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Applied Microbiology and Biotechnology

, Volume 97, Issue 4, pp 1489–1500 | Cite as

Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health

  • Shen-Shih Chiang
  • Tzu-Ming PanEmail author
Mini-Review

Abstract

Phytoestrogens are a class of bioactive compounds derived from plants and exert various estrogenic and antiestrogenic effects. Estrogen deficiency osteoporosis has become a serious problem in elderly women. The use of ovariectomized (OVX) rat or mice models to simulate the postmenopausal condition is well established. This review aimed to clarify the sources, biochemistry, absorption, metabolism, and mode of action of phytoestrogens on bone health in intervention studies. In vitro, phytoestrogens promote protein synthesis, osteoprotegerin/receptor activation of nuclear factor-kappa B ligand ratio, and mineralization by osteoblast-like cells (MC3T3-E1). In the OVX murine model, administration of phytoestrogens can inhibit differentiation and activation of osteoclasts, expression of tartrate-resistant acid phosphatase, and secretion of pyridinoline compound. Phytoestrogens also enhance bone formation and increase bone mineral density and levels of alkaline phosphatase, osteocalcin, osteopontin, and α1(I) collagen. Results of mechanistic studies have indicated that phytoestrogens suppress the rate of bone resorption and enhance the rate of bone formation.

Keywords

Phytoestrogens Postmenopausal Ovariectomized model Antiosteoporosis 

References

  1. Alcantara EH, Shin MY, Sohn HY, Park YM, Kim T, Lim JH, Jeong HJ, Kwon ST, Kwun IS (2011) Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells. J Nutr Biochem 22:1055–1063CrossRefGoogle Scholar
  2. Allred CD, Twaddle NC, Allred KF, Goeppinger TS, Churchwell MI, Ju YH, Helferich WG, Doerge DR (2005) Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized BALB/c mice. J Agric Food Chem 53:8542–8550CrossRefGoogle Scholar
  3. Andlauer W, Kolb J, Fürst P (2000a) Absorption and metabolism of genistin in the isolated rat small intestine. FEBS Lett 475:127–130CrossRefGoogle Scholar
  4. Andlauer W, Kolb J, Stehle P, Fürst P (2000b) Absorption and metabolism of genistein in isolated rat small intestine. J Nutr 130:843–846Google Scholar
  5. Bhathena SJ, Velasquez MT (2002) Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr 76:1191–1201Google Scholar
  6. Bouxsein ML, Myers KS, Shultz KL, Donahue LR, Rosen CJ, Beamer WG (2005) Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Miner Res 20:1058–1092CrossRefGoogle Scholar
  7. Branca F (2003) Dietary phyto-oestrogens and bone health. Proc Nutr Soc 62:877–887CrossRefGoogle Scholar
  8. Cano A, Dapía S, Noguera I, Pineda B, Hermenegildo C, del Val R, Caeiro JR, García-Pérez MA (2008) Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice. Osteoporos Int 19:793–800CrossRefGoogle Scholar
  9. Carmichael SL, Gonzalez-Feliciano AG, Ma C, Shaw GM, Cogswell ME (2011) Estimated dietary phytoestrogen intake and major food sources among women during the year before pregnancy. Nutr J 10:105–114CrossRefGoogle Scholar
  10. Chen X, Garner SC, Quarles LD, Anderson JJ (2003) Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation. J Nutr Biochem 14:342–349CrossRefGoogle Scholar
  11. Chen J, Lin H, Hu M (2005) Absorption and metabolism of genistein and its five isoflavone analogs in human intestinal Caco-2 model. Cancer Chemother Pharmacol 55:159–169CrossRefGoogle Scholar
  12. Chen H, Zhou X, Emura S, Shoumura S (2009) Site-specific bone loss in senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis. Exp Gerontol 44:792–798CrossRefGoogle Scholar
  13. Chiang SS, Pan TM (2011) Antiosteoporotic effects of Lactobacillus-fermented soy skim milk on bone mineral density and the microstructure of femoral bone in ovariectomized mice. J Agric Food Chem 59:7734–7742CrossRefGoogle Scholar
  14. Chiang SS, Chang SP, Pan TM (2011) Osteoprotective effect of Monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis. J Agric Food Chem 59:9150–9157CrossRefGoogle Scholar
  15. Chiang SS, Liao JW, Pan TM (2012) Effect of bioactive compounds in lactobacilli-fermented soy skim milk on femoral bone microstructure of aging mice. J Sci Food Agric 92:328–335CrossRefGoogle Scholar
  16. de Kleijn MJ, van der Schouw YT, Wilson PW, Adlercreutz H, Mazur W, Grobbee DE, Jacques PF (2001) Intake of dietary phytoestrogens is low in post-menopausal women in the United States: the Framingham study. J Nutrition 131:1826–1832Google Scholar
  17. Delmas PD (2002) Treatment of postmenopausal osteoporosis. Lancet 359:2018–2026CrossRefGoogle Scholar
  18. Draper CR, Edel MJ, Dick IM, Randall AG, Martin GB, Prince RL (1997) Phytoestrogens reduce bone loss and bone resorption in oophorectomized rats. J Nutr 127:1795–1799Google Scholar
  19. Duncan AM, Phipps WR, Kurzer MS (2003) Phyto-oestrogens. Best Pract Res Clin Endocrinol Metab 17:253–271CrossRefGoogle Scholar
  20. Egermann M, Goldhahn J, Schneider E (2005) Animal models for fracture treatment in osteoporosis. Osteoporos Int 16:S129–S138CrossRefGoogle Scholar
  21. Emmanuel S, Amalraj T, Ignacimuthu S (2001) Hepatoprotective effect of coumestans isolated from the leaves of Wedelia calendulacea Less. in paracetamol induced liver damage. Indian J Exp Biol 39:1305–1307Google Scholar
  22. Filipović B, Sosić-Jurjević B, Ajdzanović V, Brkić D, Manojlović-Stojanoski M, Milosević V, Sekulić M (2010) Daidzein administration positively affects thyroid C cells and bone structure in orchidectomized middle-aged rats. Osteoporos Int 21:1609–1616CrossRefGoogle Scholar
  23. Fonseca D, Ward WE (2004) Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice. Bone 35:489–497CrossRefGoogle Scholar
  24. Fujioka M, Uehara M, Wu J, Adlercreutz H, Suzuki K, Kanazawa K, Takeda K, Yamada K, Ishimi Y (2004) Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice. J Nutr 134:2623–2637Google Scholar
  25. Fujioka M, Sudo Y, Okumura M, Wu J, Uehara M, Takeda K, Hosokawa Y, Yamada K, Ikegami S, Ishimi Y (2007) Differential effects of isoflavones on bone formation in growing male and female mice. Metabolism 56:1142–1148CrossRefGoogle Scholar
  26. Garrett IR, Mundy GR (2002) The role of statins as potential targets for bone formation. Arthritis Res 4:237–240CrossRefGoogle Scholar
  27. Gennari C (1999) Calcitonin, bone-active isoflavones and vitamin D metabolites. Osteoporos Int 9:S81–S90CrossRefGoogle Scholar
  28. Gong G, Qin Y, Huang W (2011) Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo. Phytomedicine 18:456–463CrossRefGoogle Scholar
  29. Hartholt KA, Oudshoorn C, Zielinski SM, Burgers PT, Panneman MJ, van Beeck EF, Patka P, van der Cammen TJ (2011) The epidemic of hip fractures: are we on the right track? PLoS One 6:e22227CrossRefGoogle Scholar
  30. Hertrampf T, Schleipen B, Offermanns C, Velders M, Laudenbach U, Diel P (2009) Comparison of the bone protective effects of an isoflavone-rich diet with dietary and subcutaneous administrations of genistein in ovariectomized rats. Toxicol Lett 184:198–203CrossRefGoogle Scholar
  31. Horiuchi N, Maeda T (2006) Statins and bone metabolism. Oral Dis 15:85–101CrossRefGoogle Scholar
  32. Hsu KH, Chang CC, Tsai HD, Tsai FJ, Hsieh YY (2008) Effects of yam and diosgenin on calpain systems in skeletal muscle of ovariectomized rats. Taiwan J Obstet Gynecol 47:180–186CrossRefGoogle Scholar
  33. Huang CH, Liu DZ, Jan TR (2010) Diosgenin, a plant-derived sapogenin, enhances regulatory T-cell immunity in the intestine of mice with food allergy. J Nat Prod 73:1033–1037CrossRefGoogle Scholar
  34. Ishimi Y (2009) Soybean isoflavones in bone health. Forum Nutr Basel Karger 61:104–116CrossRefGoogle Scholar
  35. Ishimi Y (2010) Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice. J Nutr 140:1373S–1376SCrossRefGoogle Scholar
  36. Ishimi Y, Arai N, Wang X, Wu J, Umegaki K, Miyaura C, Takeda A, Ikegami S (2000) Difference in effective dosage of genistein on bone and uterus in ovariectomized mice. Biochem Biophys Res Commun 274:697–701CrossRefGoogle Scholar
  37. Iwaniec UT, Yuan D, Power RA, Wronski TJ (2006) Strain-dependent variations in the response of cancellous bone to ovariectomy in mice. J Bone Miner Res 21:1068–1074CrossRefGoogle Scholar
  38. Johnell O (1997) The socioeconomic burden of fractures: today and in the 21st century. Am J Med 103:20S–26SCrossRefGoogle Scholar
  39. Kanno S, Hirano S, Kayama F (2004) Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells. Toxicology 196:137–145CrossRefGoogle Scholar
  40. Kärkkäinen M, Tuppurainen M, Salovaara K, Sandini L, Rikkonen T, Sirola J, Honkanen R, Jurvelin J, Alhava E, Kröger H (2010) Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65–71 years: a 3-year randomized population-based trial (OSTPRE-FPS). Osteoporos Int 21:2047–2055CrossRefGoogle Scholar
  41. Keen R (2007) Osteoporosis: strategies for prevention and management. Best Pract Res Clin Rheumatol 21:109–122CrossRefGoogle Scholar
  42. Kim KW, Suh SJ, Lee TK, Ha KT, Kim JK, Kim KH, Kim DI, Jeon JH, Moon TC, Kim CH (2008) Effect of safflower seeds supplementation on stimulation of the proliferation, differentiation and mineralization of osteoblastic MC3T3-E1 cells. J Ethnopharmacol 115:42–49CrossRefGoogle Scholar
  43. Kim DW, Yoo KY, Lee YB, Lee KH, Sohn HS, Lee SJ, Cho KH, Shin YK, Hwang IK, Won MH, Kim DW (2009) Soy isoflavones mitigate long-term femoral and lumbar vertebral bone loss in middle-aged ovariectomized mice. J Med Food 12:536–541CrossRefGoogle Scholar
  44. Kim TH, Jung JW, Ha BG, Hong JM, Park EK, Kim HJ, Kim SY (2011) The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss. J Nutr Biochem 22:8–15CrossRefGoogle Scholar
  45. Kimira Y, Tajima K, Ohta A, Ishimi Y, Katsumata S, Suzuki K, Adlercreutz H, Uehara M (2012) Synergistic effect of isoflavone glycosides and fructooligosaccharides on postgastrectomy osteopenia in rats. J Clin Biochem Nutr 51:156–160CrossRefGoogle Scholar
  46. Klinck J, Boyd SK (2008) The magnitude and rate of bone loss in ovariectomized mice differs among inbred strains as determined by longitudinal in vivo micro-computed tomography. Cif Tissue Int 83:70–79CrossRefGoogle Scholar
  47. Kröger H, Kärkkäinen M, Honkanen R (2010) Calcium and vitamin D in promotion of postmenopausal bone health. Womens Health (Lond Engl) 6:773–776CrossRefGoogle Scholar
  48. Lagari VS, Levis S (2010) Phytoestrogens and bone health. Curr Opin Endocrinol Diabetes Obes 17:546–553CrossRefGoogle Scholar
  49. Lee KH, Choi EM (2005) Biochanin A stimulates osteoblastic differentiation and inhibits hydrogen peroxide-induced production of inflammatory mediators in MC3T3-E1 cells. Biol Pharm Bull 28:1948–1953CrossRefGoogle Scholar
  50. Legette LL, Martin BR, Shahnazari M, Lee WH, Helferich WG, Qian J, Waters DJ, Arabshahi A, Barnes S, Welch J, Bostwick DG, Weaver CM (2009) Supplemental dietary racemic equol has modest benefits to bone but has mild uterotropic activity in ovariectomized rats. J Nutr 139:1908–1913CrossRefGoogle Scholar
  51. Li CY, Schaffler MB, Wolde-Semait HT, Hernandez CJ, Jepsen KJ (2005) Genetic background influences cortical bone response to ovariectomy. J Bone Miner Res 20:2150–2158CrossRefGoogle Scholar
  52. Liu Y, Hu M (2002) Absorption and metabolism of flavonoids in the Caco-2 cell culture model and a perfused rat intestinal model. Drug Metab Dispos 30:370–377CrossRefGoogle Scholar
  53. Mathey J, Puel C, Kati-Coulibaly S, Bennetau-Pelissero C, Davicco MJ, Lebecque P, Horcajada MN, Coxam V (2004) Fructooligosaccharides maximize bone-sparing effects of soy isoflavone-enriched diet in the ovariectomized rat. Calcif Tissue Int 75:169–179CrossRefGoogle Scholar
  54. Mathey J, Mardon J, Fokialakis N, Puel C, Kati-Coulibaly S, Mitakou S, Bennetau-Pelissero C, Lamothe V, Davicco MJ, Lebecque P, Horcajada MN, Coxam V (2007) Modulation of soy isoflavones bioavailability and subsequent effects on bone health in ovariectomized rats: the case for equol. Osteoporos Int 18:671–679CrossRefGoogle Scholar
  55. Messina MJ (1999) Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 70:439S–450SGoogle Scholar
  56. Michihara S, Tanaka T, Uzawa Y, Moriyama T, Kawamura Y (2012) Puerarin exerted anti-osteoporotic action independent of estrogen receptor-mediated pathway. J Nutr Sci Vitaminol 58:202–209CrossRefGoogle Scholar
  57. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G (1999) Stimulation of bone formation in vitro and in rodents by statins. Science 286:1946–1949CrossRefGoogle Scholar
  58. Office of the Surgeon General (US) (2004) Bone health and osteoporosis: a report of the surgeon general. Office of the Surgeon General (US), Rockville, MD, pp 1–404Google Scholar
  59. Ohtomo T, Uehara M, Peñalvo JL, Adlercreutz H, Katsumata S, Suzuki K, Takeda K, Masuyama R, Ishimi Y (2008) Comparative activities of daidzein metabolites, equol and O-desmethylangolensin, on bone mineral density and lipid metabolism in ovariectomized mice and in osteoclast cell cultures. Eur J Nutr 47:273–279CrossRefGoogle Scholar
  60. Ono Y, Fukaya Y, Imai S, Yamakuni T (2008) Beneficial effects of Ajuga decumbens on osteoporosis and arthritis. Biol Pharm Bull 31:1199–1204CrossRefGoogle Scholar
  61. Peacock M (1998) Effects of calcium and vitamin D insufficiency on the skeleton. Osteoporos Int 8:S45–S51CrossRefGoogle Scholar
  62. Pogoda P, Priemel M, Schilling AF, Gebauer M, Catalá-Lehnen P, Barvencik F, Beil FT, Münch C, Rupprecht M, Müldner C, Rueger JM, Schinke T, Amling M (2005) Mouse models in skeletal physiology and osteoporosis: experiences and data on 14839 cases from the Hamburg Mouse Archives. J BoneMiner Metab 23:97–102CrossRefGoogle Scholar
  63. Rachoń D, Seidlová-Wuttke D, Vortherms T, Wuttke W (2007) Effects of dietary equol administration on ovariectomy induced bone loss in Sprague–Dawley rats. Maturitas 58:308–315CrossRefGoogle Scholar
  64. Ren P, Ji H, Shao Q, Chen X, Han J, Sun Y (2007) Protective effects of sodium daidzein sulfonate on trabecular bone in ovariectomized rats. Pharmacology 79:129–136CrossRefGoogle Scholar
  65. Riggs BL, Khosla S, Melton LJ (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773CrossRefGoogle Scholar
  66. Setchell KD, Cassidy A (1999) Dietary isoflavones: biological effects and relevance to human health. J Nutr 129:758S–767SGoogle Scholar
  67. Simons R, Gruppen H, Bovee TF, Verbruggen MA, Vincken JP (2012) Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs). Food Funct 3:810–827CrossRefGoogle Scholar
  68. Sliwiński L, Folwarczna J, Nowińska B, Cegieła U, Pytlik M, Kaczmarczyk-Sedlak I, Trzeciak H, Trzeciak HI (2009) A comparative study of the effects of genistein, estradiol and raloxifene on the murine skeletal system. Acta Biochim Pol 56:261–270Google Scholar
  69. Son IS, Kim JH, Sohn HY, Son KH, Kim JS, Kwon CS (2007) Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats. Biosci Biotechnol Biochem 71:3063–3071CrossRefGoogle Scholar
  70. Sugimoto E, Yamaguchi M (2000) Stimulatory effect of daidzein in osteoblastic MC3T3-E1 cells. Biochem Pharmacol 59:471–475CrossRefGoogle Scholar
  71. Suh KS, Koh G, Park CY, Woo JT, Kim SW, Kim JW, Park IK, Kim YS (2003) Soybean isoflavones inhibit tumor necrosis factor-alpha-induced apoptosis and the production of interleukin-6 and prostaglandin E2 in osteoblastic cells. Phytochemistry 63:209–215CrossRefGoogle Scholar
  72. Suh KS, Choi EM, Kwon M, Chon S, Oh S, Woo JT, Kim SW, Kim JW, Kim YS (2009) Kaempferol attenuates 2-deoxy-d-ribose-induced oxidative cell damage in MC3T3-E1 osteoblastic cells. Biol Pharm Bull 32:746–749CrossRefGoogle Scholar
  73. Taguchi H, Chen H, Yano R, Shoumura S (2006) Comparative effects of milk and soymilk on bone loss in adult ovariectomized osteoporosis rat. Okajimas Folia Anat Jpn 83:53–59CrossRefGoogle Scholar
  74. Thompson LU, Robb P, Serraino M, Cheung F (1991) Mammalian lignan production from various foods. Nutr Cancer 16:43–52CrossRefGoogle Scholar
  75. Thompson LU, Rickard SE, Cheung F, Kenaschuk EO, Obermeyer WR (1997) Variability in anticancer lignan levels in flaxseed. Nutr Cancer 27:26–30CrossRefGoogle Scholar
  76. Thompson LU, Boucher BA, Liu Z, Cotterchio M, Kreiger N (2006) Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutr Cancer 54:184–201CrossRefGoogle Scholar
  77. Tousen Y, Abe F, Ishida T, Uehara M, Ishimi Y (2011) Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein. Metabolism 60:1425–1432CrossRefGoogle Scholar
  78. Tsuji M, Yamamoto H, Sato T, Mizuha Y, Kawai Y, Taketani Y, Kato S, Terao J, Inakuma T, Takeda E (2009) Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice. J Bone Miner Metab 27:673–681CrossRefGoogle Scholar
  79. Turner RT (1999) Mice, estrogen and postmenopausal osteoporosis. J Bone Miner Res 14:187–191CrossRefGoogle Scholar
  80. Uchiyama S, Yamaguchi M (2007) Genistein and zinc synergistically enhance gene expression and mineralization in osteoblastic MC3T3-E1 cells. Int J Mol Med 19:213–220Google Scholar
  81. Uchiyama S, Yamaguchi M (2008) Anabolic effect of beta-cryptoxanthin in osteoblastic MC3T3-E1 cells is enhanced with 17beta-estradiol, genistein, or zinc sulfate in vitro: the unique effect with zinc on Runx2 and alpha1(I) collagen mRNA expressions. Mol Cell Biochem 307:209–219CrossRefGoogle Scholar
  82. Usui T (2006) Pharmaceutical prospects of phytoestrogens. Endocr J 53:7–20CrossRefGoogle Scholar
  83. Wang HJ, Murphy PA (1994) Isoflavone content in commercial soybean foods. J Agric Food Chem 42:1666–1673CrossRefGoogle Scholar
  84. Wang SF, Jiang Q, Ye YH, Li Y, Tan RX (2005) Genistein derivatives as selective estrogen receptor modulators: sonochemical synthesis and in vivo anti-osteoporotic action. Bioorg Med Chem 13:4880–4890CrossRefGoogle Scholar
  85. Wang ZL, Sun JY, Wang DN, Xie YH, Wang SW, Zhao WM (2006) Pharmacological studies of the large-scaled purified genistein from Huaijiao (Sophora japonica-Leguminosae) on anti-osteoporosis. Phytomedicine 13:718–723CrossRefGoogle Scholar
  86. Wang J, Shang F, Jiang R, Liu L, Wang S, Hou J, Huan M, Mei Q (2007a) Nitric oxide-donating genistein prodrug: design, synthesis, and bioactivity on MC3T3-E1 cells. J Pharmacol Sci 104:82–89CrossRefGoogle Scholar
  87. Wang JW, Xu SW, Yang DS, Lv RK (2007b) Locally applied simvastatin promotes fracture healing in ovariectomized rat. Osteoporos Int 18:1641–1650CrossRefGoogle Scholar
  88. Wang J, Shang F, Mei Q, Wang J, Zhang R, Wang S (2008) NO-donating genistein prodrug alleviates bone loss in ovariectomised rats. Swiss Med Wkly 138:602–607Google Scholar
  89. Ward WE, Kim S, Chan D, Fonseca D (2005) Serum equol, bone mineral density and biomechanical bone strength differ among four mouse strains. J Nutr Biochem 16:743–749CrossRefGoogle Scholar
  90. Wronski TJ, Dann LM, Scott KS, Cintrón M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366CrossRefGoogle Scholar
  91. Wu J, Wang XX, Takasaki M, Ohta A, Higuchi M, Ishimi Y (2001) Cooperative effects of exercise training and genistein administration on bone mass in ovariectomized mice. J Bone Miner Res 16:1829–1836CrossRefGoogle Scholar
  92. Wu J, Wang X, Chiba H, Higuchi M, Nakatani T, Ezaki O, Cui H, Yamada K, Ishimi Y (2004) Combined intervention of soy isoflavone and moderate exercise prevents body fat elevation and bone loss in ovariectomized mice. Metabolism 53:942–948CrossRefGoogle Scholar
  93. Wu XT, Wang B, Wei JN (2009) Coumestrol promotes proliferation and osteoblastic differentiation in rat bone marrow stromal cells. J Biomed Mater Res B Appl Biomater 90:621–628Google Scholar
  94. Xie F, Wu CF, Zhang Y, Yao XS, Cheung PY, Chan AS, Wong MS (2005) Increase in bone mass and bone strength by Sambucus williamsii HANCE in ovariectomized rats. Biol Pharm Bull 28:1879–1885CrossRefGoogle Scholar
  95. Xu X, Harris KS, Wang HJ, Murphy PA, Hendrich S (1995) Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 125:2307–2315Google Scholar
  96. Yamaguchi M, Sugimoto E (2000) Stimulatory effect of genistein and daidzein on protein synthesis in osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase. Mol Cell Biochem 214:97–102CrossRefGoogle Scholar
  97. Yamaguchi K, Shinohara C, Kojima S, Sodeoka M, Tsuji T (1999) (2E,6R)-8-hydroxy-2,6-dimethyl-2-octenoic acid, a novel anti-osteoporotic monoterpene, isolated from Cistanche salsa. Biosci Biotechnol Biochem 63:731–735CrossRefGoogle Scholar
  98. Yen ML, Su JL, Chien CL, Tseng KW, Yang CY, Chen WF, Chang CC, Kuo ML (2005) Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts. Mol Pharmacol 68:1061–1073CrossRefGoogle Scholar
  99. Yin J, Tezuka Y, Kouda K, Tran QL, Miyahara T, Chen Y, Kadota S (2004a) Antiosteoporotic activity of the water extract of Dioscorea spongiosa. Biol Pharm Bull 27:583–586CrossRefGoogle Scholar
  100. Yin J, Tezuka Y, Kouda K, Tran QL, Miyahara T, Chen Y, Kadota S (2004b) In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin. Planta Med 70:220–226CrossRefGoogle Scholar
  101. Yin J, Han N, Liu Z, Song S, Kadota S (2010) The in vitro antiosteoporotic activity of some glycosides in Dioscorea spongiosa. Biol Pharm Bull 33:316–320CrossRefGoogle Scholar
  102. Yuan B, Zhen H, Jin Y, Xu L, Jiang X, Sun S, Li C, Xu H (2012) Absorption and plasma disposition of genistin differ from those of genistein in healthy women. J Agric Food Chem 60:1428–1436CrossRefGoogle Scholar
  103. Zhang Y, Li XL, Lai WP, Chen B, Chow HK, Wu CF, Wang NL, Yao XS, Wong MS (2007) Anti-osteoporotic effect of Erythrina variegata L. in ovariectomized rats. J Ethnopharmacol 109:165–169CrossRefGoogle Scholar
  104. Zhang Y, Li XL, Yao XS, Wong MS (2008) Osteogenic activities of genistein derivatives were influenced by the presence of prenyl group at ring A. Arch Pharm Res 31:1534–1539CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Food Science and BiotechnologyNational Chung Hsing UniversityTaichungTaiwan
  2. 2.Department of Biochemical Science and Technology, College of Life ScienceNational Taiwan UniversityTaipeiTaiwan

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