Download PDF
Planta Med 2017; 83(16): 1264-1273
DOI: 10.1055/s-0043-108761
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats

Guanghua Chen   *
1   Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
,
Xinle Zhang   *
2   Department of Pharmacology, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong, China
,
Han Lin   *
3   Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guian, Guizhou, China
,
Guizhi Huang   *
1   Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
,
Yahui Chen
2   Department of Pharmacology, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong, China
,
Liao Cui
2   Department of Pharmacology, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong, China
4   Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong, China
› Author Affiliations
Further Information

Publication History

received 07 January 2017
revised 23 March 2017

accepted 02 April 2017

Publication Date:
20 April 2017 (online)

    Permissions and Reprints

Abstract

Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards, all animals underwent a surgical procedure to induce bone defects at the right proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or calcitriol treatment was continued to the endpoint. At the experimental endpoint, compared to the model group, 25 mg/kg tanshinol could significantly reverse glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing mechanical bone strength, causing a significant 11 % increase in trabecular number, and reducing trabecular separation by 28 %. In addition, tanshinol improved the bone microarchitecture and prevented glucocorticoid-induced bone loss by promoting bone formation and inhibiting bone resorption. Moreover, results of bone defect repair and muscle weight measurements revealed that tanshinol accelerated the bone fracture healing process and attenuated muscle atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold increases in vascular endothelial growth factor mRNA expression in calluses from the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels from glucocorticoid-induced elevation. These findings demonstrate the potential benefits of tanshinol against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy, which warrants further investigation in future studies.

Key words

glucocorticoid - osteoporosis - fracture - myopathy - tanshinol - Salvia miltiorrhiza - Lamiaceae - bone histomorphometry

* These authors contributed equally to this work.


Supporting Information

    The experimental scheme used in this study and results of static and/or dynamic histomorphometric analyses of the effects of Tanshinol on bone histomorphology of PTM, TX, and LV5 are available as Supporting Information.

  • Supporting Information
 

  • References

  • 1 Müller R, Kampschulte M, Khassawna TE, Schlewitz G, Hürter B, Böcker W, Bobeth M, Langheinrich AC, Heiss C, Deutsch A, Cuniberti G. Change of mechanical vertebrae properties due to progressive osteoporosis: combined biomechanical and finite-element analysis within a rat model. Med Biol Eng Comput 2014; 52: 405-414
    CrossrefPubMedGoogle Scholar
  • 2 Siu WS, Ko CH, Lam KW, Wat E, Shum WT, Lau CB, Ko KM, Hung LK, Lau DT, Leung PC. Evaluation of a topical herbal agent for the promotion of bone healing. Evid Based Complement Alternat Med 2015; 2015: 905270
    PubMedGoogle Scholar
  • 3 Bindl R, Oheim R, Pogoda P, Beil FT, Gruchenberg K, Reitmaier S, Wehner T, Calcia E, Radermacher P, Claes L, Amling M, Ignatius A. Metaphyseal fracture healing in a sheep model of low turnover osteoporosis induced by hypothalamic-pituitary disconnection (HPD). J Orthop Res 2013; 31: 1851-1857
    CrossrefPubMedGoogle Scholar
  • 4 Lim SY, Bolster MB. Current approaches to osteoporosis treatment. Curr Opin Rheumatol 2015; 27: 216-224
    CrossrefPubMedGoogle Scholar
  • 5 Briot K, Roux C. Glucocorticoid-induced osteoporosis. RMD Open 2015; 1: e000014
    CrossrefPubMedGoogle Scholar
  • 6 Scillitani A, Mazziotti G, Di Somma C, Moretti S, Stigliano A, Pivonello R, Giustina A, Colao A, Group ABC. Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?. Osteoporos Int 2014; 25: 441-446
    PubMedGoogle Scholar
  • 7 Tu J, Henneicke H, Zhang Y, Stoner S, Cheng TL, Schindeler A, Chen D, Tuckermann J, Cooper MS, Seibel MJ, Zhou H. Disruption of glucocorticoid signaling in chondrocytes delays metaphyseal fracture healing but does not affect normal cartilage and bone development. Bone 2014; 69: 12-22
    CrossrefPubMedGoogle Scholar
  • 8 Peppone LJ, Hebl S, Purnell JQ, Reid ME, Rosier RN, Mustian KM, Palesh OG, Huston AJ, Ling MN, Morrow GR. The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review. Osteoporos Int 2010; 21: 1133-1149
    CrossrefPubMedGoogle Scholar
  • 9 Kenanidis E, Potoupnis ME, Kakoulidis P, Leonidou A, Sakellariou GT, Sayegh FE, Tsiridis E. Management of glucocorticoid-induced osteoporosis: clinical data in relation to disease demographics, bone mineral density and fracture risk. Expert Opin Drug Saf 2015; 14: 1035-1053
    CrossrefPubMedGoogle Scholar
  • 10 Rossini M, Orsolini G, Viapiana O, Adami S, Gatti D. Bisphosphonates in the treatment of glucocorticoid-induced osteoporosis: pros. Endocrine 2015; 49: 620-627
    CrossrefPubMedGoogle Scholar
  • 11 Doga M, Mazziotti G, Bonadonna S, Patelli I, Bilezikian JP, Canalis E, Giustina A. Prevention and treatment of glucocorticoid-induced osteoporosis. J Endocrinol Invest 2008; 31: 53-58
    PubMedGoogle Scholar
  • 12 Li C, Li Q, Liu R, Niu Y, Pan Y, Zhai Y, Mei Q. Medicinal herbs in the prevention and treatment of osteoporosis. Am J Chin Med 2014; 42: 1-22
    CrossrefPubMedGoogle Scholar
  • 13 Cui Y, Bhandary B, Marahatta A, Lee GH, Li B, Kim DS, Chae SW, Kim HR, Chae HJ. Characterization of Salvia miltiorrhiza ethanol extract as an anti-osteoporotic agent. BMC Complement Altern Med 2011; 11: 120
    CrossrefPubMedGoogle Scholar
  • 14 Cui L, Li T, Liu Y, Zhou L, Li P, Xu B, Huang L, Chen Y, Liu Y, Tian X, Jee WS, Wu T. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis. PLoS One 2012; 7: e34647
    CrossrefPubMedGoogle Scholar
  • 15 Cui L, Liu YY, Wu T, Ai CM, Chen HQ. Osteogenic effects of D+beta-3,4-dihydroxyphenyl lactic acid (salvianic acid A, SAA) on osteoblasts and bone marrow stromal cells of intact and prednisone-treated rats. Acta Pharmacol Sin 2009; 30: 321-332
    PubMedGoogle Scholar
  • 16 Yang Y, Su Y, Wang D, Chen Y, Wu T, Li G, Sun X, Cui L. Tanshinol attenuates the deleterious effects of oxidative stress on osteoblastic differentiation via Wnt/FoxO3a signaling. Oxid Med Cell Longev 2013; 2013: 351895
    PubMedGoogle Scholar
  • 17 Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000; 11: 192-202
    CrossrefPubMedGoogle Scholar
  • 18 Lewiecki EM, Lane NE. Common mistakes in the clinical use of bone mineral density testing. Nat Clin Pract Rheumatol 2008; 4: 667-674
    CrossrefPubMedGoogle Scholar
  • 19 Weng MY, Lane NE. Medication-induced osteoporosis. Curr Osteoporos Rep 2007; 5: 139-145
    CrossrefPubMedGoogle Scholar
  • 20 Leib ES, Winzenrieth R. Bone status in glucocorticoid-treated men and women. Osteoporos Int 2016; 27: 39-48
    CrossrefPubMedGoogle Scholar
  • 21 Weinstein RS. Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin North Am 2012; 41: 595-611
    CrossrefPubMedGoogle Scholar
  • 22 Delany AM, Pereira RM, Pereira RC, Canalis E. The cellular and molecular basis of glucocorticoid actions in bone. Front Horm Res 2002; 30: 2-12
    PubMedGoogle Scholar
  • 23 Oktas B, Orhan Z, Erbil B, Degirmenci E, Ustundag N. Effect of extracorporeal shock wave therapy on fracture healing in rat femural fractures with intact and excised periosteum. Eklem Hastalik Cerrahisi 2014; 25: 158-162
    CrossrefPubMedGoogle Scholar
  • 24 Tajima S, Tobita M, Orbay H, Hyakusoku H, Mizuno H. Direct and indirect effects of a combination of adipose-derived stem cells and platelet-rich plasma on bone regeneration. Tissue Eng Part A 2015; 21: 895-905
    CrossrefPubMedGoogle Scholar
  • 25 Krishnan L, Priddy LB, Esancy C, Li MT, Stevens HY, Jiang X, Tran L, Rowe DW, Guldberg RE. Hydrogel-based delivery of rhBMP-2 improves healing of large bone defects compared with autograft. Clin Orthop Relat Res 2015; 473: 2885-2897
    CrossrefPubMedGoogle Scholar
  • 26 Weigand A, Beier JP, Hess A, Gerber T, Arkudas A, Horch RE, Boos AM. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Eng Part A 2015; 21: 1680-1694
    CrossrefPubMedGoogle Scholar
  • 27 Mazziotti G, Giustina A, Canalis E, Bilezikian JP. Glucocorticoid-induced osteoporosis: clinical and therapeutic aspects. Arq Bras Endocrinol Metabol 2007; 51: 1404-1412
    CrossrefPubMedGoogle Scholar
  • 28 Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag 2009; 5: 305-310
    PubMedGoogle Scholar
  • 29 Zelzer E, McLean W, Ng YS, Fukai N, Reginato AM, Lovejoy S, DʼAmore PA, Olsen BR. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development 2002; 129: 1893-1904
    PubMedGoogle Scholar
  • 30 Street J, Bao M, deGuzman L, Bunting S, Peale jr. FV, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 2002; 99: 9656-9661
    CrossrefPubMedGoogle Scholar
  • 31 Peng H, Wright V, Usas A, Gearhart B, Shen HC, Cummins J, Huard J. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 2002; 110: 751-759
    CrossrefPubMedGoogle Scholar
  • 32 Shi CG, Yang YS, Li H, Zhang Y, Wang N, Wang SM, Wang JD, Zhang SC. Tanshinol protects hippocampus and attenuates vascular dementia development. J Asian Nat Prod Res 2014; 16: 667-676
    CrossrefPubMedGoogle Scholar
  • 33 Schakman O, Kalista S, Barbe C, Loumaye A, Thissen JP. Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol 2013; 45: 2163-2172
    CrossrefPubMedGoogle Scholar
  • 34 SantʼAnna EF, Leven RM, Virdi AS, Sumner DR. Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res 2005; 23: 646-652
    CrossrefPubMedGoogle Scholar
  • 35 Zhu LJ, Altmann SW. mRNA and 18S-RNA coapplication-reverse transcription for quantitative gene expression analysis. Anal Biochem 2005; 345: 102-109
    CrossrefPubMedGoogle Scholar