Effect of diosgenin, a steroidal sapogenin, on the rat skeletal system

• Authors: Joanna Folwarczna , Maria Zych , Barbara Nowińska , Maria Pytlik , Magdalena Bialik , Anna Jagusiak , Maria Lipecka-Karcz , Michał Matysiak
• Languages of publication: EN

Abstracts

EN

Diosgenin is a steroidal sapogenin present in fenugreek and Dioscorea spp. as glycosides (saponins). Diosgenin has already been reported to inhibit osteoclastogenesis and to stimulate osteogenic activity of osteoblastic cells in vitro, and to exert some antiosteoporotic effects in rats in vivo. The aim of the present study was to investigate the effects of diosgenin administration on the skeletal system of rats with normal estrogen level and with estrogen deficiency induced by bilateral ovariectomy. The experiments were carried out on 3-month-old non-ovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving diosgenin (50 mg/kg p.o. daily) for 4 weeks. Serum bone turnover markers, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diosgenin improved some investigated parameters in both non-ovariectomized and ovariectomized rats, in which estrogen deficiency induced osteoporotic changes. Diosgenin increased compact bone formation and probably inhibited cancellous bone resorption, which led to improvement of mechanical properties of compact and cancellous bone. In conclusion, this in vivo study demonstrated that diosgenin may be one of sparse compounds increasing bone formation.

Keywords

EN

diosgenin; skeletal system; osteoporosis; estrogen deficiency; rats

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2016
• Volume: 63
• Issue: 2
• Pages: 287-295

Dates

published

2016

received

2015-07-15

revised

2015-11-30

accepted

2016-02-28

(unknown)

2016-04-26

Contributors

author

Joanna Folwarczna

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Maria Zych

• Department of Pharmacognosy and Phytochemistry, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Barbara Nowińska

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Maria Pytlik

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Magdalena Bialik

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Anna Jagusiak

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Maria Lipecka-Karcz

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

author

Michał Matysiak

• Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Katowice, Poland

References

• Alcantara EH, Shin MY, Sohn HY, Park YM, Kim T, Lim JH, Jeong HJ, Kwon ST, Kwun IS (2011) Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells. J Nutr Biochem 22: 1055-1063. doi: 10.1016/j.jnutbio.2010.09.003.
• Au AL, Kwok CC, Lee AT, Kwan YW, Lee MM, Zhang RZ, Ngai SM, Lee SM, He GW, Fung KP (2004) Activation of iberiotoxin-sensitive, Ca2+-activated K+ channels of porcine isolated left anterior descending coronary artery by diosgenin. Eur J Pharmacol 502: 123-133. doi: 10.1016/j.ejphar.2004.08.045.
• Cayen MN, Dvornik D (1979) Effect of diosgenin on lipid metabolism in rats. J Lipid Res 20: 162-174. Available at: http://www.jlr.org/content/20/2/162.long
• Chang CC, Kuan TC, Hsieh YY, Ho YJ, Sun YL, Lin CS (2011) Effects of diosgenin on myometrial matrix metalloproteinase-2 and -9 activity and expression in ovariectomized rats. Int J Biol Sci 7: 837-847. doi: 10.7150/ijbs.7.837.
• Chen PS, Shih YW, Huang HC, Cheng HW (2011) Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS One 6: e20164. doi: 10.1371/journal.pone.0020164.
• Chiang SS, Chang SP, Pan TM (2011) Osteoprotective effect of Monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis. J Agric Food Chem 59: 9150-9157. doi: 10.1021/jf201640j.
• Chiang SS, Pan TM (2013) Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health. Appl Microbiol Biotechnol 97: 1489-1500. doi: 10.1007/s00253-012-4675-y.
• Depypere HT, Comhaire FH (2014) Herbal preparations for the menopause: beyond isoflavones and black cohosh. Maturitas 77: 191-194. doi: 10.1016/j.maturitas.2013.11.001.
• Dias KL, Correia Nde A, Pereira KK, Barbosa-Filho JM, Cavalcante KV, Araújo IG, Silva DF, Guedes DN, Neto Mdos A, Bendhack LM, Medeiros IA (2007) Mechanisms involved in the vasodilator effect induced by diosgenin in rat superior mesenteric artery. Eur J Pharmacol 574: 172-178. doi: 10.1016/j.ejphar.2007.07.017.
• Folwarczna J, Janiec W, Barej M, Cegieła U, Pytlik M, Kaczmarczyk-Sedlak I (2004) Effects of nadroparin on bone histomorphometric parameters in rats. Pol J Pharmacol 56: 337-343. Available at: http://www.rabbit.if-pan.krakow.pl/pjp/pdf/2004/3_337.pdf.
• Folwarczna J, Pytlik M, Zych M, Cegieła U, Kaczmarczyk-Sedlak I, Nowińska B, Śliwiński L (2013) Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats. Mol Nutr Food Res 57: 1772-1784. doi: 10.1002/mnfr.201300123.
• Folwarczna J, Pytlik M, Zych M, Cegieła U, Nowinska B, Kaczmarczyk-Sedlak I, Śliwinski L, Trzeciak H, Trzeciak HI (2015) Effects of caffeic and chlorogenic acids on the rat skeletal system. Eur Rev Med Pharmacol Sci 19: 682-693. Available at: http://www.europeanreview.org/article/8588.
• Folwarczna J, Zych M, Nowińska B, Pytlik M (2014a) Effects of fenugreek (Trigonella foenum-graecum L.) seed on bone mechanical properties in rats. Eur Rev Med Pharmacol Sci 18: 1937-1947. Available at: http://www.europeanreview.org/article/7577.
• Folwarczna J, Zych M, Nowińska B, Pytlik M, Janas A (2014b) Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek, on bone mechanical properties in estrogen-deficient rats. Mol Nutr Food Res 58: 1457-1464. doi: 10.1002/mnfr.201300936.
• Francis G, Kerem Z, Makkar HP, Becker K (2002) The biological action of saponins in animal systems: a review. Br J Nutr 88: 587-605. doi: 10.1079/BJN2002725.
• Higdon K, Scott A, Tucci M, Benghuzzi H, Tsao A, Puckett A, Cason Z, Hughes J (2001) The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model. Biomed Sci Instrum 37: 281-286.
• Jung DH, Park HJ, Byun HE, Park YM, Kim TW, Kim BO, Um SH, Pyo S (2010) Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-kappaB and AP-1 activation. Int Immunopharmacol 10: 1047-1054. doi: 10.1016/j.intimp.2010.06.004.
• Kim DS, Jeon BK, Lee YE, Woo WH, Mun YJ (2012) Diosgenin induces apoptosis in HepG2 cells through generation of reactive oxygen species and mitochondrial pathway. Evid Based Complement Alternat Med 2012: 981675. doi: 10.1155/2012/981675.
• Lecka-Czernik B (2010) Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary osteoporosis. Curr Osteoporos Rep 8: 178-184. doi: 10.1007/s11914-010-0027-y.
• Liu Z, Gao W, Jing S, Zhang Y, Man S, Wang Y, Zhang J, Liu C (2013) Correlation among cytotoxicity, hemolytic activity and the composition of steroidal saponins from Paris L. J Ethnopharmacol 149: 422-430. doi: 10.1016/j.jep.2013.06.033.
• Manda VK, Avula B, Ali Z, Wong YH, Smillie TJ, Khan IA, Khan SI (2013) Characterization of in vitro ADME properties of diosgenin and dioscin from Dioscorea villosa. Planta Med 79: 1421-1428. doi: 10.1055/s-0033-1350699.
• 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. doi: 10.1038/nrendo.2013.179.
• Medigović I, Ristić N, Živanović J, Šošić-Jurjević B, Filipović B, Milošević V, Nestorović N (2014) Diosgenin does not express estrogenic activity: a uterotrophic assay. Can J Physiol Pharmacol 92: 292-298. doi: 10.1139/cjpp-2013-0419.
• Okawara M, Tokudome Y, Todo H, Sugibayashi K, Hashimoto F (2013) Enhancement of diosgenin distribution in the skin by cyclodextrin complexation following oral administration. Biol Pharm Bull 36: 36-40. doi: 10.1248/bpb.b12-00467.
• Patel K, Gadewar M, Tahilyani V, Patel DK (2012) A review on pharmacological and analytical aspects of diosgenin: a concise report. Nat Prod Bioprospect 2: 46-52. doi: 10.1007/s13659-012-0014-3.
• Qu X, Zhai Z, Liu X, Li H, Ouyang Z, Wu C, Liu G, Fan Q, Tang T, Qin A, Dai K (2014) Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades. Biochem Biophys Res Commun 443: 658-665. doi: 10.1016/j.bbrc.2013.12.029.
• Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377: 1276-1287. doi: 10.1016/S0140-6736(10)62349-5.
• Rajput S, Mandal M (2012) Antitumor promoting potential of selected phytochemicals derived from spices: a review. Eur J Cancer Prev 21: 205-215. doi: 10.1097/CEJ.0b013e32834a7f0c.
• Raju J, Mehta R (2009) Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin. Nutr Cancer 61: 27-35. doi: 10.1080/01635580802357352.
• Sangeetha MK, ShriShri Mal N, Atmaja K, Sali VK, Vasanthi HR (2013) PPAR's and diosgenin a chemico biological insight in NIDDM. Chem Biol Interact 206: 403-410. doi: 10.1016/j.cbi.2013.08.014.
• Sato K, Fujita S, Iemitsu M (2014) Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats. J Steroid Biochem Mol Biol 143: 152-159. doi: 10.1016/j.jsbmb.2014.02.020.
• Sausbier U, Dullin C, Missbach-Guentner J, Kabagema C, Flockerzie K, Kuscher GM, Stuehmer W, Neuhuber W, Ruth P, Alves F, Sausbier M (2011) Osteopenia due to enhanced cathepsin K release by BK channel ablation in osteoclasts. PLoS One 6: e21168. doi: 10.1371/journal.pone.0021168.
• Scott A, Higdon K, Tucci M, Benghuzzi H, Puckett A, Tsao A, Cason Z, Hughes J (2001) The prevention of osteoporotic progression by means of steroid loaded TCPL drug delivery systems. Biomed Sci Instrum 37: 13-18.
• Shishodia S, Aggarwal BB (2006) Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IkappaB kinase activation and NF-kappaB-regulated gene expression. Oncogene 25: 1463-1473. doi: 10.1038/sj.onc.1209194.
• Stürmer EK, Seidlová-Wuttke D, Sehmisch S, Rack T, Wille J, Frosch KH, Wuttke W, Stürmer KM (2006) Standardized bending and breaking test for the normal and osteoporotic metaphyseal tibias of the rat: effect of estradiol, testosterone, and raloxifene. J Bone Miner Res 21: 89-96. doi: 10.1359/JBMR.050913.
• Tella SH, Gallagher JC (2014) Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol 142: 155-170. doi: 10.1016/j.jsbmb.2013.09.008.
• Tikhonova MA, Ting CH, Kolosova NG, Hsu CY, Chen JH, Huang CW, Tseng GT, Hung CS, Kao PF, Amstislavskaya TG, Ho YJ (2015) Improving bone microarchitecture in aging with diosgenin treatment: A study in senescence-accelerated OXYS rats. Chin J Physiol 58: 322-331. doi: 10.4077/CJP.2015.BAD325.
• Turner CH, Burr DB (1993) Basic biomechanical measurements of bone: a tutorial. Bone 14: 595-608. doi: 10.1016/8756-3282(93)90081-K.
• Uemura T, Hirai S, Mizoguchi N, Goto T, Lee JY, Taketani K, Nakano Y, Shono J, Hoshino S, Tsuge N, Narukami T, Takahashi N, Kawada T (2010) Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Mol Nutr Food Res 54: 1596-1608. doi: 10.1002/mnfr.200900609.
• Wang L, Wang YD, Wang WJ, Zhu Y, Li DJ (2007) Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor. J Mol Endocrinol 38: 467-479. doi: 10.1677/jme.1.02173.
• Yen ML, Su JL, Chien CL, Tseng KW, Yang CY, Chen WF, Chang CC, Kuo ML (2005) Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts. Mol Pharmacol 68: 1061-1073. doi: 10.1124/mol.104.010082.
• Yin J, Han N, Liu Z, Song S, Kadota S (2010) The in vitro antiosteoporotic activity of some glycosides in Dioscorea spongiosa. Biol Pharm Bull 33: 316-320. doi: 10.1248/bpb.33.316.
• Yin J, Tezuka Y, Kouda K, Le Tran Q, Miyahara T, Chen Y, Kadota S (2004) In vivo antiosteoporotic activity of a fraction of Dioscorea spongiosa and its constituent, 22-O-methylprotodioscin. Planta Med 70: 220-226. doi: 10.1055/s-2004-815538.
• Zhang Z, Song C, Fu X, Liu M, Li Y, Pan J, Liu H, Wang S, Xiang L, Xiao GG, Ju D (2014a) High-dose diosgenin reduces bone loss in ovariectomized rats via attenuation of the RANKL/OPG ratio. Int J Mol Sci 15: 17130-17147. doi: 10.3390/ijms150917130.
• Zhang Z, Xiang L, Bai D, Fu X, Wang W, Li Y, Liu H, Pan J, Li Y, Xiao GG, Ju D (2014b) Treatment with Rhizoma Dioscoreae extract has protective effect on osteopenia in ovariectomized rats. Scientific World Journal 2014: 645975. doi: 10.1155/2014/645975.
• Zhao S, Niu F, Xu CY, Liu Y, Ye L, Bi GB, Chen L, Tian G, Nie TH (2015) Diosgenin prevents bone loss on retinoic acid-induced osteoporosis in rats. Ir J Med Sci [Epub ahead of print] doi: 10.1007/s11845-015-1309-2.

Identifiers

DOI

10.18388/abp.2015_1095