European Journal of Nutrition

, Volume 53, Issue 5, pp 1155–1164 | Cite as

Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis

  • Mélanie Spilmont
  • Laurent Léotoing
  • Marie-Jeanne Davicco
  • Patrice Lebecque
  • Sylvie Mercier
  • Elisabeth Miot-Noirault
  • Paul Pilet
  • Laurent Rios
  • Yohann WittrantEmail author
  • Véronique Coxam
Original Contribution



Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti-inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis.


We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7 % of PG lyophilized mashed totum (OVX PGt), or 9.6 % of PG fresh juice (OVX PGj) or 2.9 % of PG lyophilized mashed peel (OVX PGp).


As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced.


These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status.


Pomegranate Nutritional prevention Osteoporosis Animal model Inflammation Oxidative stress 



Greentech (GREENTECH SA, Saint-Beauzire, France) is kindly acknowledged for providing financial support for this study. The authors are as well grateful to (1) Paul Pilet for his assistance in collecting data of bone micro-architecture from micro-CT, (2) the people from the “Animal lab: Installation Experimentale de Nutrition” who provided every day cares to mice. This study was supported by INRA, UMR 1019, UNH, Clermont-Ferrand, France.

Conflict of interest

The authors have no conflict of interest to declare.


  1. 1.
    Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D, Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T, Kaplan B, Lansky E (2002) Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 71(3):203–217CrossRefGoogle Scholar
  2. 2.
    Murthy KN, Reddy VK, Veigas JM, Murthy UD (2004) Study on wound healing activity of Punica granatum peel. J Med Food 7(2):256–259. doi: 10.1089/1096620041224111 CrossRefGoogle Scholar
  3. 3.
    Johanningsmeier SD, Harris GK (2011) Pomegranate as a functional food and nutraceutical source. Annu Rev Food Sci Technol 2:181–201. doi: 10.1146/annurev-food-030810-153709 CrossRefGoogle Scholar
  4. 4.
    Lansky EP, Newman RA (2007) Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 109(2):177–206. doi: 10.1016/j.jep.2006.09.006 CrossRefGoogle Scholar
  5. 5.
    Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA (2000) Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 48(10):4581–4589CrossRefGoogle Scholar
  6. 6.
    Faria A, Calhau C (2011) The bioactivity of pomegranate: impact on health and disease. Crit Rev Food Sci Nutr 51(7):626–634. doi: 10.1080/10408391003748100 CrossRefGoogle Scholar
  7. 7.
    Stowe CB (2011) The effects of pomegranate juice consumption on blood pressure and cardiovascular health. Complement Ther Clin Pract 17(2):113–115. doi: 10.1016/j.ctcp.2010.09.004 CrossRefGoogle Scholar
  8. 8.
    Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM (2008) Consumption of hydrolyzable tannins-rich pomegranate extract suppresses inflammation and joint damage in rheumatoid arthritis. Nutrition 24(7–8):733–743. doi: 10.1016/j.nut.2008.03.013 CrossRefGoogle Scholar
  9. 9.
    Hadipour-Jahromy M, Mozaffari-Kermani R (2010) Chondroprotective effects of pomegranate juice on monoiodoacetate-induced osteoarthritis of the knee joint of mice. Phytother Res 24(2):182–185. doi: 10.1002/ptr.2880 Google Scholar
  10. 10.
    Balbir-Gurman A, Fuhrman B, Braun-Moscovici Y, Markovits D, Aviram M (2011) Consumption of pomegranate decreases serum oxidative stress and reduces disease activity in patients with active rheumatoid arthritis: a pilot study. Isr Med Assoc J 13(8):474–479Google Scholar
  11. 11.
    Cooper C (2010) Osteoporosis: disease severity and consequent fracture management. Osteoporos Int 21(Suppl 2):S425–S429. doi: 10.1007/s00198-010-1251-0 CrossRefGoogle Scholar
  12. 12.
    Mundy GR (2001) Osteoporosis: pathophysiology and non-pharmacological management. Best Prac Res Clin Rheumatol 15(5):727–745. doi: 10.1053/berh.2001.0190 CrossRefGoogle Scholar
  13. 13.
    Schulman RC, Weiss AJ, Mechanick JI (2011) Nutrition, bone, and aging: an integrative physiology approach. Current osteoporosis reports 9 (4):184–195. doi: 10.1007/s11914-011-0079-7
  14. 14.
    Lacativa PG, Farias ML (2010) Osteoporosis and inflammation. Arq Bras Endocrinol Metabol 54(2):123–132CrossRefGoogle Scholar
  15. 15.
    Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y (2009) Oxidative stress in bone remodelling and disease. Trends Mol Med 15(10):468–477. doi: 10.1016/j.molmed.2009.08.004 CrossRefGoogle Scholar
  16. 16.
    Park EK, Kim MS, Lee SH, Kim KH, Park JY, Kim TH, Lee IS, Woo JT, Jung JC, Shin HI, Choi JY, Kim SY (2004) Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation. Biochem Biophys Res Commun 325(4):1472–1480. doi: 10.1016/j.bbrc.2004.10.197 CrossRefGoogle Scholar
  17. 17.
    Shen CL, Wang P, Guerrieri J, Yeh JK, Wang JS (2008) Protective effect of green tea polyphenols on bone loss in middle-aged female rats. Osteoporos Int 19(7):979–990. doi: 10.1007/s00198-007-0527-5 CrossRefGoogle Scholar
  18. 18.
    Welch A, MacGregor A, Jennings A, Fairweather-Tait S, Spector T, Cassidy A (2012) Habitual flavonoid intakes are positively associated with bone mineral density in women. J Bone Miner Res 27(9):1872–1878. doi: 10.1002/jbmr.1649 CrossRefGoogle Scholar
  19. 19.
    Rosillo MA, Sanchez-Hidalgo M, Cardeno A, Aparicio-Soto M, Sanchez-Fidalgo S, Villegas I, de la Lastra CA (2012) Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol Res 66(3):235–242. doi: 10.1016/j.phrs.2012.05.006 CrossRefGoogle Scholar
  20. 20.
    Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D (2006) Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem 54(3):980–985. doi: 10.1021/jf052005r CrossRefGoogle Scholar
  21. 21.
    Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H (2005) Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int J Cancer 113(3):423–433. doi: 10.1002/ijc.20587 CrossRefGoogle Scholar
  22. 22.
    Lindstedt SL, Schaeffer PJ (2002) Use of allometry in predicting anatomical and physiological parameters of mammals. Lab Anim 36(1):1–19CrossRefGoogle Scholar
  23. 23.
    Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15(3):175–191CrossRefGoogle Scholar
  24. 24.
    Lei Z, Xiaoying Z, Xingguo L (2009) Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats. Int J Exp Pathol 90(5):512–519. doi: 10.1111/j.1365-2613.2009.00661.x CrossRefGoogle Scholar
  25. 25.
    Mori-Okamoto J, Otawara-Hamamoto Y, Yamato H, Yoshimura H (2004) Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J Ethnopharmacol 92(1):93–101. doi: 10.1016/j.jep.2004.02.006 CrossRefGoogle Scholar
  26. 26.
    Ismail T, Sestili P, Akhtar S (2012) Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. J Ethnopharmacol 143(2):397–405. doi: 10.1016/j.jep.2012.07.004 CrossRefGoogle Scholar
  27. 27.
    Viuda-Martos M, Fernández-López J, Pérez-Álvarez JA (2010) Pomegranate and its many functional components as related to human health: a review. Compr Rev Food Sci Food Saf 9(6):635–654CrossRefGoogle Scholar
  28. 28.
    Mastrodi Salgado J, Baroni Ferreira TR, de Oliveira Biazotto F, Dos Santos Dias CT (2012) Increased antioxidant content in juice enriched with dried extract of pomegranate (Punica granatum) Peel. Plant Foods Hum Nutr 67(1):39–43. doi: 10.1007/s11130-011-0264-y CrossRefGoogle Scholar
  29. 29.
    Gautam AK, Bhargavan B, Tyagi AM, Srivastava K, Yadav DK, Kumar M, Singh A, Mishra JS, Singh AB, Sanyal S, Maurya R, Manickavasagam L, Singh SP, Wahajuddin W, Jain GK, Chattopadhyay N, Singh D (2011) Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats. J Nutr Biochem 22(4):318–327. doi: 10.1016/j.jnutbio.2010.02.010 CrossRefGoogle Scholar
  30. 30.
    Monsefi M, Parvin F, Talaei-Khozani T (2011) Effects of pomegranate extracts on cartilage, bone and mesenchymal cells of mouse fetuses. BrJ Nutr 1–8. doi: 10.1017/S0007114511003394
  31. 31.
    Mundy GR (2007) Osteoporosis and inflammation. Nutr Rev 65(12 Pt 2):S147–S151CrossRefGoogle Scholar
  32. 32.
    Muthusami S, Ramachandran I, Muthusamy B, Vasudevan G, Prabhu V, Subramaniam V, Jagadeesan A, Narasimhan S (2005) Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats. Clin Chim Acta 360(1–2):81–86. doi: 10.1016/j.cccn.2005.04.014 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mélanie Spilmont
    • 1
    • 2
    • 3
    • 6
  • Laurent Léotoing
    • 1
    • 2
    • 3
  • Marie-Jeanne Davicco
    • 1
    • 2
    • 3
  • Patrice Lebecque
    • 1
    • 2
    • 3
  • Sylvie Mercier
    • 1
    • 2
    • 3
  • Elisabeth Miot-Noirault
    • 4
    • 5
  • Paul Pilet
    • 6
    • 7
  • Laurent Rios
    • 8
  • Yohann Wittrant
    • 1
    • 2
    • 3
    • 9
    Email author
  • Véronique Coxam
    • 1
    • 2
    • 3
  1. 1.INRA, UMR 1019, UNH, CRNH AuvergneClermont-FerrandFrance
  2. 2.Equipe Alimentation, Squelette et MétabolismesClermont-FerrandFrance
  3. 3.Clermont Université, Université d’AuvergneUnité de Nutrition HumaineClermont-FerrandFrance
  4. 4.Clermont Université, Université d’AuvergneImagerie moléculaire et thérapie vectoriséeClermont-FerrandFrance
  5. 5.Inserm, U 990Clermont-FerrandFrance
  6. 6.Institut National de la Santé et de la Recherche Médicale, UMR S791Laboratoire d’Ingénierie Ostéo-Articulaire et DentaireNantesFrance
  7. 7.Pôle de Recherche et d’Enseignement Supérieur Université Nantes Angers Le Mans, Université de NantesUnité de Formation et de Recherche OdontologieNantesFrance
  8. 8.GREENTECH SA Biopôle Clermont-LimagneSaint-BeauzireFrance
  9. 9.INRA, Equipe ASM, UMR 1019Centre de Recherches INRA de Clermont-Ferrand/TheixClermont-FerrandFrance

Personalised recommendations