Isoflavonoids — an overview of their biological activities and potential health benefits

Open access

Isoflavonoids — an overview of their biological activities and potential health benefits

There are many biological activities attributed to isoflavonoids. The majority of them could be beneficial and some of them may be detrimental, depending on specific circumstances. Isoflavonoids play an important role in human nutrition as health promoting natural chemicals. They belong to plant secondary metabolites that mediate diverse biological functions through numerous pathways. They are structurally similar to estrogens, exerting both estrogenic and antiestrogenic properties in various tissues. The results of epidemiologic studies exploring the role of isoflavonoids in human health have been inconclusive. Some studies support the notion of a protective effect of their consumption in immunomodulation, cognition, risk reduction of certain cancers, cardiovascular and skin diseases, osteoporosis and obesity, as well as relief of menopausal symptoms. Other studies failed to demonstrate any effects.

Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S. (2008). Dietary soy isoflavone intake and risk of colorectal cancer in the Japan Public Health Cancer-based prospective study. Epidem Biomark Prev 17 (8): 2128-2135.

Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SA. (2004). Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial. Breast Can Res 6 (3): 170-179.

Barnes S. (2004). Soy isoflavones - phytoestrogens and what else? J Nut 134: 1225S-1228S.

Bezek S, Ujhazy E, Mach M, Navarova J, Dubovicky M. (2008). Developmental origin of chronic diseases: toxicological implication. Interdisc Toxicol 1 (1): 29-31.

Birt DF, Hendrich S, Wang W. (2001). Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 90 (2-3): 157-177.

Boccia S, La Torre G, Gianfagna F, Mannocci A, Ricciardi G. (2005). N-Acetyltransferase 2 status and gastric cancer risk: a preliminary meta-analysis. Ital J Pub Health 2: 53-57.

Cesarone MR, Grossi MG, Di Renzo, A, Errich S, Schönlau F, Wilmer JL, Lange M, Blimenfeld J. (2009). Accelerated antioxidant bioavailability of OPC-3® bioflavonoids administered as isotonic solution. Phytother Res 23 (6): 775-777.

Chen Y, Gammon MD, Teitelbaum SL, Britton JA, Terry MB, Shantakumar S, Eng SM, Wang Q, Gurvich I, Neugut AI, Santella RM, Ahsan H. (2008). Estrogen-biosynthesis gene CYP17 and its interactions with reproductive hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project. Carcinogen 29 (4): 766-771.

Cherdshewasart W, Sutjit W. (2008). Correlation of antioxidant activity and major isoflavonoid contents of the phytoestrogen-rich Pueraria mirifica and Pueraria libata tubers. Phytomed 15 (1-2): 38-43.

Chodon D, Ramamurty N, Sakthisekan D. (2007). Inhibition of cell proliferation and induction of apoptosis by genistein in hepatocellular carcinoma. Tox in Vitro 20 (5): 887-891.

Chrzan BG, Bradford PG. (2007). Phytoestrogens activate estrogen receptor β1 and estrogenic responses in human breast and bone cancer cell lines. Mol Nutr Food Res 51: 171-177.

Dixon RA, Summer LW. (2003.) Legume natural products: Understanding and manipulating complex pathways for human and animal health. Plant Physiol 131: 878-885.

Duffy C, Perez K, Partridge A. (2007). Implications of phytoestrogen intake for breast cancer. CA Can J Clin 57: 260-277.

Eliassen AH, Missmer SA, Tworoger SS, Hankinson SE. (2008). Circulating 2-hydroxy and 16a-hydroxy estrone levels and risk of breast cancer among post-menopausal women. Can Epidem Biomark Prev 17 (8): 2029-2035.

Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Gaudet MM, Abrahamson PE, Bell P, Schroeder JC, Teiltelbaum SL, Neugut AI, Gammon MD. (2007). Dietary flavonoid intake and breast cancer survival among women on Long Island. Can Epidem Biomark Prev 16: (11): 2285-2292.

Goodman MT, Shvetsov YB, Wilkens LR, Franke AA, Marchand LL, Kazaku KK, Nomura AMY, Henderson BE, Kolonel LN. (2009). Urinary phytoestrogen excretion and postmenopausal breast cancer risk: the multiethnic cohort study. Can Prev Res 2: 887.

Hirschberg AL, Edlund M, Svane G, Azavedo E, Skoog L, von Schoultz B. (2007). An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women. Menopause 14 (1): 89-96.

Hedlund TE, van Bokhaven A, Johannes WU, Nordeen SK, Ogden LG. (2005) Prostatic fluid concentrations of isoflavonoids in soy consumers are sufficient to inhibit growth of benign and malignant epithelial cells in vitro.The Prost 66 (5): 557-566.

Ito C, Murata T, Itoigawa M, Nakao K, Kumagai M, Kaneda N, Furukawa H. (2006). Induction of apoptosis by isoflavonoids from leaves of Milletia taiwaniana in human leukemia HL-60 cells. Planta Med 72 (5): 424-429.

Iwasaki M, Inoue M, Otani T, Sasazuki S, Kurashi N, Miura T, Yamoto S, Tsugane S. (2008). Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from Japan Public Health Center-base prospective study group. J Clin Oncol 26 (10): 1677-1683.

Ju IH, Allred KF, Allred CD, Helferich WG. (2006). Genistein stimulates growth of human breast cancer cells in a novel postmenopausal animal model, with low plasma estradiol concentrations. Carcinogen 27: 1292-1299.

Kousidou OC, Tzanakakis GN, Karamanos NK. (2006). Effects of natural isoflavonoid genistein on growth, signaling pathway and gene expression of matrix macromolecules by breast cancer cells. Mini Rev Med Chem 6 (3): 331-337.

Kralova J, Pekarova M, Drabikova K, Jancinova V, Nosal R, Ciz M, Lojek A. (2008). The effects of dithiaden on nitric oxide production by RAW 264.7 cells. Interdisc Toxicol 1 (3-4): 214-217.

Lampe JW. (2009). Is equol the key to the efficacy of soy foods? Am J Clin Nutr 89: 1664S-1667S.

Lockwood B. (2008). The beneficial effects of soy isoflavones in osteoporosis of the elderly. Elderly Nutr AgroFood Ind Hi-tech 19 (5):38-41.

Liu B, Edgerton S, Yang X. (2005). Low-dose dietary phytoestrogen abrogates tamoxifen-associated mammary tumor prevention. Can Res 65: 879-886.

Maskarinec G, Williams AE, Carlin L. (2003). Mammographic densities in a oneyear isoflavone intervention. Eur J Can Prev 12 (2):165-169.

Maskarinec G, Hebshi S, Custer L, Franke AA. (2008a). The relation of soy intake and isoflavone levels in nipple aspirate fluid. Eu J Can Prev 17(1): 67-70.

Maskarinec G, Watts K, Kagihara J, Hebshi SM, Franke AA. (2008b) Urinary isoflavonoid is similar after consuming soya milk and miso soup in Japanese-American women. Brit J Nutr 100: 424-429.

Maskarinec G, Verheus M, Steinberg FM, Amato P, Cramer M, Lewis RD, Murray MJ, Yong RL, Wong WW. (2009). Various doses of isoflavones do not modify mammographic density in postmenopausal women. J Nutr 139 (5): 981-986.

Messina M, Wood CE. (2008). Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J 7(1): 17-28.

Messina M, McCaskill-Stevens W, Lampe JW. (2006). Addressing the soy and breast cancer relatioship: review, commentary, and workshop proceedings. J Natl Can Inst 98 (18): 1275-1284.

Miadokova E, Masterova I, Vlckova V, Duhova V, Toth J. (2002). Antimutagenic potential of homoisoflavonoids from Muscari racemosum.J Ethnopharmacol 18: 381-386.

Murata IC, Itoigawa M, Nakao K, Kumagai M, Kaneda N, Furukawa H. (2006). Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells. Planta Med 72 (5): 424-429.

Myasoedova VA, Sobenin IA. (2008). Background, rationale and design of clinical study of the effect of isoflavonoid-rich botanicals on natural history of atherosclerosis in women. Atheroscler Suppl. 9 (1): 171.

Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Oba S, Shimizu H. (2008). Soy isoflavone intake is not associated with the development od cedar pollinosis in adults. J Nutr 138: 1372-1376

Ørgaard A, Jensen L. (2008). The effects of soy isoflavones on obesity Exp Biol Med 233: 1066-1080.

Perry DL, Spedick JM, McCoy TP, Adams MR, Franke AA, Cline JM. (2007). Dietary soy protein containing isoflavonoids does not adversely affect the reproductive tract of male cynomolgus macaques (Macaca fascicularis).J Nutr 137: 1390-1394.

Piller R, Chang-Claude J, Linseisen J. (2006). Plasma enterolactone and genistein and the risk of premenopausal breast cancer. Eu J Can Prev 15 (3): 225-232.

Raju J, Bielecki A, Caldwell D, Lok E, Taylor M, Kapal K, Curran I, Cooke GM, Bird RP, Mehta R. (2009). Soy isoflavones modulate azoxymethane-induced rat colon carcinogenesis exposed pre- and postnatally and inhibit growth of DLD-1 human colon adenocarcinoma cells increasing the expression of estrogen receptor beta. Nutr 139 (3): 474-4781.

Ralston L, Subramanian S, Matsuto M, Yu O. (2005). Partial reconstruction of flavoid and soflavoid biosynthesis in yeast using soybean Type I and Type II chalcone isomerases. Plant Physiol 137 (4): 1375-1388.

Reiter RJ, Paredes SD, Kormaz A, Jou M-J, Tan D-X. (2008). Melatonin combats molecular terrorism at the mitochondrial level Interdisc Toxicol 1 (2): 137-149.

Rice S, Mason HD, Whitehead SA. (2006). Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells. J Ster Biochem Mol Biol 101 (4-5): 216-225.

Ryan-Borchers TA, Park JS, Chew BP, McGuire MK, Fournier LR, Beerman KA. (2006). Soy isoflavones modulate immune function in healthy postmenopausal women. Am J Clin Nutr 83: 118-1125.

Sabudak T, Guler N. (2009). Trifolium L.- A review on its phytochemical and pharmacological profile. Phytother Res 23: 439-446.

Shen P, Liu MH, Ng TY, Chan YH, Long EL. (2006) Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARalpha, PPAR gamma, and adipocyte differentiation in vitro J Nutr 136: 899-905.

Scarpato R, Paganucci L, Bertoli A, Fiore L, Pistelli L, Federico G. (2008). Licoflavone C attenuates the genotoxicity of cancer drugs in human peripheral lymphocytes. Phytother Res 22 (12): 1650-1654.

Shen P, Liu MH, Ng TY, Chan YH, Yong EL. (2006). Differential effects of isoflavones, from Astragalus membranaceus and Puerarua thomsonii, on the activation of PPARalpha, PPAR gamma, and adipocyte differentiation in vitro.J Nutr 136: 899-905.

Stienstra R, Duval C, Ller M, Kersten S. (2007). PPARs, obesity, and inflammation. PPAR Res. 2007: 95974.

Su Y, Simmen RCM. (2009). Soy isoflavone genistein upregulates epithelian adhesion molecule E-cadherin expression and β-catenin signaling in mammary epithelial cells. Carcinogen 30 (2): 331-339.

Talbott KE, Gammon MD, Kibriva MG, Chen Y, Teilbaum SL, Long CM, Gurvich I, Santella RM, Ahsan H. (2008). A Cyp 19 (aromatase) polymorphism is associated with increased premenopausal breast cancer risk. Breast Can Res Treat 111 (3): 481-487.

Tamini RM, Hankinson SE, Coldiz GA, Byrne C. (2005). Endogenous sex hormone levels and mammographic density among postmenopausal women. Can Epidem Biomark Prev 14: 2641-2647.

Thorp AA, Howe PR, Mori TA, Coates AM, Buckley JD, Hodgson J, Mansour J, Meyer BJ. (2008.) Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am J Clin Nutr 88 (2): 298-304.

Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE, van der Schouw YT. (2008). Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Can Epidem Biomark Prev 17 (10): 2632-2638.

Wang Y, Gho WM, Chan FL, Chen S, Leung LK. (2008). The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Brit J Nutr 99: 303-310.

Wood CE, Appt S, Clarkson TB, Franke AA, Lees C, Doerge DR, Cline JM. (2006). Effects of high-dose soy isoflavones and equol on reproductive tissues in female cynomolgus monkeys. Biol Rep 75 (3): 477-486.

Wood CE, Register TC, Cline JM. (2007). Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal female monkeys. Carcinogen 28 (4): 801-808.

Widyarini S, Domanski D, Painter N, Reeve VE. (2006). Estrogen receptor signaling protects against immune suppression by UV radiation exposure. Proc Nat Acad Sci 103 (34): 12837-12842.

Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

Journal Information


CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671

Cited By

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 405 345 34
PDF Downloads 131 115 19