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The effect of icariin on bone metabolism and its potential clinical application

Abstract

Osteoporosis is a bone disease characterized by reduced bone mass, which leads to increased risk of bone fractures, and poses a significant risk to public health, especially in the elderly population. The traditional Chinese medicinal herb Epimedii has been utilized for centuries to treat bone fracture and bone loss. Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be the main bioactive component. This review provides a comprehensive survey of previous studies on icariin, including its structure and function, effect on bone metabolism, and potential for clinical application. These studies show that icariin promotes bone formation by stimulating osteogenic differentiation of BMSCs (bone marrow-derived mesenchymal stem cells), while inhibiting osteoclastogenic differentiation and the bone resorption activity of osteoclasts. Furthermore, icariin has been shown to be more potent than other flavonoid compounds in promoting osteogenic differentiation and maturation of osteoblasts. A 24-month randomized double-blind placebo-controlled clinical trial reported that icariin was effective in preventing postmenopausal osteoporosis with relatively low side effects. In conclusion, icariin may represent a class of flavonoids with bone-promoting activity, which could be used as potential treatment of postmenopausal osteoporosis.

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Abbreviations

AAPH:

2,2′-azobis(2-amidinopropane) dihydrochloride

ALP:

alkaline phosphatase

ABCB1:

ATP-binding cassette subfamily B member 1

BMP:

bone morphogenetic protein

BMSC:

bone marrow-derived mesenchymal stem cells

Cebpb:

CCAAT/enhancer-binding protein β

CTX:

carboxy-terminal collagen cross-links

Col-1:

type I collagen

ERs:

estrogen receptors

ERK:

extracellular signal-regulated kinase

GSK-3β:

glycogen synthase kinase-3

Id-1:

inhibitor of DNA-binding 1

JNK:

c-Jun N terminal kinase

LPS:

lipopolysaccharide

MMP:

mitochondrial membrane potential

NO:

nitric oxide

OC:

osteocalcin

ONFH:

osteonecrosis of femoral head

OPG:

osteoprotegerin

·O2−:

superoxide anion

P-gp:

P-glycoprotein

ROS:

reactive oxygen species

Pparg:

peroxisome proliferator-activated receptor γ

Runx2:

runt-related transcription factor 2

RANKL:

receptor activator of nuclear factor kappa-B ligand

TRAP:

tartrate-resistant acid phosphatase

References

  1. Nih Consensus Development Panel on Osteoporosis Prevention D, Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

  2. Alexander IM (2009) Pharmacotherapeutic management of osteoprosis and osteopenia. Nurse Pract 34:30–40

    Article  PubMed  Google Scholar 

  3. de Bakker CM, Tseng WJ, Li Y, Zhao H, Liu XS (2017) Clinical evaluation of bone strength and fracture risk. Curr Osteoporos Rep 15:32–42

    Article  PubMed  Google Scholar 

  4. Anonymous (2010) Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause (New York, NY) 17:25–54 quiz 55–26

    Article  Google Scholar 

  5. Bone H (2012) Future directions in osteoporosis therapeutics. Endocrinol Metab Clin N Am 41:655–661

    Article  Google Scholar 

  6. Papapetrou PD (2009) Bisphosphonate-associated adverse events. Hormones 8:96–110

    Article  PubMed  Google Scholar 

  7. Chesnut CH, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, Leboff M, Maricic M, Miller P (2000) A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 109:267

    CAS  Article  PubMed  Google Scholar 

  8. Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M (2004) Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol 32:426

    CAS  Article  PubMed  Google Scholar 

  9. Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG (2016) Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 316:722

    CAS  Article  PubMed  Google Scholar 

  10. Jolette J, Attalla B, Varela A, Long GG, Mellal N, Trimm S, Smith SY, Ominsky MS, Hattersley G (2017) Comparing the incidence of bone tumors in rats chronically exposed to the selective PTH type 1 receptor agonist abaloparatide or PTH(1-34). Regul Toxicol Pharmacol 86:356–365

    CAS  Article  PubMed  Google Scholar 

  11. Zhang X, Liu T, Huang Y, Wismeijer D, Liu Y (2014) Icariin: does it have an osteoinductive potential for bone tissue engineering? Phytother Res 28:498–509

    CAS  Article  PubMed  Google Scholar 

  12. Qin L, Zhang G, Shi Y, Lee K, Leung P (2005) Prevention and treatment of osteoporosis with traditional herbal medicine. In: Deng HW, Liu YZ, Guo CY, Chen D (eds) Current topics in osteoporosis. World Scientific Publisher, Singapore, pp 513–531

  13. Ming LG, Chen KM, Xian CJ (2013) Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. J Cell Physiol 228:513–521

    CAS  Article  PubMed  Google Scholar 

  14. Fan J, Bi L, Wu T, Cao L, Wang D, Nan K, Chen J, Jin D, Jiang S, Pei G (2012) A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin. J Mater Sci Mater Med 23:399–407

    CAS  Article  PubMed  Google Scholar 

  15. Zhang X, Xu M, Song L, Wei Y, Lin Y, Liu W, Heng BC, Peng H, Wang Y, Deng X (2013) Effects of compatibility of deproteinized antler cancellous bone with various bioactive factors on their osteogenic potential. Biomaterials 34:9103–9114

    CAS  Article  PubMed  Google Scholar 

  16. Zhao J, Ohba S, Komiyama Y, Shinkai M, Chung UI, Nagamune T (2010) Icariin: a potential osteoinductive compound for bone tissue engineering. Tissue Eng A 16:233

    CAS  Article  Google Scholar 

  17. Chung BH, Kim JD, Kim CK, Kim JH, Won MH, Lee HS, Dong MS, Ha KS, Kwon YG, Kim YM (2008) Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. Biochem Biophys Res Commun 376:404–408

    CAS  Article  PubMed  Google Scholar 

  18. Seeman E (2009) Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr 19:219

    CAS  Article  PubMed  Google Scholar 

  19. Myneni VD, Mezey E (2016) Regulation of bone remodeling by vitamin K2. Oral Dis 23:1021–1028

  20. Sims NA, Gooi JH (2008) Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 19:444–451

    CAS  Article  PubMed  Google Scholar 

  21. Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455–498

    CAS  Article  PubMed  Google Scholar 

  22. Bar-Shavit Z (2007) The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem 102:1130–1139

    CAS  Article  PubMed  Google Scholar 

  23. Matsuo K, Irie N (2008) Osteoclast-osteoblast communication. Arch Biochem Biophys 473:201

    CAS  Article  PubMed  Google Scholar 

  24. Fennen M, Pap T, Dankbar B (2016) Smad-dependent mechanisms of inflammatory bone destruction. Arthritis Res Ther 18:279

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ginaldi L, De MM (2016) Osteoimmunology and beyond. Curr Med Chem 23:3754–3774

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S (1998) Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol 54:105–112

    CAS  Article  PubMed  Google Scholar 

  27. Manolagas SC, O’Brien CA, Almeida M (2013) The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 9:699–712

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Khalid AB, Krum SA (2016) Estrogen receptors alpha and beta in bone. Bone 87:130–135

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Xu F, Mcdonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121

    Article  Google Scholar 

  30. Abdallah BM, Al-Shammary A, Khattab HM, Aldahmash A, Kassem M (2016) Bone marrow stromal stem cells for bone repair: basic and translational aspects. Recent Advances in Stem Cells. Springer International Publishing, pp 213-232

  31. Zhao J, Ohba S, Shinkai M, Chung UI, Nagamune T (2008) Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner. Biochem Biophys Res Commun 369:444–448

    CAS  Article  PubMed  Google Scholar 

  32. Fan JJ, Cao LG, Wu T, Wang DX, Jin D, Jiang S, Zhang ZY, Bi L, Pei GX (2011) The dose-effect of icariin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cells. Molecules 16:10123–10133

  33. Nian H, Ma MH, Nian SS, Xu LL (2009) Antiosteoporotic activity of icariin in ovariectomized rats. Phytomedicine 16:320

    CAS  Article  PubMed  Google Scholar 

  34. Jee WS, Yao W (2001) Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 1:193

    CAS  PubMed  Google Scholar 

  35. Zhai YK, Guo XY, Ge BF, Zhen P, Ma XN, Zhou J, Ma HP, Xian CJ, Chen KM (2014) Icariin stimulates the osteogenic differentiation of rat bone marrow stromal cells via activating the PI3K–AKT–eNOS–NO–cGMP–PKG. Bone 66:189–198

    CAS  Article  PubMed  Google Scholar 

  36. Song L, Zhao J, Zhang X, Li H, Zhou Y (2013) Icariin induces osteoblast proliferation, differentiation and mineralization through estrogen receptor-mediated ERK and JNK signal activation. Eur J Pharmacol 714:15

    CAS  Article  PubMed  Google Scholar 

  37. Fu S, Yang L, Hong H, Zhang R (2016) Wnt/β-catenin signaling is involved in the icariin induced proliferation of bone marrow mesenchymal stem cells. J Tradit Chin Med 36:360–368

    Article  PubMed  Google Scholar 

  38. Wei Q, Zhang J, Hong G, Chen Z, Deng W, He W, Chen MH (2016) Icariin promotes osteogenic differentiation of rat bone marrow stromal cells by activating the ERα-Wnt/β-catenin signaling pathway. Biomed Pharmacother 84:931–939

    CAS  Article  PubMed  Google Scholar 

  39. Liang W, Lin M, Li X, Li C, Gao B, Gan H, Yang Z, Lin X, Liao L, Yang M (2012) Icariin promotes bone formation via the BMP-2/Smad4 signal transduction pathway in the hFOB 1.19 human osteoblastic cell line. Int J Mol Med 30:889–895

    CAS  Article  PubMed  Google Scholar 

  40. Cao H, Ke Y, Zhang Y, Zhang CJ, Qian W, Zhang GL (2012) Icariin stimulates MC3T3-E1 cell proliferation and differentiation through up-regulation of bone morphogenetic protein-2. Int J Mol Med 29:435

    CAS  PubMed  Google Scholar 

  41. Zhang ZB, Yang QT (2006) The testosterone mimetic properties of icariin. Asian J Androl 8:601

    CAS  Article  PubMed  Google Scholar 

  42. Liu J, Ye HY (2005) Determination of rat urinary metabolites of icariin in vivo and estrogenic activities of its metabolites on MCF-7 cells. Pharmazie 60:120–125

    PubMed  Google Scholar 

  43. Yang L, Lu D, Guo J, Meng X, Zhang G, Wang F (2013) Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19). J Ethnopharmacol 145:715–721

    CAS  Article  PubMed  Google Scholar 

  44. Sun Z, Yang S, Ye S, Zhang Y, Xu W, Zhang B, Liu X, Mo F, Hua W (2013) Aberrant CpG islands’ hypermethylation of ABCB1 in mesenchymal stem cells of patients with steroid-associated osteonecrosis. J Rheumatol 40:1913–1920

  45. Sun ZB, Wang JW, Xiao H, Zhang QS, Kan WS, Mo FB, Hu S, Ye SN (2015) Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study. Osteoporos Int 26:187

    CAS  Article  PubMed  Google Scholar 

  46. Zhao F, Tang YZ, Liu ZQ (2007) Protective effect of icariin on DNA against radical-induced oxidative damage. J Pharm Pharmacol 59:1729–1732

    CAS  Article  PubMed  Google Scholar 

  47. Chen KM, Ma HP, Ge BF, Liu XY, Ma LP, Bai MH, Wang Y (2007) Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats. Pharmazie 62:785–789

    CAS  PubMed  Google Scholar 

  48. Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME (2006) Playing with bone and fat. J Cell Biochem 98:251

    CAS  Article  PubMed  Google Scholar 

  49. Zhang D, Fong C, Jia Z, Liao C, Yao X, Yang M (2016) Icariin stimulates differentiation and suppresses adipocytic transdifferentiation of primary osteoblasts through estrogen receptor-mediated pathway. Calcif Tissue Int 99:1–12

    Article  PubMed  Google Scholar 

  50. Zhang J, Li Y, Sun J, Liu C, Zhang D (2011) Synergistic or antagonistic effect of MTE plus TF or icariin from Epimedium koreanum on the proliferation and differentiation of primary osteoblasts in vitro. Biol Trace Elem Res 143:1746–1757

    CAS  Article  PubMed  Google Scholar 

  51. Feng R, Feng L, Yuan Z, Wang D, Wang F, Tan B, Han S, Li T, Li D, Han Y (2013) Icariin protects against glucocorticoid-induced osteoporosis in vitro and prevents glucocorticoid-induced osteocyte apoptosis in vivo. Cell Biochem Biophys 67:189–197

    CAS  Article  PubMed  Google Scholar 

  52. Ma XN, Zhou J, Ge BF, Zhen P, Ma HP, Shi WG, Cheng K, Xian CJ, Chen KM (2013) Icariin induces osteoblast differentiation and mineralization without dexamethasone in vitro. Planta Med 79:1501–1508

    CAS  Article  PubMed  Google Scholar 

  53. Ma HP, Ma XN, Ge BF, Zhen P, Zhou J, Gao YH, Xian CJ, Chen KM (2014) Icariin attenuates hypoxia-induced oxidative stress and apoptosis in osteoblasts and preserves their osteogenic differentiation potential in vitro. Cell Prolif 47:527

    CAS  Article  PubMed  Google Scholar 

  54. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309

    CAS  Article  PubMed  Google Scholar 

  55. Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243

    CAS  Article  PubMed  Google Scholar 

  56. Zheng D, Peng S, Yang S-H, Shao Z-W, Yang C, Feng Y, Wu W, Zhen W-X (2012) The beneficial effect of icariin on bone is diminished in osteoprotegerin-deficient mice. Bone 51:85–92

    CAS  Article  PubMed  Google Scholar 

  57. Li XF, Xu H, Zhao YJ, Tang DZ, Xu GH, Holz J, Wang J, Cheng SD, Shi Q, Wang YJ (2013) Icariin augments bone formation and reverses the phenotypes of osteoprotegerin-deficient mice through the activation of Wnt/ β -catenin-BMP signaling. Evid Based Complement Alternat Med 2013(2013–11-4):652317

    PubMed  PubMed Central  Google Scholar 

  58. Hsieh TP, Sheu SY, Sun JS, Chen MH (2011) Icariin inhibits osteoclast differentiation and bone resorption by suppression of MAPKs/NF-κB regulated HIF-1α and PGE(2) synthesis. Phytomedicine 18:176

    CAS  Article  PubMed  Google Scholar 

  59. Chen KM, Ge BF, Liu XY, Ma PH, MB L, Bai MH, Wang Y (2007) Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture. Die Pharmazie 62:388–391

    CAS  PubMed  Google Scholar 

  60. Huang J, Yuan L, Wang X, Zhang TL, Wang K (2007) Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sci 81:832

    CAS  Article  PubMed  Google Scholar 

  61. Zhang D, Zhang J, Fong C, Yao X, Yang M (2012) Herba epimedii flavonoids suppress osteoclastic differentiation and bone resorption by inducing G2/M arrest and apoptosis. Biochimie 94:2514–2522

    CAS  Article  PubMed  Google Scholar 

  62. Huang J, Zhang JC, Zhang TL, Wang K (2007) Icariin suppresses bone resorption activity of rabbit osteoclasts in vitro. Chin Sci Bull 52:890–895

    CAS  Article  Google Scholar 

  63. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, Mccabe S (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402:304

    CAS  Article  PubMed  Google Scholar 

  64. Arron JR, Choi Y (2000) Osteoimmunology: bone versus immune system. Nature 408:535–536

    CAS  Article  PubMed  Google Scholar 

  65. Carlsten H (2005) Immune responses and bone loss: the estrogen connection. Immunol Rev 208:194–206

    CAS  Article  PubMed  Google Scholar 

  66. Chen CW, Dai QP, Fan TY, Chen YQ, Che T (2016) Icariin prevents cartilage and bone degradation in experimental models of arthritis. Mediat Inflamm 2016:1–10

    Google Scholar 

  67. Li X, Hu Y, He L, Wang S, Zhou H, Liu S (2012) Icaritin inhibits T cell activation and prolongs skin allograft survival in mice. Int Immunopharmacol 13:1

    Article  PubMed  Google Scholar 

  68. Shen R, Deng W, Li C, Zeng G (2015) A natural flavonoid glucoside icariin inhibits Th1 and Th17 cell differentiation and ameliorates experimental autoimmune encephalomyelitis. Int Immunopharmacol 24:224

    CAS  Article  PubMed  Google Scholar 

  69. Zhang G, Qin L, Shi Y (2007) Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res 22:1072

    CAS  Article  PubMed  Google Scholar 

  70. Castelo-Branco C, Figueras F, Sanjuan A, Vicente JJ, Mj MDO, Pons F, Balasch J, Vanrell JA (2000) Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of factors associated with discontinuation. Menopause 6:307–311

    Article  Google Scholar 

  71. Pilon D, Castilloux AM, Lelorier J (2001) Estrogen replacement therapy: determinants of persistence with treatment 1. Obstet Gynecol 97:97–100

    CAS  PubMed  Google Scholar 

  72. Min LU, Wang L, Luo Y (2013) Treatment of primary osteoporosis with epimedium total flavone capsule: a multicenter clinical observation on 360 cases. Chin J Osteoporos 19:279–274

    Google Scholar 

  73. Valdiviezo C, Lawson S, Ouyang P (2013) An update on menopausal hormone replacement therapy in women and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 20:148–155

    CAS  Article  PubMed  Google Scholar 

  74. Khastgir G, Studd J, Holland N, Alaghband-Zadeh J, Fox S, Chow J (2001) Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study. J Clin Endocrinol Metab 86:289–295

    CAS  PubMed  Google Scholar 

  75. Wei H, Zili L, Yuanlu C, Biao Y, Cheng L, Xiaoxia W, Yang L, Xing W (2011) Effect of icariin on bone formation during distraction osteogenesis in the rabbit mandible. Int J Oral Maxillofac Implants 40:413

    CAS  Article  Google Scholar 

  76. 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

    CAS  Article  PubMed  Google Scholar 

  77. Chen KM, Ge BF, Ma HP, Zheng RL (2004) The serum of rats administered flavonoid extract from Epimedium sagittatum but not the extract itself enhances the development of rat calvarial osteoblast-like cells in vitro. Pharmazie 59:61–64

    CAS  PubMed  Google Scholar 

  78. Xia Q, Xu D, Huang Z, Liu J, Wang X, Wang X, Liu S (2010) Preparation of icariside II from icariin by enzymatic hydrolysis method. Fitoterapia 81:437–442

    CAS  Article  PubMed  Google Scholar 

  79. Xia L, Li Y, Zhou Z, Dai Y, Liu H, Liu H (2013) Icariin delivery porous PHBV scaffolds for promoting osteoblast expansion in vitro. Mater Sci Eng C 33:3545–3552

  80. Li M, Gu Q, Chen M, Zhang C, Chen S, Zhao J (2017) Controlled delivery of icariin on small intestine submucosa for bone tissue engineering. Mater Sci Eng C 71:260

    CAS  Article  Google Scholar 

  81. Yan H, Zhou Z, Huang T, Peng C, Liu Q, Zhou H, Zeng W, Liu L, Ou B, He S (2016) Controlled release in vitro of icariin from gelatin/hyaluronic acid composite microspheres. Polym Bull 73:1–12

    Article  Google Scholar 

  82. Hallab NJ (2016) Biologic responses to orthopedic implants: innate and adaptive immune responses to implant debris. Spine 41(Suppl 7):S30

    Article  PubMed  Google Scholar 

  83. Urban RM, Hall DJ, Della VC, Wimmer MA, Jacobs JJ, Galante JO (2012) Successful long-term fixation and progression of osteolysis associated with first-generation cementless acetabular components retrieved post mortem. J Bone Joint Surg (Am Vol) 94:1877

    Article  Google Scholar 

  84. Cui J, Zhu M, Zhu S, Wang G, Xu Y, Geng D (2014) Inhibitory effect of icariin on Ti-induced inflammatory osteoclastogenesis. J Surg Res 192:447

    CAS  Article  PubMed  Google Scholar 

  85. Wang J, Tao Y, Ping Z, Zhang W, Hu X, Wang Y, Wang L, Shi J, Wu X, Yang H (2016) Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/β-catenin signaling pathway in vivo and in vitro. Sci Rep 6:23827

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  86. Zhang Y, Chen L, Liu C, Feng X, Wei L, Shao L (2016) Self-assembly chitosan/gelatin composite coating on icariin-modified TiO 2 nanotubes for the regulation of osteoblast bioactivity. Mater Des 92:471–479

    CAS  Article  Google Scholar 

  87. Zhang X, Guo Y, Li DX, Wang R, Fan HS, Xiao YM, Zhang L, Zhang XD (2011) The effect of loading icariin on biocompatibility and bioactivity of porous β-TCP ceramic. J Mater Sci Mater Med 22:371–379

    CAS  Article  PubMed  Google Scholar 

  88. Shen P, Wong SP, Yong EL (2007) Sensitive and rapid method to quantify icaritin and desmethylicaritin in human serum using gas chromatography–mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 857:47–52

    CAS  Article  PubMed  Google Scholar 

  89. Wong SP, Shen P, Lee L, Li J, Yong EL (2009) Pharmacokinetics of prenylflavonoids and correlations with the dynamics of estrogen action in sera following ingestion of a standardized Epimedium extract. J Pharm Biomed Anal 50:216

    CAS  Article  PubMed  Google Scholar 

  90. Chen Y, Zhao YH, Jia XB, Hu M (2008) Intestinal absorption mechanisms of prenylated flavonoids present in the heat-processed Epimedium koreanum Nakai (Yin Yanghuo). Pharm Res 25:2190

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. Meng FH, Li YB, Xiong ZL, Jiang ZM, Li FM (2005) Osteoblastic proliferative activity of Epimedium brevicornum Maxim. Phytomed Int J Phycol Phycochem 12:189–193

    CAS  Google Scholar 

  92. Xiao HH, Fung CY, Mok SK, Wong KC, Ho MX, Wang XL, Yao XS, Wong MS (2014) Flavonoids from Herba epimedii selectively activate estrogen receptor alpha (ERα) and stimulate ER-dependent osteoblastic functions in UMR-106 cells. J Steroid Biochem Mol Biol 143:141

    CAS  Article  PubMed  Google Scholar 

  93. Qi S, Zheng H (2017) Combined effects of phytoestrogen genistein and silicon on ovariectomy-induced bone loss in rat. Biol Trace Elem Res 177:281–287

    CAS  Article  PubMed  Google Scholar 

  94. Ma HP, Ming LG, Ge BF, Zhai YK, Song P, Xian CJ, Chen KM (2015) Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro. J Cell Biochem 112:916–923

    Article  Google Scholar 

  95. Turner RT, Maran A, Lotinun S, Hefferan T, Evans GL, Zhang M, Sibonga JD (2001) Animal models for osteoporosis. Rev Endocr Metab Disord 2:117

    CAS  Article  PubMed  Google Scholar 

  96. Turner RT (1999) Mice, estrogen, and postmenopausal osteoporosis. J Bone Miner Res 14:187–191

    CAS  Article  PubMed  Google Scholar 

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Funding

This work was supported by the Natural Science Foundation of China (81371989), Guangdong Science and Technology Department Project (2015A030313776, 2016A050503008), and the Shenzhen Municipal Science and Technology Innovation Committee Project (JSGG20150331154931068, JCYJ20160301151248779, JCYJ20160229172757249, CXZZ20151015151249563, and CXZZ20150401152251209).

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Wang, Z., Wang, D., Yang, D. et al. The effect of icariin on bone metabolism and its potential clinical application. Osteoporos Int 29, 535–544 (2018). https://doi.org/10.1007/s00198-017-4255-1

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Keywords

  • Bone metabolism
  • Icariin
  • Osteoblasts
  • Osteoclasts
  • Osteoporosis