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Combined effects of soy isoflavone and lecithin on bone loss in ovariectomized mice

  • Kim, Sang Baek (Osteon Co. Ltd) ;
  • Assefa, Freshet (Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University) ;
  • Lee, Su Jeong (Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University) ;
  • Park, Eui Kyun (Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University) ;
  • Kim, Sung Soo (Osteon Co. Ltd)
  • Received : 2020.09.16
  • Accepted : 2021.02.15
  • Published : 2021.10.01

Abstract

BACKGROUND/OBJECTIVES: Isoflavones (ISFs) are effective in preventing bone loss, but not effective enough to prevent osteoporosis. Mixtures of soy ISF and lecithin (LCT) were prepared and characterized in an attempt to improve the bone loss. MATERIALS/METHODS: The daidzein (DZ) and genistein (GN) solubility in soy ISF were measured using liquid chromatography-mass spectrometry. The change in the crystalline characteristics of soy ISF in LCT was evaluated using X-ray diffraction analysis. Pharmacokinetic studies were conducted to evaluate and compare ISF bioavailability. Animal studies with ovariectomized (OVX) mice were carried out to estimate the effects on bone loss. The Student's t-test was used to evaluate statistical significance. RESULTS: The solubility of DZ and GN in LCT was 125.6 and 9.7 mg/L, respectively, which were approximately 25 and 7 times higher, respectively, than those in water. The bioavailability determined by the area under the curve of DZ for the oral administration (400 mg/kg) of soy ISF alone and the soy ISF-LCT mixture was 13.19 and 16.09 ㎍·h/mL, respectively. The bone mineral density of OVX mice given soy ISF-LCT mixtures at ISF doses of 60 and 100 mg/kg daily was 0.189 ± 0.020 and 0.194 ± 0.010 g/mm3, respectively, whereas that of mice given 100 mg/kg soy ISF was 0.172 ± 0.028 g/mm3. The number of osteoclasts per bone perimeter was reduced by the simultaneous administration of soy ISF and LCT. CONCLUSIONS: The effect of preventing bone loss and osteoclast formation by ingesting soy ISF and LCT at the same time was superior to soy ISF alone as the bioavailability of ISF may have been improved by the emulsification and solvation of LCT. These results suggest the possibility of using the combination of soy ISF and LCT to prevent osteoporosis.

Keywords

Acknowledgement

This research was supported by the startup research program, funded by the Small and Medium Business Administration, Korea (S2645666).

References

  1. Akkawi I, Zmerly H. Osteoporosis: current concepts. Joints 2018;6:122-7. https://doi.org/10.1055/s-0038-1660790
  2. Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S. Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop 2016;7:171-81. https://doi.org/10.5312/wjo.v7.i3.171
  3. Sattui SE, Saag KG. Fracture mortality: associations with epidemiology and osteoporosis treatment. Nat Rev Endocrinol 2014;10:592-602. https://doi.org/10.1038/nrendo.2014.125
  4. Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. N Engl J Med 2003;349:327-34. https://doi.org/10.1056/NEJMoa022464
  5. Vaananen HK, Harkonen PL. Estrogen and bone metabolism. Maturitas 1996;23 Suppl:S65-9. https://doi.org/10.1016/0378-5122(96)01015-8
  6. Hedlund LR, Gallagher JC. The effect of age and menopause on bone mineral density of the proximal femur. J Bone Miner Res 1989;4:639-42. https://doi.org/10.1002/jbmr.5650040423
  7. Chen X, Anderson JJB. Isoflavones and bone: animal and human evidence of efficacy. J Musculoskelet Neuronal Interact 2002;2:352-9.
  8. Picherit C, Chanteranne B, Bennetau-Pelissero C, Davicco MJ, Lebecque P, Barlet JP, Coxam V. Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat. Br J Nutr 2001;85:307-16. https://doi.org/10.1079/BJN2000252
  9. Kim MS, Lee YS. Effects of soy isoflavone and/or estrogen treatments on bone metabolism in ovariectomized rats. J Med Food 2005;8:439-45. https://doi.org/10.1089/jmf.2005.8.439
  10. Kim DW, Yoo KY, Lee YB, Lee KH, Sohn HS, Lee SJ, Cho KH, Shin YK, Hwang IK, Won MH, Kim DW. Soy isoflavones mitigate long-term femoral and lumbar vertebral bone loss in middle-aged ovariectomized mice. J Med Food 2009;12:536-41. https://doi.org/10.1089/jmf.2008.1027
  11. Zheng X, Lee SK, Chun OK. Soy isoflavones and osteoporotic bone loss: a review with an emphasis on modulation of bone remodeling. J Med Food 2016;19:1-14. https://doi.org/10.1089/jmf.2015.0045
  12. Ma DF, Qin LQ, Wang PY, 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;62:155-61. https://doi.org/10.1038/sj.ejcn.1602748
  13. Xiao Y, Zhang S, Tong H, Shi S. Comprehensive evaluation of the role of soy and isoflavone supplementation in humans and animals over the past two decades. Phytother Res 2018;32:384-94. https://doi.org/10.1002/ptr.5966
  14. Mei J, Yeung SS, Kung AW. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001;86:5217-21. https://doi.org/10.1210/jcem.86.11.8040
  15. Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Clin Nutr 2008;27:57-64 https://doi.org/10.1016/j.clnu.2007.10.012
  16. Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, Watanabe S. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr 2010;19:33-42.
  17. Lee H, Choue R, Lim H. Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial. Nutr Res Pract 2017;11:223-31. https://doi.org/10.4162/nrp.2017.11.3.223
  18. Kenny AM, Mangano KM, Abourizk RH, Bruno RS, Anamani DE, Kleppinger A, Walsh SJ, Prestwood KM, Kerstetter JE. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr 2009;90:234-42. https://doi.org/10.3945/ajcn.2009.27600
  19. Brink E, Coxam V, Robins S, Wahala K, Cassidy A, Branca FPHYTOS Investigators. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr 2008;87:761-70. https://doi.org/10.1093/ajcn/87.3.761
  20. Kwak HS, Park SY, Kim MG, Yim CH, Yoon HK, Han KO. Marked individual variation in isoflavone metabolism after a soy challenge can modulate the skeletal effect of isoflavones in premenopausal women. J Korean Med Sci 2009;24:867-73. https://doi.org/10.3346/jkms.2009.24.5.867
  21. Ward WE, Fonseca D. Soy isoflavones and fatty acids: effects on bone tissue postovariectomy in mice. Mol Nutr Food Res 2007;51:824-31. https://doi.org/10.1002/mnfr.200600187
  22. Watkins BA, Reinwald S, Li Y, Seifert MF. Protective actions of soy isoflavones and n-3 PUFAs on bone mass in ovariectomized rats. J Nutr Biochem 2005;16:479-88. https://doi.org/10.1016/j.jnutbio.2005.01.019
  23. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505. https://doi.org/10.1080/07315724.2002.10719248
  24. Watkins BA, Li Y, Lippman HE, Seifert MF. Omega-3 polyunsaturated fatty acids and skeletal health. Exp Biol Med (Maywood) 2001;226:485-97. https://doi.org/10.1177/153537020122600601
  25. Ciriminnaa R, Meneguzzob F, Delisia R, Pagliaro M. Enhancing and improving the extraction of omega-3 from fish oil. Sustain Chem Pharm 2017;5:54-9. https://doi.org/10.1016/j.scp.2017.03.001
  26. Goicoechea E, Brandon EFA, Blokland MH, Guillen MD. Fate in digestion in vitro of several food components, including some toxic compounds coming from omega-3 and omega-6 lipids. Food Chem Toxicol 2011;49:115-24. https://doi.org/10.1016/j.fct.2010.10.005
  27. Ismail A, Bannenberg G, Rice HB, Schutt E, MacKay D. Oxidation in EPA- and DHA-rich oils: an overview. Lipid Technol 2016;28:55-9. https://doi.org/10.1002/lite.201600013
  28. Fricker G, Kromp T, Wendel A, Blume A, Zirkel J, Rebmann H, Setzer C, Quinkert RO, Martin F, Muller-Goymann C. Phospholipids and lipid-based formulations in oral drug delivery. Pharm Res 2010;27:1469-86. https://doi.org/10.1007/s11095-010-0130-x
  29. Uchida R, Chiba H, Ishimi Y, Uehara M, Suzuki K, Kim H, Matsumoto A. Combined effects of soy isoflavone and fish oil on ovariectomy-induced bone loss in mice. J Bone Miner Metab 2011;29:404-13. https://doi.org/10.1007/s00774-010-0234-8
  30. Ihn HJ, Kim JA, Lim S, Nam SH, Hwang SH, Lim J, Kim GY, Choi YH, Jeon YJ, Lee BJ, Bae JS, Kim YH, Park EK. Fermented oyster extract prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis. Nutrients 2019;11:1392-403. https://doi.org/10.3390/nu11061392
  31. Jia L, Xu S, Liu S, Du S, Wu S, Gong J. Polymorphs of daidzein and intermolecular interaction effect on solution crystallization. CrystEngComm 2017;19:7146-53. https://doi.org/10.1039/C7CE01716B
  32. Zhang Z, Huang Y, Gao F, Bu H, Gu W, Li Y. Daidzein-phospholipid complex loaded lipid nanocarriers improved oral absorption: in vitro characteristics and in vivo behavior in rats. Nanoscale 2011;3:1780-7. https://doi.org/10.1039/c0nr00879f
  33. Lee SH, Kim YH, Yu HJ, Cho NS, Kim TH, Kim DC, Chung CB, Hwang YI, Kim KH. Enhanced bioavailability of soy isoflavones by complexation with β-cyclodextrin in rats. Biosci Biotechnol Biochem 2007;71:2927-33. https://doi.org/10.1271/bbb.70296
  34. Deshpande AA, Rhodes CT, Shah NH, Malick AW. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Dev Ind Pharm 1996;22:531-9. https://doi.org/10.3109/03639049609108355
  35. Zhang Y, Na X, Zhang Y, Li L, Zhao X, Cui H. Isoflavone reduces body weight by decreasing food intake in ovariectomized rats. Ann Nutr Metab 2009;54:163-70. https://doi.org/10.1159/000217812