The research progress of plant estrogen genistein in osteoporosis treatment

Abstract

Abstract: Based on the correlative materials of recent 10 year searched from the data base of Google Scholar and Science Direct,the mechanism of anti-osteoporosis, the pharmacological activity of anti-osteoporosis, the pharmacokinetics, drug safety of genistein had been briefly summarized overlaying multiple perspectives. The binding force of genistein to the estrogen receptor α is greater than that to the estrogen receptor β and the primary receptor of its pharmacological activity of anti-osteoporosis is estrogen receptor α.Whatever in vitro or in vivo, all the reports below indicate the anti-osteoporosis ability of genistein is surprising. The pharmacology activity of genistein includes inhibited the ability of bone marrow macrophage translated into to osteoclast , inhibited the proliferation ability of osteoclast , induced the apoptosis of osteoclasts, and promoted the proliferation ability of osteoblast.Therapeutic efficacy of anti-osteoporosis is definite, but the toxic and side effect is less than diphosphonate and teriparatide. Geniste has the potential of becoming the clinical first-line drug in treatment of osteoporosis in the future.

Key words: Genistein, Plant estrogen, Anti-osteoporosis

CLC Number:

R587

LIN Zhong, SUN Yuan, DU You-gong, YANG Jian-miao, LIN Jian-qun. The research progress of plant estrogen genistein in osteoporosis treatment[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(1): 105-111.

References

[1] Devogelaer JP. Glucocorticoid-induced osteoporosis: mechanisms and therapeutic approach[J]. Rheum Dis Clin North Am, 2006,32(4):733-757.
[2] Sambrook PN. Anabolic therapy in glucocorticoid-induced osteoporosis[J]. N Engl J Med,2007, 357(20): 2084-2086.
[3] Wu Q, Bencaz AF, Hentz JG, et al. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies[J]. Osteoporos Int,2012,23(1):365-375.
[4] Dennison E, Cole Z, Cooper C, et al. Diagnosis and epidemiology of osteoporosis[J]. Curr Opin Rheumatol,2005,17(4):456-461.
[5] Brand ML. Natural and synthetic isoflavones in the prevention and treatment of chronic diseases[J]. Osteoporosis International,1996, 6 (Supple1) :317.
[6] Arjmandi BH, Alekei L, Hollis B, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis[J]. J Nutr, 1996,126(1): 161-167.
[7] Gao YH, Yamaguchi M. Inhibitory effect of genistein on osteoclast-like cell formation inmouse marrow cultures[J]. Biochem Pharmacol, 1999,58(5): 767-772.
[8] Sugimoto E, Yamaguchi M. Anabolic effect of genistein in osteoblastic MC3T3-E1 cells[J]. Int J Mol Med,2000, 5(5): 515-520.
[9] Yamaguchi M, Gao YH. Anabolic effect of daidzein on cortical bone in tissue culture: Comparison with genistein effect[J].Molecular and Cellular Biochemistry, 1999,194(1): 93-98.
[10] Li XL, Wang NL, Wong MS, et al. Four new isoflavonoids from the stem bark of Erythrina variegate[J]. Chem Pharm Bull, 2006,54(4):570-573.
[11] Yan Z, Xiao LL, Xin SY, et al. Osteogenic Activities of genistein derivatives were influenced by the presence of prenyl group at ring A[J]. Arch Pharm Res, 2008,31(12):1534-1539.
[12] Ruchun D, Yulin M, Zhifeng S, et al. Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats[J]. J Bone Miner Metab,2008,26(4):342-349.
[13] Zhang Y, Li Q, Wan HY, et al. Genistein and a soy extract differentially affect three-dimensional bone parameters and bone-specific gene expression in ovariectomized mice[J].J Nutr,2009, 139(12):2230-2236.
[14] Ferrettia M, Bertonib L, Cavania F.Structural and histomorphometric evaluations of ferutinin effects on the uterus of ovariectomized rats during osteoporosis treatment[J].Life Sciences,2012,90 (3):161-168.
[15] Catherine A, Schnell JD, Kubas KL, et al. Effects of soy isoflavone consumption on bone structure and milk mineral concentration in a rat model of lactation-associated bone loss[J]. Eur J Nutr,2009,48(2):84-91.
[16] Hyekyung H, Young LH, Jehyun L, et al. Formononetin prevents ovariectomy-induced bone loss in rats[J]. Arch Pharm Res, 2010,33, (4) :625-632.
[17] Rayalam S, Dellafera MA, Clifton A, et al. Synergism between resveratrol and other phytochemicals:Implications for obesity and osteoporosis[J]. Molecular nutrition and food, 2011,55 (8):1177-1185.
[18] Bitto A, Burnett BP, Polito F. Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate[J]. Bri J Pharmacol, 2009, 156(8): 1287-1295.
[19] Dai R, Ma Y, Sheng Z,et al. Effects of genistein on vertebral trabecular bone microstructure, bone mineral density, microcracks, osteocyte density, and bone strength in ovariectomized rats[J]. J Bone Miner Metab, 2008, 26(4): 342-349.
[20] Choi SY, Ha TY, Ahn JY, et al. Estrogenic activities of isoflavones and flavones and their structure-activity relationships[J]. Planta Med, 2008, 74(1): 25-32.
[21] Liu Y, Hu M. Absorption and metabolism of flavonoids in the Caco-2 cell culture model and a perused rat intestinal model[J]. Drug Metab Dispos, 2002, 30(4): 370-377.
[22] Chen J, Lin H, Hu M, Metabolism of flavonoids via enteric recycling: role of intestinal disposition[J] J. Pharmacol Exp Ther,2003, 304(3):1228-1235.
[23] Uwe U, Juergen M, Thomas F, et al. Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein in healthy volunteers[J]. Advances in Therapy, 2005, 22 (1): 65-78.
[24] Marini H, Bitto A, Altavilla D, et al. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study[J].J Clin Endocrinol Metab,2008, 93(12):4787-4796.
[25] Brandi ML. Natural and synthetic isoflavones in the prevention and treatment of chronic diseases [J]. Calcif Tissue Int,1997,61 (Suppl 1): 5-8.
[26] Paech K, Webb P, Kuiper GG. Differential ligand activation of estrogen receptors ER αand ERβ at AP-1 sites [J]. Science , 1997, 277(3):1508 - 1510.
[27] Waters KM, Rickard DJ, Riggs BL, et al. Estrogen regulation of human osteoblast function is determined by the stage of differentiation and the estrogen receptor isoform[J]. J Cell Biochem, 2001, 83(3): 448 -462.
[28] Rickard DG, Monroe TJ, Ruesink S. Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors α and β[J]. J Cell Biochem, 2003, 89(3): 633-646.
[29] Hertrampfa MJ, Grucaa J, Seibela U. The bone-protective effect of the phytoestrogen genistein is mediated via ERα-dependent mechanisms and strongly enhanced by physical activity[J]. Bone, 2007,40(6):1529-1535.
[30] Satoshi U, Masayoshi, Yamaguchi PD. Genistein and zinc synergistically stimulate apoptotic cell death and suppress RANKL signaling-related gene expression in osteoclastic cells[J]. J Cell Biochem, 2007,101(3):529-542.
[31] Matsukawa Y, Marui N, Sakai T, et al. Genistein arrests cell cycle progression at G2M[J]. Cancer Research, 1993, 53(4):1328-1331.
[32] Gao YH, Yamaguchi M. Suppressive effect of genistein on rat bone osteoclasts: apoptosis is induced through Ca²⁺ signaling[J]. Biol Pharm. Bull, 1999, 22(8):805-809.
[33] Yamaguchi M, Gao YH. Inhibitory effect of genistein on bone resorption in tissue culture[J].Biochem Pharmacol,1998,55(1): 71-76.
[34] Rickard, Monroe, Ruesink. Phytoestrogen genistein acts as an estrogen agonist on human osteoblastic cells through estrogen receptors alpha and beta[J]. J Cell Biochem,2003,89(3): 633-646.
[35] Yan Z, Qi L, Hoi YW. Genistein and a Soy Extract Differentially Affect three-dimensional bone parameters and bone-specific gene expression in ovariectomized mice [J]. J Nutr, 2009,139(12): 2230-2236.
[36] Zhang Y, Li Q, Wan HY. Study of the mechanisms by which Sambucus williamsii HANCE extract exert protective effects against ovariectomy-induced osteoporosis in vivo[J]. Osteoporos Int, 2010, 22 (2): 703-709.
[37] Van STP. The pathogenesis, epidemiology and management of glucocorticoid-inducedosteoporosis [J]. Calcif Tissue Int,2006,79(3): 129-137.
[38] Civitelli R, Ziambaras K. Epidemiology of glucocorticoid-induced osteoporosis [J]. J Endocrinol Invest, 2008, 31 (7 Suppl): 2-6.
[39] Prinsloo PJJ, Hosking DJ. Alendronate sodium in the management of osteoporosis[J]. J Therap Clin Risk Manag, 2006, 2(3): 235-249.
[40] Wysowski DK, Chang JT. Alendronate and risedronate: reports of severe bone, joint, andmuscle pain[J]. Arch Int Med,2005,165(3): 346-347.