Skip to main content

Advertisement

SpringerLink
Log in

Fructus ligustri lucidi Ethanol Extract Improves Bone Mineral Density and Properties Through Modulating Calcium Absorption-Related Gene Expression in Kidney and Duodenum of Growing Rats

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague–Dawley rats were randomized into four groups and orally administrated for 4 months an AIN-93G formula-based diet supplementing with different doses of FLL ethanol extract (0.40, 0.65, and 0.90 %) or vehicle control, respectively. Then calcium balance, serum level of Ca, P, 25(OH)2D3, 1,25(OH)2D3, osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX-I), and parathyroid hormone, bone microarchitecture, and calcium absorption-related genes expression in duodenum and kidney were analyzed. The results demonstrated that FLL ethanol extract increased BMD of growing rats and improved their bone microarchitecture and mechanical properties. FLL ethanol extract altered bone turnover, as evidenced by increasing a bone formation maker, OCN, and decreasing a bone resorption maker, CTX-I. Intriguingly, both Ca absorption and Ca retention rate were elevated by FLL ethanol extract treatment, possibly through the mechanisms of up-regulating the transcriptions of calcitropic genes in kidney (1α-hydroxylase) and duodenum (vitamin D receptor, calcium transporter calbindin-D9k, and transient receptor potential vanilloid 6). In conclusion, FLL ethanol extract increased bone mass gain and improved bone properties via modulating bone turnover and up-regulating calcium absorption-related gene expression in kidney and duodenum, which could then activate 1,25(OH)2D3-dependent calcium transport in male growing rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Cummings SR, Black DM, Nevitt MC, Browner WS, Cauley JA, Genant HK, Mascioli SR, Scott JC, Seeley DG, Steiger P et al (1990) Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA 263:665–668

    Article  CAS  PubMed  Google Scholar 

  2. Melton LR, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) How many women have osteoporosis? [Perspective]. J Bone Miner Res 7:1005–1010

    Article  PubMed  Google Scholar 

  3. Wang L, Banu J, McMahan CA, Kalu DN (2001) Male rodent model of age-related bone loss in men. Bone 29:141–148

    Article  CAS  PubMed  Google Scholar 

  4. Li ML (1994) Progress in the study on Fructus ligustri lucidi. Zhongguo Zhong Yao Za Zhi 19:504–506

    CAS  PubMed  Google Scholar 

  5. Zhang Y, Lai WP, Leung PC, Wu CF, Yao XS, Wong MS (2006) Effects of Fructus ligustri lucidi extract on bone turnover and calcium balance in ovariectomized rats. Biol Pharm Bull 29:291–296

    Article  PubMed  Google Scholar 

  6. Zhang Y, Dong XL, Leung PC, Che CT, Wong MS (2008) Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats. Menopause 15:558–565

    Article  PubMed  Google Scholar 

  7. Zhang Y, Leung PC, Che CT, Chow HK, Wu CF, Wong MS (2008) Improvement of bone properties and enhancement of mineralization by ethanol extract of Fructus ligustri lucidi. Br J Nutr 99:494–502

    CAS  PubMed  Google Scholar 

  8. Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 194:S3–S11

    Article  CAS  PubMed  Google Scholar 

  9. Pitkin RM (1985) Calcium metabolism in pregnancy and the perinatal period: a review. Am J Obstet Gynecol 151:99–109

    Article  CAS  PubMed  Google Scholar 

  10. Emkey RD, Emkey GR (2012) Calcium metabolism and correcting calcium deficiencies. Endocrinol Metab Clin N Am 41:527–556

    Article  Google Scholar 

  11. Gennari C (2001) Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutr 4:547–559

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Zhu J, DeLuca H (2012) Where is the vitamin D receptor. Arch Biochem Biophys 523:123–133

    Article  CAS  PubMed  Google Scholar 

  13. Song Y, Peng X, Porta A, Takanaga H, Peng JB, Hediger MA, Fleet JC, Christakos S (2003) Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology 144:3885–3894

    Article  CAS  PubMed  Google Scholar 

  14. Bouillon R, Van Cromphaut S, Carmeliet G (2003) Intestinal calcium absorption: molecular vitamin D mediated mechanisms. J Cell Biochem 88:332–339

    Article  CAS  PubMed  Google Scholar 

  15. Christakos S (2012) Recent advances in our understanding of 1,25-dihydroxyvitamin D(3) regulation of intestinal calcium absorption. Arch Biochem Biophys 523:73–76

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Clark J, Gebhart G, Gonder J, Keeling M, Kohn D (1997) The 1996 guide for the care and use of laboratory animals. ILAR J 38:41–48

    Article  PubMed  Google Scholar 

  17. Radonic A, Thulke S, Mackay IM, Landt O, Siegert W, Nitsche A (2004) Guideline to reference gene selection for quantitative real-time PCR. Biochem Biophys Res Commun 313:856–862

    Article  CAS  PubMed  Google Scholar 

  18. Wada S, Kamiya S (2006) Bone and bone related biochemical examinations. Bone and collagen related metabolites. Osteocalcin (OC). Clin Calcium 16:1017–1021

    CAS  PubMed  Google Scholar 

  19. Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 228:1149–1153

    Article  CAS  PubMed  Google Scholar 

  20. Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD (2000) Serum type I collagen breakdown product (serum CTX) predicts hip fracture risk in elderly women: the EPIDOS study. Bone 27:283–286

    Article  CAS  PubMed  Google Scholar 

  21. Rosen HN, Moses AC, Garber J, Iloputaife ID, Ross DS, Lee SL, Greenspan SL (2000) Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 66:100–103

    Article  CAS  PubMed  Google Scholar 

  22. Fong L, Muhlhausler BS, Gibson RA, Xian CJ (2012) Perinatal maternal dietary supplementation of omega3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring. Endocrinology 153:2455–2465

    Article  CAS  PubMed  Google Scholar 

  23. Christakos S, Dhawan P, Porta A, Mady LJ, Seth T (2011) Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol 347:25–29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Fleet JC, Schoch RD (2010) Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D and other factors. Crit Rev Clin Lab Sci 47:181–195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Miller WL, Portale AA (2000) Vitamin D 1 alpha-hydroxylase. Trends Endocrinol Metab 11:315–319

    Article  CAS  PubMed  Google Scholar 

  26. Bikle DD (2012) Vitamin D and bone. Curr Osteoporos Rep 10:151–159

    Article  PubMed Central  PubMed  Google Scholar 

  27. Dong XL, Zhang Y, Favus MJ, Che CT, Wong MS (2010) Ethanol extract of Fructus ligustri lucidi increases circulating 1,25-dihydroxyvitamin D3 by inducing renal 25-hydroxyvitamin D-1alpha hydroxylase activity. Menopause 17:1174–1181

    Article  PubMed  Google Scholar 

  28. Wu S, Ren S, Nguyen L, Adams JS, Hewison M (2007) Splice variants of the CYP27b1 gene and the regulation of 1,25-dihydroxyvitamin D3 production. Endocrinology 148:3410–3418

    Article  CAS  PubMed  Google Scholar 

  29. Shi L, Ma Y, Cai Z (1998) Quantitative determination of salidroside and specnuezhenide in the fruits of Ligustrum lucidum Ait. by high performance liquid chromatography. Biomed Chromatogr 12:27–30

    Article  CAS  PubMed  Google Scholar 

  30. Lin HM, Yen FL, Ng LT, Lin CC (2007) Protective effects of Ligustrum lucidum fruit extract on acute butylated hydroxytoluene-induced oxidative stress in rats. J Ethnopharmacol 111:129–136

    Article  CAS  PubMed  Google Scholar 

  31. Xia EQ, Yu YY, Xu XR, Deng GF, Guo YJ, Li HB (2012) Ultrasound-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait. Ultrason Sonochem 19:772–776

    Article  CAS  PubMed  Google Scholar 

  32. Liu J (1995) Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49:57–68

    Article  CAS  PubMed  Google Scholar 

  33. Lee SU, Park SJ, Kwak HB, Oh J, Min YK, Kim SH (2008) Anabolic activity of ursolic acid in bone: stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo. Pharmacol Res 58:290–296

    Article  CAS  PubMed  Google Scholar 

  34. Li JX, Hareyama T, Tezuka Y, Zhang Y, Miyahara T, Kadota S (2005) Five new oleanolic acid glycosides from Achyranthes bidentata with inhibitory activity on osteoclast formation. Planta Med 71:673–679

    Article  CAS  PubMed  Google Scholar 

  35. Sultana N (2011) Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product. J Enzyme Inhib Med Chem 26:616–642

    Article  CAS  PubMed  Google Scholar 

  36. Sultana N, Ata A (2008) Oleanolic acid and related derivatives as medicinally important compounds. J Enzym Inhib Med Chem 23:739–756

    Article  CAS  Google Scholar 

  37. Murakami S, Takashima H, Sato-Watanabe M, Chonan S, Yamamoto K, Saitoh M, Saito S, Yoshimura H, Sugawara K, Yang J, Gao N, Zhang X (2004) Ursolic acid, an antagonist for transforming growth factor (TGF)-beta1. FEBS Lett 566:55–59

    Article  CAS  PubMed  Google Scholar 

  38. Yoshimura H, Sugawara K, Saito M, Saito S, Murakami S, Miyata N, Kawashima A, Morimoto S, Gao N, Zhang X, Yang J (2003) In vitro TGF-beta1 antagonistic activity of ursolic and oleanolic acids isolated from Clerodendranthus spicatus. Planta Med 69:673–675

    Article  CAS  PubMed  Google Scholar 

  39. Roberts AB (1998) Molecular and cell biology of TGF-beta. Miner Electrolyte Metab 24:111–119

    Article  CAS  PubMed  Google Scholar 

  40. Adams JS, Hewison M (2012) Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 523:95–102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435

    Article  CAS  PubMed  Google Scholar 

  42. Quarles LD (2012) Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol 8:276–286

    Article  CAS  PubMed  Google Scholar 

  43. Dangpei L (2010) Effects of FGF-23 overexpression on SOD and GSH2PX activity and MDA contents in mouse renal, hepatic and hippocampal tissues. J Southeast Univ (Med Sci Ed) 29:123–126

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, 100191, China

    Xin Feng, Ying Lyu, Zhenghao Wu, Yuehui Fang, Hao Xu & Yajun Xu

  2. Nestlé Research Centre, Beijing, 100095, China

    Pengling Zhao & Haotian Feng

  3. Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, China

    Yajun Xu

Authors
  1. Xin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Lyu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenghao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuehui Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hao Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pengling Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yajun Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haotian Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yajun Xu or Haotian Feng.

Additional information

Xin Feng and Ying Lyu have contributed equally to this article.

Dr. Xin Feng, Dr. Ying Lyu, Dr. Zhenghao Wu, Dr. Yuehui Fang, Dr. Hao Xu, Dr. Pengling Zhao, Dr. Yajun Xu and Dr. Haotian Feng has nothing to disclose.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, X., Lyu, Y., Wu, Z. et al. Fructus ligustri lucidi Ethanol Extract Improves Bone Mineral Density and Properties Through Modulating Calcium Absorption-Related Gene Expression in Kidney and Duodenum of Growing Rats. Calcif Tissue Int 94, 433–441 (2014). https://doi.org/10.1007/s00223-013-9825-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-013-9825-4

Keywords

Search

Navigation