Skip to main content

Advertisement

SpringerLink
Log in

Prevention of disuse osteoporosis in rats by Cordyceps sinensis extract

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Cordyceps sinensis has been known as a traditional medicine in China, and C. sinensis plus strontium could prevent osteoporosis in ovariectomized rats. The present study shows that daily oral administration of C. sinensis at higher doses in adult hind limb suspension rats can prevent disuse-induced bone loss and deterioration of trabecular microarchitecture.

Introduction

Cordyceps sinensis induces estradiol production and prevents osteoporosis in ovariectomized rats. This study was to examine whether C. sinensis can prevent disuse-induced osteoporosis.

Methods

Rats were randomly divided into six groups, and five groups were treated with hind limb suspension (HLS). One HLS group received alendronate (2.0 mg/kg/day) orally, and to the three other HLS groups to each group, a different amount of C. sinensis (100, 300, and 500 mg/kg/day) was orally administered for 8 weeks before and after HLS. The remaining HLS group was set as a control without treatment. Each group consisted of 10 males and females. The body weights, biochemical parameters in serum and urine, bone mineral density (BMD), bone mineral content (BMC), mechanical testing, and bone microarchitecture were examined.

Results

Treatments with higher C. sinensis dosage (300 and 500 mg/kg/day) or alendronate had a positive effect on body weights, mechanical strength, BMD, and BMC compared to the other HLS groups. C. sinensis decreased markers of bone turnover dose dependently and increased the osteocalcin levels in HLS rats. The result of micro-CT analysis from the L4 vertebra showed that C. sinensis (500 mg/kg) significantly prevented the reduction of the bone volume fraction, connectivity density, trabeculae number, and thickness as well as improved the trabeculae separation and structure model index in HLS rats.

Conclusions

The present study demonstrates that administration of C. sinensis at higher doses over an 8-week period can prevent the disuse osteoporosis in rats. It implies that C. sinensis might be an alternative therapy for prevention of disuse-induced osteoporosis also in humans.

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. Berecki-Gisolf J, Spallek M, Hockey R, Dobson A (2010) Height loss in elderly women is preceded by osteoporosis and is associated with digestive problems and urinary incontinence. Osteoporos Int 21:479–485

    Article  PubMed  CAS  Google Scholar 

  2. Oinuma T, Sakuma M, Endo N (2010) Secular change of the incidence of four fracture types associated with senile osteoporosis in Sado, Japan: the results of a 3-year survey. J Bone Miner Metab 28:55–59

    Article  PubMed  Google Scholar 

  3. Li CY, Price C, Delisser K, Nasser P, Laudier D, Clement M, Jepsen KJ, Schaffler MB (2005) Long-term disuse osteoporosis seems less sensitive to bisphosphonate treatment than other osteoporosis. J Bone Miner Res 20:117–124

    Article  PubMed  CAS  Google Scholar 

  4. Garber MA, McDowell DL, Hutton WC (2000) Bone loss during simulated weightlessness: a biomechanical and mineralization study in the rat model. Aviat Space Environ Med 71:586–592

    PubMed  CAS  Google Scholar 

  5. van der Meulen MC, Morey-Holton ER, Carter DR (1995) Hindlimb suspension diminishes femoral cross-sectional growth in the rat. J Orthop Res 13:700–707

    Article  PubMed  Google Scholar 

  6. Caillot-Augusseau A, Vico L, Heer M, Voroviev D, Souberbielle JC, Zitterman A, Alexandre C, Lafage-Proust MH (2000) Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts. Clin Chem 46:1136–1143

    PubMed  CAS  Google Scholar 

  7. Kiratli BJ, Smith AE, Nauenberg T, Kallfelz CF, Perkash I (2000) Bone mineral and geometric changes through the femur with immobilization due to spinal cord injury. J Rehabil Res Dev 37:225–233

    PubMed  CAS  Google Scholar 

  8. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19:1006–1012

    Article  PubMed  Google Scholar 

  9. Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D (2004) Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 97:119–129

    Article  PubMed  CAS  Google Scholar 

  10. Yang Li C, Majeska RJ, Laudier DM, Mann R, Schaffler MB (2005) High-dose risedronate treatment partially preserves cancellous bone mass and microarchitecture during long-term disuse. Bone 37:287–295

    Article  PubMed  Google Scholar 

  11. Zhu JS, Halpern GM, Jones K (1998) The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I. J Altern Complement Med 4:289–303

    Article  PubMed  CAS  Google Scholar 

  12. Zhu JS, Halpern GM, Jones K (1998) The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II. J Altern Complement Med 4:429–457

    Article  PubMed  CAS  Google Scholar 

  13. Deitch AD, Sawicki SG (1979) Effects of cordycepin on microtubules of cultured mammalian cells. Exp Cell Res 118:1–13

    Article  PubMed  CAS  Google Scholar 

  14. Lee HS, Kim MK, Kim YK, Jung EY, Park CS, Woo MJ, Lee SH, Kim JS, Suh HJ (2011) Stimulation of osteoblastic differentiation and mineralization in MC3T3-E1 cells by antler and fermented antler using Cordyceps militaris. J Ethnopharmacol 133:710–717

    Article  PubMed  Google Scholar 

  15. Huang LF, Liang YZ, Guo FQ, Zhou ZF, Cheng BM (2003) Simultaneous separation and determination of active components in Cordyceps sinensis and Cordyceps militarris by LC/ESI-MS. J Pharm Biomed Anal 33:1155–1162

    Article  PubMed  CAS  Google Scholar 

  16. Shin S, Lee S, Kwon J, Moon S, Lee S, Lee CK, Cho K, Ha NJ, Kim K (2009) Cordycepin suppresses expression of diabetes regulating genes by inhibition of lipopolysaccharide-induced inflammation in macrophages. Immune Netw 9:98–105

    Article  PubMed  Google Scholar 

  17. Jeong JW, Jin CY, Kim GY et al (2010) Anti-inflammatory effects of cordycepin via suppression of inflammatory mediators in BV2 microglial cells. Int Immunopharmacol 10:1580–1586

    Article  PubMed  CAS  Google Scholar 

  18. Wang Y, Wang M, Ling Y, Fan W, Yin H (2009) Structural determination and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps sinensis. Am J Chin Med 37:977–989

    Article  PubMed  Google Scholar 

  19. Huang BM, Hsiao KY, Chuang PC, Wu MH, Pan HA, Tsai SJ (2004) Upregulation of steroidogenic enzymes and ovarian 17beta-estradiol in human granulosa-lutein cells by Cordyceps sinensis mycelium. Biol Reprod 70:1358–1364

    Article  PubMed  CAS  Google Scholar 

  20. Qi W, Yan YB, Wang PJ, Lei W (2010) The co-effect of Cordyceps sinensis and strontium on osteoporosis in ovariectomized osteopenic rats. Biol Trace Elem Res 141(1–3):216–223

    PubMed  Google Scholar 

  21. Qi W, Wang PJ, Guo WJ, Yan YB, Zhang Y, Lei W (2010) The mechanism of Cordyceps sinensis and strontium in prevention of osteoporosis in rats. Biol Trace Elem Res 143(1):302–309

    Article  PubMed  Google Scholar 

  22. Chang Y, Jeng KC, Huang KF, Lee YC, Hou CW, Chen KH, Cheng FY, Liao JW, Chen YS (2008) Effect of Cordyceps militaris supplementation on sperm production, sperm motility and hormones in Sprague–Dawley rats. Am J Chin Med 36:849–859

    Article  PubMed  CAS  Google Scholar 

  23. Morey-Holton ER, Globus RK (2002) Hindlimb unloading rodent model: technical aspects. J Appl Physiol 92:1367–1377

    Article  PubMed  Google Scholar 

  24. Liu Z, Li P, Zhao D, Tang H, Guo J (2010) Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Behav Brain Funct 6:61

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. FDA (2002) Guidance for industry and reviews: estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers [S]. 12

  27. Huang JH HX, Chen ZY et al (2004) Dose conversion among different animals and healthy volunteers in pharmacological study. Chin J Clin Pharmacol Ther 9:1069–1072

    Google Scholar 

  28. Changrani NR, Chonkar A, Adeghate E, Singh J (2006) Effects of streptozotocin-induced type 1 diabetes mellitus on total protein concentrations and cation contents in the isolated pancreas, parotid, submandibular, and lacrimal glands of rats. Ann N Y Acad Sci 1084:503–519

    Article  PubMed  CAS  Google Scholar 

  29. Ma Z, Fu Q (2010) Comparison of the therapeutic effects of yeast-incorporated gallium with those of inorganic gallium on ovariectomized osteopenic rats. Biol Trace Elem Res 134:280–287

    Article  PubMed  CAS  Google Scholar 

  30. Zhang G, Qin L, Hung WY, Shi YY, Leung PC, Yeung HY, Leung KS (2006) Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption. Bone 38:818–825

    Article  PubMed  CAS  Google Scholar 

  31. Havill LM, Hale LG, Newman DE, Witte SM, Mahaney MC (2006) Bone ALP and OC reference standards in adult baboons (Papio hamadryas) by sex and age. J Med Primatol 35:97–105

    Article  PubMed  CAS  Google Scholar 

  32. Ross PD, Kress BC, Parson RE, Wasnich RD, Armour KA, Mizrahi IA (2000) Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study. Osteoporos Int 11:76–82

    Article  PubMed  CAS  Google Scholar 

  33. Halleen JM, Ylipahkala H, Alatalo SL, Janckila AJ, Heikkinen JE, Suominen H, Cheng S, Vaananen HK (2002) Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density. Calcif Tissue Int 71:20–25

    Article  PubMed  CAS  Google Scholar 

  34. Qin YJ, Zhang ZL, Zhang H, Hu WW, Liu YJ, Hu YQ, Li M, Gu JM, He JW (2008) Age-related changes of serum tartrate-resistant acid phosphatase 5b and the relationship with bone mineral density in Chinese women. Acta Pharmacol Sin 29:1493–1498

    Article  PubMed  CAS  Google Scholar 

  35. Bessey OA, Lowry OH, Brock MJ (1946) A method for the rapid determination of alkaline phosphates with five cubic millimeters of serum. J Biol Chem 164:321–329

    PubMed  CAS  Google Scholar 

  36. Kanbur NO, Derman O, Sen TA, Kinik E (2002) Osteocalcin. A biochemical marker of bone turnover during puberty. Int J Adolesc Med Health 14:235–244

    Article  PubMed  Google Scholar 

  37. Burgeson RE (1988) New collagens, new concepts. Annu Rev Cell Biol 4:551–577

    Article  PubMed  CAS  Google Scholar 

  38. Guerrero R, Diaz Martin MA, Diaz Diego EM, Disla T, Rapado A, de la Piedra C (1996) New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis. Osteoporos Int 6:297–302

    Article  PubMed  CAS  Google Scholar 

  39. Madyastha PR, Yang S, Ries WL, Key LL Jr (2000) IFN-gamma enhances osteoclast generation in cultures of peripheral blood from osteopetrotic patients and normalizes superoxide production. J Interferon Cytokine Res 20:645–652

    Article  PubMed  CAS  Google Scholar 

  40. Mundy GR (1993) Role of cytokines in bone resorption. J Cell Biochem 53:296–300

    Article  PubMed  CAS  Google Scholar 

  41. Petricevich VL, Lebrun I (2005) Immunomodulatory effects of the Tityus serrulatus venom on murine macrophage functions in vitro. Mediators Inflamm 2005:39–49

    Article  PubMed  Google Scholar 

  42. Bagi CM, Miller SC (1994) Comparison of osteopenic changes in cancellous bone induced by ovariectomy and/or immobilization in adult rats. Anat Rec 239:243–254

    Article  PubMed  CAS  Google Scholar 

  43. Turner RT, Riggs BL, Spelsberg TC (1994) Skeletal effects of estrogen. Endocr Rev 15:275–300

    PubMed  CAS  Google Scholar 

  44. Dang ZC, van Bezooijen RL, Karperien M, Papapoulos SE, Lowik CW (2002) Exposure of KS483 cells to estrogen enhances osteogenesis and inhibits adipogenesis. J Bone Miner Res 17:394–405

    Article  PubMed  CAS  Google Scholar 

  45. Laib A, Kumer JL, Majumdar S, Lane NE (2001) The temporal changes of trabecular architecture in ovariectomized rats assessed by MicroCT. Osteoporos Int 12:936–941

    Article  PubMed  CAS  Google Scholar 

  46. Tsunoo A, Takemoto NN, Tsuboi H, Kamijo MA et al. (1995) Cordyceps sinensis: its diverse effects on mammals in vitro and in vivo. In: New initiatives in mycological research. Proceedings of the Third International Symposium of the Mycological Society of Japan, pp. 1–10

  47. Yao W, Tian XY, Chen J, Setterberg RB, Lundy MW, Chmielzwski P, Froman CA, Jee WS (2007) Rolipram, a phosphodiesterase 4 inhibitor, prevented cancellous and cortical bone loss by inhibiting endosteal bone resorption and maintaining the elevated periosteal bone formation in adult ovariectomized rats. J Musculoskelet Neuronal Interact 7:119–130

    PubMed  CAS  Google Scholar 

  48. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11(Suppl 6):S2–S17

    Article  PubMed  Google Scholar 

  49. Gaumet N, Seibel MJ, Coxam V, Davicco MJ, Lebecque P, Barlet JP (1997) Influence of ovariectomy and estradiol treatment on calcium homeostasis during aging in rats. Arch Physiol Biochem 105:435–444

    Article  PubMed  CAS  Google Scholar 

  50. Akhter MP, Alvarez GK, Cullen DM, Recker RR (2010) Disuse-related decline in trabecular bone structure. Biomech Model Mechanobiol 10(3):423–429

    Article  PubMed  Google Scholar 

  51. Bouxsein ML (2003) Mechanisms of osteoporosis therapy: a bone strength perspective. Clin Cornerstone Suppl 2:S13–S21

    Article  PubMed  Google Scholar 

  52. Li SP, Su ZR, Dong TT, Tsim KW (2002) The fruiting body and its caterpillar host of Cordyceps sinensis show close resemblance in main constituents and anti-oxidation activity. Phytomedicine 9:319–324

    Article  PubMed  CAS  Google Scholar 

  53. Won SY, Park EH (2005) Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharmacol 96:555–561

    Article  PubMed  Google Scholar 

  54. Hefferan TE, Evans GL, Lotinun S, Zhang M, Morey-Holton E, Turner RT (2003) Effect of gender on bone turnover in adult rats during simulated weightlessness. J Appl Physiol 95:1775–1780

    PubMed  CAS  Google Scholar 

  55. Lindsay R (1993) Pathogenesis of postmenopausal osteoporosis. Baillieres Clin Rheumatol 7:499–513

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

Grant support from The National High Technology Research and Development Program of China (863 Program) (2007AA02Z468) was received in support of this work. No benefits in any form have been or will be received from a commercial party directly or indirectly by the authors of this manuscript.

Ethics statement

All the procedures involving use of animals were conducted according to the ethics guidelines established by the Fourth Military Medical University.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, No 15, Changle West Road, Xi’an, 710032, China

    W. Qi, Y.-B. Yan, W. Lei, Z.-X. Wu, Y. Zhang, D. Liu, L. Shi, P.-C. Cao & N. Liu

  2. Department of Surgery, 520th Hospital of People’s Liberation Army, Mianyang, 621000, China

    W. Qi

Authors
  1. W. Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y.-B. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Z.-X. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P.-C. Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. Lei.

Additional information

Wei Qi and Ya-bo Yan contributed equally to this work as co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qi, W., Yan, YB., Lei, W. et al. Prevention of disuse osteoporosis in rats by Cordyceps sinensis extract. Osteoporos Int 23, 2347–2357 (2012). https://doi.org/10.1007/s00198-011-1842-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-011-1842-4

Keywords

Search

Navigation