Biological Trace Element Research

, Volume 187, Issue 1, pp 172–180 | Cite as

Du-Zhong (Eucommia ulmoides Oliv.) Cortex Extract Alleviates Lead Acetate-Induced Bone Loss in Rats

  • Shanshan Qi
  • Hongxing ZhengEmail author
  • Chen ChenEmail author
  • Hai Jiang


The purpose of this study was to evaluate the protective effect of Du-Zhong cortex extract (DZCE) on lead acetate-induced bone loss in rats. Forty female Sprague-Dawley rats were randomly divided into four groups: group I (control) was provided with distilled water. Group II (PbAc) received 500 ppm lead acetate in drinking water for 60 days. Group III (PbAc+DZCE) received 500 ppm lead acetate in drinking water, and given intragastric DZCE (100 mg/kg body weight) for 60 days. Group IV (DZCE) was given intragastric DZCE (100 mg/kg body weight) for 60 days. The bone mineral density, serum biochemical markers, bone histomorphology, and bone marrow adipocyte parameters were analyzed using dual-energy X-ray absorptiometry, biochemistry, histomorphometry, and histopathology, respectively. The results showed that the lumbar spine and femur bone mineral density was significantly decreased in PbAc group compared with the control (P < 0.05); however, this decrease was inhibited by the intake of Du-Zhong cortex extract (P < 0.05, vs. PbAc group; P > 0.05, vs. control and DZCE group). Serum calcium and serum phosphorus in the PbAc+DZCE group were greater than that in the PbAc group (P < 0.05). The PbAc group had higher ALP, osteocalcin, and RANKL than the control group (P < 0.01), and they were significantly lower in the PbAc+DZCE group compared with the PbAc group. There were no significant differences of ALP, osteocalcin, and RANKL among the PbAc+DZCE, control, and DZCE groups (P > 0.05). Serum OPG and OPG/RANKL ration were significantly higher in the PbAc+DZCE group than that in the PbAc group (P < 0.05). The bone histomorphometric analyses showed that bone volume and trabecular thickness in the femoral trabecular bone were significantly lower in the PbAc group than that in the control group, but those were restored in the PbAc+DZCE groups. The bone marrow adipocyte number, percent adipocyte volume per tissue volume (AV/TV), and mean adipocyte diameter were significantly increased in the PbAc group compared to the control (P < 0.01), and those were restored in the PbAc+DZCE group. The differences of those parameters between PbAc+DZCE, DZCE, and the control group were not significant. The results above indicate that the Du-Zhong cortex extract has protective effects on both stimulation of bone formation and suppression of bone resorption in lead-exposed rats, therefore, Du-Zhong cortex extract has the potential to prevent or treat osteoporosis resulting from lead expose.


Eucommia ulmoides Oliv Lead BMD Bone histomorphology Rats 


Funding Information

This work was supported by the High-end Foreign Expert Recruitment Programme of State Administration of Foreign Experts Affairs (GDT20176100048), Qinling-Bashan Mountains Bioresources Comprehensive Development, Collaborative Innovation Center Research Funds QBXT-Z(P)-15-25, Shaanxi Science and Technology Coordinating Innovation Engineering Program (2015KTTSSF01-03, 2015HBGC-18), the Key Project of Agricultural Science and Technology of Shaanxi Province (2017NY-082), Postdoctoral Program in Shaanxi University of Technology (SLGBH16-03), and Research Project of Shaanxi Provincial Education Department (17JK0153).

Compliance with Ethical Standards

Conflict of Interest

The authors certify that there is no conflict of interest to declare.


  1. 1.
    Conti M, Terrizzi A, Lee C et al (2012) Effects of lead exposure on growth and bone biology in growing rats exposed to simulated high altitude. Bull Environ Contam Toxicol 88(6):1033–1037CrossRefGoogle Scholar
  2. 2.
    Monir AU, Gundberg CM, Yagerman SE, van der Meulen MCH, Budell WC, Boskey AL, Dowd TL (2010) The effect of lead on bone mineral properties from female adult C57/BL6 mice. Bone 47:888–894CrossRefGoogle Scholar
  3. 3.
    Keson T, Thomas AG, Karen BR et al (2008) Associations of bone mineral density and lead levels in blood, tibia, and patella in urban-dwelling women. Environ Health Perspect 116(6):784–790CrossRefGoogle Scholar
  4. 4.
    Escribano A, Revilla M, Hernández ER, Seco C, González-Riola J, Villa LF, Rico H (1997) Effect of lead on bone development and bone mass: a morphometric, densitometric, and histomorphometric study in growing rats. Calcified Tissue Int 60(2):200–203CrossRefGoogle Scholar
  5. 5.
    Potula V, Kleinbaum D, Kaye W (2006) Lead exposure and spine bone mineral density. J Occup Environ Med 48:556–564CrossRefGoogle Scholar
  6. 6.
    Chen X, Wang K, Wang Z, Gan C, He P, Liang Y, Jin T, Zhu G (2014) Effects of lead and cadmium coexposure on bone mineral density in a Chinese population. Bone 63:76–80CrossRefGoogle Scholar
  7. 7.
    Campbell JR, Rosier RN, Novotny L, Puzas JE (2004) The association between environmental lead exposure and bone density in children. Environ Health Perspect 112:1200–1203CrossRefGoogle Scholar
  8. 8.
    Campbell JR, Auinger P (2007) The association between blood lead levels and osteoporosis among adults—results from the third National Health and Nutrition Examination Survey (NHANES III). Environ Health Perspect 115:1018–1022CrossRefGoogle Scholar
  9. 9.
    Beier EE, Maher JR, Sheu TJ, Cory-Slechta DA, Berger AJ, Zuscik MJ, Puzas JE (2013) Heavy metal lead exposure, osteoporotic-like phenotype in an animal model, and depression of Wnt signaling. Environ Health Perspect 121(1):97–104CrossRefGoogle Scholar
  10. 10.
    Conti MI, Bozzini C, Facorro G et al (2012) Lead bone toxicity in growing rats exposed to chronic intermittent hypoxia. Bull Environ Contam Toxicol 89:693–698CrossRefGoogle Scholar
  11. 11.
    Zhang R, Liu ZG, Li C, Hu SJ, Liu L, Wang JP, Mei QB (2009) Du-Zhong (Eucommia ulmoides Oliv.) cortex extract prevent OVX-induced osteoporosis in rats. Bone 45(3):553–559CrossRefGoogle Scholar
  12. 12.
    Kim B, Lim DW, Song J et al (2012) Anti-osteoporotic effect of Eucommia ulmoides cortex in ovariectomized rats. Planta Med 78(11):1130–1130Google Scholar
  13. 13.
    Li HW, Deng JG, Du ZC et al (2013) Protective effects of mangiferin in subchronic developmental lead-exposed rats. Biol Trace Elem Res 152:233–242CrossRefGoogle Scholar
  14. 14.
    Nagaraja H, Tan J, Srikumar C et al (2010) Protective effects of Etlingera elatior extract on lead acetate-induced changes in oxidative biomarkers in bone marrow of rats. Food and Chem Toxicol 48:2688–2694CrossRefGoogle Scholar
  15. 15.
    Qi SS, Zheng HX (2017) Combined effects of phytoestrogen genistein and silicon on ovariectomy-induced bone loss in rat. Biol Trace Elem Res 177(2):281–285CrossRefGoogle Scholar
  16. 16.
    Syed FA, Oursler MJ, Hefferanm TE, Peterson JM, Riggs BL, Khosla S (2008) Effects of estrogen therapy on bone marrow adipocytes in post-menopausal osteoporotic women. Osteoporos Int 19:1323–1330CrossRefGoogle Scholar
  17. 17.
    Li GW, Xu Z, Chang SX (2014) Influence of early zoledronic acid administration on bone marrow fat in ovariectomized rats. Endocrinology 155(12):4731–4738CrossRefGoogle Scholar
  18. 18.
    Raafat BM, Hassan NS, Aziz SW (2012) Bone mineral density (BMD) and osteoporosis risk factor in Egyptian male and female battery manufacturing workers. Toxicol Ind Health 28(3):245–249CrossRefGoogle Scholar
  19. 19.
    Nilima N, Dongre AN, Suryakar AJ et al (2013) Biochemical effects of lead exposure on battery manufacture workers with reference to blood pressure, calcium metabolism and bone mineral density. Ind J Clin Biochem 28(1):65–70CrossRefGoogle Scholar
  20. 20.
    Bassem MR, Nahed SH (2012) Bone mineral density (BMD) and osteoporosis risk factor in Egyptian male and female battery manufacturing workers. Toxicol Ind Health 28(3):245–252CrossRefGoogle Scholar
  21. 21.
    Lee BK, Kim Y (2012) Association between bone mineral density and blood lead level in menopausal women: analysis of 2008–2009 Korean national health and nutrition examination. Environ Res 115(5):59–65PubMedPubMedCentralGoogle Scholar
  22. 22.
    Pollack AZ, Mumford SL, Wactawski-Wende J, Yeung E, Mendola P, Mattison DR, Schisterman EF (2013) Bone mineral density and blood metals in premenopausal women. Environ Res 120(1):76–81CrossRefGoogle Scholar
  23. 23.
    Gade TP, Motley MW, Beattie BJ, Bhakta R, Boskey AL, Koutcher JA, Mayer-Kuckuk P (2011) Imaging of alkaline phosphatase activity in bone tissue. PLoS One 6(7):e22608CrossRefGoogle Scholar
  24. 24.
    Arimandi BH, Birnbaum RS, Juma S et al (2000) The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms. Calcified Tissue Int 66:61–65CrossRefGoogle Scholar
  25. 25.
    Hamilton JD, OpFlaherty EJ (1999) Influence of lead on mineralization during bone growth. Fundam Appl Toxicol 26(2):265–271CrossRefGoogle Scholar
  26. 26.
    Enjuanes A, Ruiz-Gaspà S, Peris P et al (2010) The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts. Endocrine 37(2):322–328CrossRefGoogle Scholar
  27. 27.
    Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 15(2):139–146CrossRefGoogle Scholar
  28. 28.
    Hao Y, Gao R, Lu B, Ran Y, Yang Z, Liu J, Li R (2018) Ghrelin protects against depleted uranium-induced bone damage by increasing osteoprotegerin/RANKL ratio. Toxicol Appl Pharm 343(15):62–70CrossRefGoogle Scholar
  29. 29.
    Liu JM, Zhao HY, Ning G, Zhao YJ, Chen Y, Zhang Z, Sun LH, Xu MY, Chen JL (2005) Relationships between the changes of serum levels of OPG and RANKL with age, menopause, bone biochemical markers and bone mineral density in Chinese women aged 20-75. Calcified Tissue Int 76(1):1–6CrossRefGoogle Scholar
  30. 30.
    Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, Baron R, Rosen CJ, Bouxsein ML (2010) Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res 25(9):2078–2088CrossRefGoogle Scholar
  31. 31.
    Pino AM, Miranda M, Figueroa C et al (2016) Qualitative aspects of bone marrow adiposity in osteoporosis. Front Endocrinol 7(3):1–6Google Scholar
  32. 32.
    Maddalozzo GF, Turner RT, Edwards CH et al (2009) Alcohol alters whole body composition, inhibits bone formation, an increases bone marrow adiposity in rats. Osteoporos Int 20(9):1529–1538CrossRefGoogle Scholar
  33. 33.
    Botolin S, Mccabe LR (2007) Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology 148(1):198–205CrossRefGoogle Scholar
  34. 34.
    Cornish JL, Wang T, Lin JM (2018) Role of marrow adipocytes in regulation of energy metabolism and bone homeostasis. Curr Osteoporos Rep 16(2):116–122CrossRefGoogle Scholar
  35. 35.
    Cohen A, Dempster DW, Stein EM, Nickolas TL, Zhou H, McMahon DJ, Müller R, Kohler T, Zwahlen A, Lappe JM, Young P, Recker RR, Shane E (2012) Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 97(8):2782–2791CrossRefGoogle Scholar
  36. 36.
    Yang Y, Luo X, Yan F, Jiang Z, Li Y, Fang C, Shen J (2015) Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy. Skelet Radiol 44(10):1499–1505CrossRefGoogle Scholar
  37. 37.
    Li BH, Liu H, Jia SN (2015) Zinc enhances bone metabolism in ovariectomized rats and exerts anabolic osteoblastic/adipocytic marrow effects ex vivo. Biol Trace Elem Res 163(1):202–207CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Vitamin D Research InstituteShaanxi University of TechnologyHanzhongChina
  2. 2.College of Biological Science and EngineeringShaanxi University of TechnologyHanzhongChina
  3. 3.Chinese-German Joint Laboratory for Natural Product ResearchShaanxi University of TechnologyHanzhongChina

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