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Influence of ferutinin on bone metabolism in ovariectomized rats. I: role in preventing osteoporosis

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Abstract

Phytoestrogens play a role in maintaining bone mass in the post-menopausal period for their putative function as osteoprotective agents. The aim of the present study was to investigate the influence of Ferutinin, a phytoestrogen found in the plants of Ferula genus, on bone loss in ovariectomized rats. Such an animal model can simulate the various clinical syndromes deriving from osteoporosis. The effect of the daily oral administration of ferutinin to ovariectomized rats (dosed at 2 mg/kg per day for 30 and 60 days) was compared to that of estradiol benzoate (subcutaneously administered at the dose of 1.5 μg/rat twice a week). After the sacrifice, histomorphometrical analyses were performed on trabecular bone of L4–L5 vertebrae and distal femoral metaphysis, as well as on cortical bone of femoral diaphysis; biochemical parameters (bone mineral components and markers) were also evaluated from the rat serum. The histomorphometrical analyses of trabecular and cortical bone from lumbar vertebrae and femur showed that ferutinin has the same antiosteoporotic effect of estradiol benzoate on bone mass, and in some cases is even stronger. This fact suggests that it could prevent osteoporosis caused by severe estrogen deficiency in ovariectomized rats. The possibility of using ferutinin as an alternative to the commonly employed hormonal replacing therapy in post-menopausal women is discussed.

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References

  1. Riggs BL, Melton LJ (1986) Involutional osteoporosis. N Engl J Med 314:1676–1686

    PubMed  CAS  Google Scholar 

  2. Riggs BL, Khosla S, Melton LJ (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302

    Article  PubMed  CAS  Google Scholar 

  3. Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, Schatzkin A, Schairer C (2002) Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 288:334–341

    Article  PubMed  CAS  Google Scholar 

  4. Beral V (2003) Million women study collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 362:1160

    Article  Google Scholar 

  5. Occhiuto F, De Pasquale R, Guglielmo G, Palumbo DR, Zangla G, Samperi S, Renzo A, Circosta C (2007) Effects of phytoestrogenic isoflavones from red clover (Trifolium pratense L.) on experimental osteoporosis. Phytother Res 21:130–134

    Article  PubMed  CAS  Google Scholar 

  6. Clifton-Bligh PB, Baber RJ, Fulcher GR (2001) The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 8:259–265

    Article  PubMed  CAS  Google Scholar 

  7. Hümpel M, Isaksson P, Schaefer O, Kaufmann U, Ciana P, Maggi A, Schleuning WD (2005) Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with minimal trophic effects on the uterus. J Steroid Biochem Mol Biol 97:299–305

    Article  PubMed  CAS  Google Scholar 

  8. Wuttke W, Seidlová-Wuttke D, Gorkow C (2003) The Cimicifuga preparation BNO 1055 vs conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas 44:S67–S77

    Article  PubMed  Google Scholar 

  9. Mei J, Yeung SS, Kung AW (2001) High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 86:5217–5221

    Article  PubMed  CAS  Google Scholar 

  10. Arjmandi BH, Alekel L, Hollis BW, Amin D, Stacewicz-Sapuntzakis M, Guo P, Kukreja SC (1996) Dietary soy bean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 126:161–167

    PubMed  CAS  Google Scholar 

  11. Deyhim F, Stoecker BJ, Brusewitz GH, Arjmandi BH (2003) The effects of estrogen depletion and isoflavones on bone metabolism in rats. Nutr Res 23:23–30

    Article  Google Scholar 

  12. Abourashed EA, Galal AM, El-Feraly FS, Khan IA (2001) Separation and quantification of the major daucane esters of Ferula hermonis by HPLC. Planta Med 67:681–682

    Article  PubMed  CAS  Google Scholar 

  13. Ikeda K, Arao Y, Otsuka H, Nomoto S, Horiguchi H, Kato S, Kayama F (2002) Terpenoids found in the umbelliferae family act as agonists/antagonists for ERα and ERβ: differential transcription activity between ferutinin-liganded ERα and ERβ. Biochem Biophys Res Commun 291:354–360

    Article  PubMed  CAS  Google Scholar 

  14. Appendino G, Spagliardi P, Cravotto G, Pocock V, Milligan S (2002) Daucane phytoestrogens: a structure–activity study. J Nat Prod 65:612–615

    Google Scholar 

  15. Singh MM, Agnihotri A, Garg SN, Agarwal SK, Gupta DN, Keshri G, Kamboj VP (1988) Antifertility and hormonal properties of certain carotene sesquiterpenes of Ferula jaeschkeana. Planta Med 54:492–494

    Article  PubMed  CAS  Google Scholar 

  16. Zanoli P, Rivasi M, Zavatti M, Brusiani F, Vezzalini F, Baraldi M (2005) Activity of single components of Ferula hermonis on male rat sexual behavior. Int J Impot Res 17:513–518

    Article  PubMed  CAS  Google Scholar 

  17. Zavatti M, Montanari C, Zanoli P (2006) Role of ferutinin in the impairment of female sexual function by Ferula hermonis. Physiol Behav 89:656–661

    Article  PubMed  CAS  Google Scholar 

  18. Wronski TJ, Yen CF (1991) The ovariectomized rat as an animal model for postmenopausal bone loss. Cells Mater Suppl 1:69–74

    Google Scholar 

  19. Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191

    Article  PubMed  CAS  Google Scholar 

  20. Comelekoglu U, Bagis S, Yalin S, Ogenler O, Yildiz A, Sahin NO, Oguz I, Hatungil R (2006) Biomechanical evaluation in osteoporosis: ovariectomized rat model. Clin Reumathol 26:380–384

    Article  Google Scholar 

  21. Einhorn T (1992) Bone strength: the bottom line. Calcif Tissue Int 51:333–339

    Article  PubMed  CAS  Google Scholar 

  22. Garn SM (1975) Bone loss and aging. In: Goldman R, Rockstein M (eds) The physiology and pathology of human aging. Academic Press, New York, p 39

    Google Scholar 

  23. Riis BJ, Rodbro P, Christiansen C (1986) The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis. Calcif Tissue Int 38:18–22

    Article  Google Scholar 

  24. Fanti P, Monier-Faugere MC, Geng Z, Schmidt J, Morris PE, Cohen D, Malluche HH (1998) The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int 8:274–281

    Article  PubMed  CAS  Google Scholar 

  25. Wronski TJ, Schenck PA, Cintron M, Walsh CC (1987) Effect of body weight on osteopenia in ovariectomized rats. Calcif Tiss Int 40:155–159

    Article  CAS  Google Scholar 

  26. Wegorzewska IN, Walters K, Weiser MJ, Cruthirds DF, Ewell E, Larco DO, Handa RJ, Wu TJ (2008) Ovariectomy weight gain in female rats is reversed by estrogen receptor alpha agonist, propylpyrazoletriol. Am J Obstet Gynecol 199:67.e1–67.e5

    Article  CAS  Google Scholar 

  27. Kraichely DM, Sun J, Katzenellenbogen JA, Katzenellenbogen BS (2000) Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-alpha and estrogen receptor-beta: correlations with biological character and distinct differences among SRC coactivator family members. Endocrinology 141:3534–3545

    Article  PubMed  CAS  Google Scholar 

  28. Stauffer SR, Coletta CJ, Tedesco R, Nishiguchi G, Carlson K, Sun J, Katzenellenbogen BS, Katzenellenbogen JA (2000) Pyrazole ligands: structure–affinity/activity relationships and estrogen receptor-alpha-selective agonists. J Med Chem 43:4934–4947

    Article  PubMed  CAS  Google Scholar 

  29. Evans DB, Bunning RAD, Russell RGG (1990) The effect of recombinant human interleukine-1β on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alcalin phosphatase by osteoblast-like cells derived from human bone. Biochem Biophys Res Commun 166:208–216

    Article  PubMed  CAS  Google Scholar 

  30. Nian H, Qin LP, Zhang QY, Zheng HC, Yu Y, Huang BK (2006) Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats. J Ethnopharmacol 108:96–102

    Article  PubMed  Google Scholar 

  31. Frost HM (1987) Bone “mass” and the “mechanostat”: a proposal. Anat Rec 219:1–9

    Article  PubMed  CAS  Google Scholar 

  32. Pan W, Quarles LD, Song LH, Yu YH, Jiao C, Tang HB, Jiang CH, Deng HW, Li YJ, Zhou HH, Xiao ZS (2005) Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. J Cell Biochem 94:307–316

    Article  PubMed  CAS  Google Scholar 

  33. Liao QC, Xiao ZS, Qin YF, Zhou HH (2007) Genistein stimulates osteoblastic differentiation via p38 MAPK-Cbfa1 pathway in bone marrow culture. Acta Pharmacol Sin 28:1597–1602

    Article  PubMed  CAS  Google Scholar 

  34. Hertrampf T, Gruca MJ, Seibel J, Laudenbach U, Fritzmeier KH, Diel P (2007) The bone-protective effect of the phytoestrogen genistein is mediated via ERα-dependent mechanisms and strongly enhanced by physical activity. Bone 40:1529–1535

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by 2007 FAR–MARO funds and by Fondazione Cassa di Risparmio of Modena (CARIMO).

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Authors and Affiliations

  1. Section of Human Anatomy, Department of Anatomy and Histology, University of Modena and Reggio Emilia, Via del Pozzo 71 (Area policlinico), 41100, Modena, Italy

    Carla Palumbo, Marzia Ferretti, Laura Bertoni, Francesco Cavani, Elisa Resca, Manuela Zavatti & Augusta Benelli

  2. Institute of Clinic Pathology, Toxicology and Advanced Diagnostics, USL Modena, Modena, Italy

    Barbara Casolari

  3. Section of Pharmacology, Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy

    Gianluca Carnevale, Caterina Montanari & Paola Zanoli

Authors
  1. Carla Palumbo
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  2. Marzia Ferretti
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  3. Laura Bertoni
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  4. Francesco Cavani
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  5. Elisa Resca
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  6. Barbara Casolari
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  7. Gianluca Carnevale
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  8. Manuela Zavatti
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  9. Caterina Montanari
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  10. Augusta Benelli
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  11. Paola Zanoli
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Corresponding author

Correspondence to Carla Palumbo.

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Palumbo, C., Ferretti, M., Bertoni, L. et al. Influence of ferutinin on bone metabolism in ovariectomized rats. I: role in preventing osteoporosis. J Bone Miner Metab 27, 538–545 (2009). https://doi.org/10.1007/s00774-009-0070-x

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  • DOI: https://doi.org/10.1007/s00774-009-0070-x

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