Archives of Pharmacal Research

  • 제27권1호
  • /
  • Pages.99-105
  • /
  • 2004
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Isoflavones Extracted from Sophorae fructus Upregulate IGF-1 and TGF-$\beta$ and Inhibit Osteoclastogenesis in Rat Born Marrow Cells

  • Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Won, Tae-Joon (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Kang, Hee-Cheol (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
  • 발행 : 2004.01.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Isoflavones have been a central subject in research on the natural phytoestrogens found in Leguminosae. Their effects on bone formation and remodeling are important in that they can act like estrogen by binding on estrogen receptors on the target cell surface. We, therefore, believed that isoflavones may help in the treatment of patients with estrogen deficiency disease such as estrogen replacement therapy (ERT) for osteoporosis. As commonly known, osteoporosis is one of the hormonal deficiency diseases, especially in menopausal women. When estrogen is no longer produced in the body a remarkable bone remodeling process occurs, and the associated events are regulated by growth factors in the osteoblast lineage. In the present study, we investigated whether isoflavones (Isocal) extracted from Sophorae fructus affect the growth factors IGF-I and TGF-$\beta$ that have been known to be related with bone formation. In the study, we found that the active control (PIII) effectively enhanced the level of nitric oxide (NO) and growth factors, and thereby inhibited osteoclastogenesis. The most efficient concentration was $10^{-8}$% within five days, whereas the comparative control (soybean isoflavone) was not as effective even at a lower concentration. In conclusion, the products which contain enriched glucosidic isoflavone and nutrient supplements such as shark cartilage and calcium can be used for osteoporosis therapy by enhancing the production of IGF-I and TGF-$\beta$. Furthermore, the NO produced through endothelial constitutive NO synthase (ecNOS) may playa role in inhibiting bone reabsorption.

키워드

참고문헌

  1. Adlercreutz, H., Phyto-oestrogens and cancer. Lancet Oncology, 3, 364-373 (2002) https://doi.org/10.1016/S1470-2045(02)00777-5
  2. Aguirre, J., Buttery, L., O'Shaughnessy, M., Afzal, F., Fernandez de Marticorena, I., Hukkanen, M., Huang, P., Manlntyre, I., and Polak, J., Endothelial nitric oxide synthase gene-deficient mice demonstrate marked retardation in postnatal bone formation, reduced bone volume, and defects in osteoblast maturation and activity. Am. J. Pathol., 158(1), 247-257 (2001) https://doi.org/10.1016/S0002-9440(10)63963-6
  3. Amonkar, M. M. and Mody, R., Developing profiles of postmenopausal women being prescribed oestrogen therapy to prevent osteoporosis. J. community Health, 27, 335-350 (2002) https://doi.org/10.1023/A:1019836610275
  4. Armpur, K. E. and Ralston, S. H., Estrogen upregulates endothelial constitutive nitric oxide synthase expression in human osteoblast-like cells. Endocrinology, 139, 799-802 (1998) https://doi.org/10.1210/en.139.2.799
  5. Aubin, J. E. and Bonnelye, E., Osteoprotegerin and its ligand: A new paradigm for regulation of osteoclastogenesis and bone reabsorption. Osteoporos. Int., 11, 905-913 (2000) https://doi.org/10.1007/s001980070028
  6. Baylink, D. J., Finkelman, R. D., and Moban, S., Growth factors to stimulate bone formation. J. Bone Miner. Res., 2(8), S565-S572 (1993)
  7. Brancli, M. L., Hukkanen, M., Umeda, T., Moradi-Bidhendi, N., Bianchi, S., Gross, S. S., Polak, J. M., and Macintyre, I. Bidirectional regulation of osteoclast function by nitric oxide synthesis isofors. Proc. Natl. Acad. Sci. USA, 92, 2954-2958 (1995) https://doi.org/10.1073/pnas.92.7.2954
  8. Bilezikian, J. P., Morishima, A., Bell, J., and Grumbach, M.M., Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. N. Engl. J. Med., 339, 599-603 (1998) https://doi.org/10.1056/NEJM199808273390905
  9. Centrella, M., McCarthy, T., and Cannalis, E., Transforming growth factor-beta and remodeling of bone. J. Bone Joint Surg. Am., 73, 1418-1428 (1991) https://doi.org/10.2106/00004623-199173090-00022
  10. Duncan, A. M., Phipps, W. R., and Kurzer, M. S., Phyto-oestrogen. Best Practice & Research Clinical Endocrinology and Metabolism, 17, 253-271 (2003) https://doi.org/10.1016/S1521-690X(02)00103-3
  11. Eastel, R., Treatment of postmenopausal osteoporosis. N. Engl. J. Med., 338, 736-746 (1998) https://doi.org/10.1056/NEJM199803123381107
  12. Greenfield, E. M., Bi, Y., and Miyauchi, A., Regulation of osteoclast activity. Life Sicence, 65, 1087-1102 (1999) https://doi.org/10.1016/S0024-3205(99)00156-3
  13. Joo, S. S., Chang, J. K., Park, J. H., Kang, H. C., and Lee, D. I., Immuno activation of lectin-conjugated praecoxin A on IL-6, IL-12 expression. Arch. Pharm. Res., 25, 954-963 (2002) https://doi.org/10.1007/BF02977019
  14. Kanamaru, Y., Takada, T., Saura, R., and Mizuno. K., Effect of nitric oxide on mouse clonal osteogenic cell, MC3T3-E1, proliferation in vitro. Kobe J. Med. Sci., 47, 1-11 (2001)
  15. Klein-Nulend, J., Helfrich, M. H., Sterck, J. G., MacPherson, H., Joldersma, M., Raison, S. H., Semeins, C. M., and Burger, E. H, Nitric oxide response to shear stress by human bone cell culture is endothelial nitric oxide synthase dependant. Biochem. Biophys. Res. Commun., 250, 108-114 (1998) https://doi.org/10.1006/bbrc.1998.9270
  16. Lian, J., Stein, G., Canalis, E., Robey, P., and Boskey, A., Bone formation: osteoblast lineage cells, growth factors, matrix proteins, and the mineralization process in. In Favus M, ed. Primer on the metabolic bone disease and disorders of mineral metabolism. Vol. 1. Philadelphia: Lippincott Williams and Wilkins (1999)
  17. Messina, M. and Messina, V., Soyfood, soybean isoflavone, abd bone health: a brief overview. J. Renal Nutrition, 10, 63-68 (2000) https://doi.org/10.1016/S1051-2276(00)90001-3
  18. Mundy, G., Bone modeling. In: Favus M, ed. Primer on the metabolic bone disease and disorders of mineral metabolism. Vol. 1. 4th ed. Philadelphia, Lippincott Williams and Wilkins (1999)
  19. Mundy, G. R., Bone remodeling and its disorders (ed. M. Dunits). London, UK (1995)
  20. Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Yano, K., Morinaga, T., and Higashio, K., RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem. Biophys. Res. Commun., 253, 395-400 (1998) https://doi.org/10.1006/bbrc.1998.9788
  21. Pacifici, R., Cytokines, estrogen and postmenopausal osteoporosis-the second decade. Endocrinology, 139, 2659-2661 (1998) https://doi.org/10.1210/en.139.6.2659
  22. Raisz, L. G., The osteoporosis revolution. Ann. Intern. Med., 126, 458-462 (1997) https://doi.org/10.7326/0003-4819-126-6-199703150-00007
  23. Riggs, B. L., Khosia, S., and Melton, L. J., 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, 763-773 (1998) https://doi.org/10.1359/jbmr.1998.13.5.763
  24. Setchell, K. D., Abstract presented at: Second international symposium on the role of soy in preventing and treating chronic disease. Brussel Belgium (1996)
  25. Swolin-Eide, D. and Ohlsson, C., Effects of cortisol on the expression of interleukin-6 and interleukin-$1{\beta}$ in human osteoblast like cells. J. Endocrinology, 156, 107-114 (1998) https://doi.org/10.1677/joe.0.1560107
  26. Udagawa, N., Takahashi, N., Matsuzaki, K., Jimi, E., Tsurukai, T., Itoh, K., Nakagawa, H., Yasuda, H., Goto, M., Tsuda, E., Higashio, K., Martin, T. J., and Suda, T., Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. Bone, 5, 517-523 (1999)
  27. van't Hof, R. J. and Ralston, S. H., Nitric oxide and bone. Immunology, 103, 255-261 (2001) https://doi.org/10.1046/j.1365-2567.2001.01261.x
  28. Warren, M. P., Shortle, B., and Dominguez, J. E., Use of alternative therapies in menopause. Best Practice & Research Clinical Obstetrics and Gynaecology, 16(3), 411-448 (2002) https://doi.org/10.1053/beog.2002.0290
  29. Wimalawansa, S. J., De Marco, G., Gangula, P., and Yallampalli, Nitric oxide donor alleviates ovariectomy-induced bone loss. Bone, 18, 301-304 (1996) https://doi.org/10.1016/8756-3282(96)00005-1
  30. Yamaguchi, M. and Gao, Y. H., Inhibitory effect of genistein on bone reabsorption in tissue culture. Biochem. Phamacol., 55, 71-76 (1998) https://doi.org/10.1016/S0006-2952(97)00402-4