Leclercq, G.; de Cremoux, P.; This, P.; Jacquot, Y. Lack of sufficient information on the specificity and selectivity of commercial phytoestrogens preparations for therapeutic purposes. Maturitas, 2011, 68(1), 56-64.
[] [PMID: 21074339]
Ye, H.; Ng, H.W.; Sakkiah, S.; Ge, W.; Perkins, R.; Tong, W.; Hong, H. Pathway analysis revealed potential diverse health impacts of flavonoids that bind estrogen receptors. Int. J. Environ. Res. Public Health, 2016, 13(4), 373.
[] [PMID: 27023590]
Qiu, L.X.; Chen, T. Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease. World J. Gastroenterol., 2015, 21(4), 1099-1107.
[] [PMID: 25632182]
Penza, M.; Montani, C.; Romani, A.; Vignolini, P.; Pampaloni, B.; Tanini, A.; Brandi, M.L.; Alonso-Magdalena, P.; Nadal, A.; Ottobrini, L.; Parolini, O.; Bignotti, E.; Calza, S.; Maggi, A.; Grigolato, P.G.; Di Lorenzo, D. Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. Endocrinology, 2006, 147(12), 5740-5751.
[] [PMID: 16959845]
Strakovsky, R.S.; Lezmi, S.; Flaws, J.A.; Schantz, S.L.; Pan, Y.X.; Helferich, W.G. Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats. Toxicol. Sci., 2014, 138(1), 161-174.
[] [PMID: 24361872]
Cederroth, C.R.; Zimmermann, C.; Nef, S. Soy, phytoestrogens and their impact on reproductive health. Mol. Cell. Endocrinol., 2012, 355(2), 192-200.
[] [PMID: 22210487]
Eustache, F.; Mondon, F.; Canivenc-Lavier, M.C.; Lesaffre, C.; Fulla, Y.; Berges, R.; Cravedi, J.P.; Vaiman, D.; Auger, J. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility. Environ. Health Perspect., 2009, 117(8), 1272-1279.
[] [PMID: 19672408]
Jefferson, W.N.; Patisaul, H.B.; Williams, C.J. Reproductive consequences of developmental phytoestrogen exposure. Reproduction, 2012, 143(3), 247-260.
[] [PMID: 22223686]

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