Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Ethyl Acetate Extract of Poncirus trifoliata Fruit for Glucocorticoid-Induced Osteoporosis

  • Received : 2011.10.25
  • Accepted : 2011.11.02
  • Published : 2012.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Poncirus trifoliata fruit (PTF) affects the digestive and cardiovascular systems, and kidney function. The authors studied the effects of ethyl acetate (EtOAc) extract of PTF on the activities of osteoblasts and in an animal model. The main compounds of the EtOAc extract, naringin and poncirin have been confirmed by HPLC and NMR analysis. Effects of osteoblastic differentiation were measured by alkaline phosphatase (ALP) activity, osteopontin (OPN) protein expression and osteoprotegerin (OPG) mRNA expression in MC3T3-E1 cells. Also, osteoclast differentiation was measured by multinucleated cells (MNCs) formation through tartrate resistance acid phosphatase (TRAP)-positive staining. Bone mineral density (BMD) was measured before and after treatment with EtOAc extract of PTF in prednisolone-induced osteoporotic mice. Dexamethasone (DEX) decreased OPN and OPG expression level in MC3T3-E1 cells and ALP activity was decreased by DEX dose-dependently. EtOAc extract of PTF recovered the levels of ALP activity, and the expression of OPN and OPG in MC3T3-E1 cells treated with DEX. In osteoclast differentiation, multinucleated TRAP-positive cell formation was significantly suppressed by the EtOAc extract of PTF. Total body BMD was restored by EtOAc extract of PTF in prednisolone-induced osteoporotic mice. In conclusion, EtOAc extract of PTF recovered DEX-mediated deteriorations in osteoblastic and osteoclastic functions, and increased BMD in glucocorticoid-induced osteoporosis.

Keywords

References

  1. Audran, M. (2000) Raloxifene, selective estrogen receptor modulator (SERM). Introduction and conclusion. Joint. Bone. Spine. 67 Suppl 1, 3s-6s, 23s-25s.
  2. Bensky, D., Clavey, S., and Stoger, E. (2004). Herbs that regulate the Qi, Chinese Herbal Medicine: Materia Medica. Eastland Press Inc., Seattle.
  3. Boling, E. P. (2004) Secondary osteoporosis: underlying disease and the risk for glucocorticoid-induced osteoporosis. Clin. Ther. 26, 1-14. https://doi.org/10.1016/S0149-2918(04)90001-X
  4. Canalis, E. (1996) Clinical review 83: Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J. Clin. Endocrinol. Metab. 81, 3441-3447. https://doi.org/10.1210/jc.81.10.3441
  5. Chen, T. L. (2004) Inhibition of growth and differentiation of osteoprogenitors in mouse bone marrow stromal cell cultures by increased donor age and glucocorticoid treatment. Bone. 35, 83-95. https://doi.org/10.1016/j.bone.2004.03.019
  6. Cho, E. J., Piao, X., Piao, L., Piao, H., Park, M. K., Kim, B. K. and Park J. H. (2000) Chemical constituents of the fruit of Citrus junos. Nat. Prod. Sci. 6, 179-182.
  7. Ding, P., Tang, Q. and Chen, L. (2009) Effects of naringin on proliferation, differentiation and matrix mineralization of MC3T3-E1 cells. Zhongguo. Zhong. Yao. Za. Zhi. 34, 1712-1716.
  8. Fazzalari, N. L. (2008) Bone remodeling: a review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip. Semin. Cell. Dev. Biol. 19, 467-472. https://doi.org/10.1016/j.semcdb.2008.08.003
  9. Geusens, P. and Reid, D. (2005) Newer drug treatments: their effects on fracture prevention. Best. Pract. Res. Clin. Rheumatol. 19, 983-989. https://doi.org/10.1016/j.berh.2005.07.003
  10. Han, A. R., Kim, J. B., Lee, J., Nam, J. W., Lee, I. S., Shim, C. K., Lee, K. T. and Seo, E. K. (2007) A new flavanone glycoside from the dried immature fruits of Poncirus trifoliata. Chem. Pharm. Bull. (Tokyo). 55, 1270-1273. https://doi.org/10.1248/cpb.55.1270
  11. Katagiri, H. (2006) Active vitamin D and vitamin K as therapeutic agents for osteoporosis. Nihon. Rinsho. 64, 1639-1643.
  12. Kawaguchi, H., Manabe, N., Miyaura, C., Chikuda, H., Nakamura, K. and Kuro-o, M. (1999) Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J. Clin. Invest. 104, 229-237. https://doi.org/10.1172/JCI5705
  13. Khosla, S. (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology. 142, 5050-5055. https://doi.org/10.1210/en.142.12.5050
  14. Kim, D. H., Bae, E. A. and Han, M. J. (1999) Anti-Helicobacter pylori activity of the metabolites of poncirin from Poncirus trifoliata by human intestinal bacteria. Biol. Pharm. Bull. 22, 422-424. https://doi.org/10.1248/bpb.22.422
  15. Kim, H. J., Zhao, H., Kitaura, H., Bhattacharyya, S., Brewer, J. A., Muglia, L. J., Ross, F. P. and Teitelbaum, S. L. (2006) Glucocorticoids suppress bone formation via the osteoclast. J. Clin. Invest. 116, 2152-2160. https://doi.org/10.1172/JCI28084
  16. Kim, K. W., Suh, S. J., Lee, T. K., Ha, K. T., Kim, J. K., Kim, K. H., Kim, D. I., Jeon, J. H., Moon, T. C. and Kim, C. H. (2008) Effect of saffl ower seeds supplementation on stimulation of the proliferation, differentiation and mineralization of osteoblastic MC3T3-E1 cells. J. Ethnopharmacol. 115, 42-49. https://doi.org/10.1016/j.jep.2007.09.003
  17. Kim, B. Y., Yoon, H. Y., Yun, S. I., Woo, E. R., Song, N. K., Kim, H. G., Jeong, S. Y. and Chung, Y. S. (2011) In vitro and In vivo Inhibition of Glucocorticoid-induced Osteoporosis by the Hexane Extract of Poncirus trifoliata. Phytother. Res. 2011.
  18. Kulenovic, I., Rasic, S. and Kulenovic, E. (2006) Osteoporosis: current trends in diagnosis and management. Bosn. J. Basic. Med. Sci. 6, 24-28.
  19. Lane, N. E., Yao, W., Balooch, M., Nalla, R. K., Balooch, G., Habelitz, S., Kinney, J. H. and Bonewald, L. F. (2006) Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-defi cient mice. J. Bone. Miner. Res. 21, 466-476.
  20. Liu, J. C., Chan, P., Hsu, F. L., Chen, Y. J., Hsieh, M. H., Lo, M. Y. and Lin, J. Y. (2002) The in vitro inhibitory effects of crude extracts of traditional Chinese herbs on 3-hydroxy-3-methylglutaryl-coenzyme A reductase on Vero cells. Am. J. Chin. Med. 30, 629-636. https://doi.org/10.1142/S0192415X02000454
  21. Malluche, H. H., Koszewski, N., Monier-Faugere, M. C., Williams, J. P. and Mawad, H. (2006) Influence of the parathyroid glands on bone metabolism. Eur. J. Clin. Invest. 36 Suppl 2, 23-33. https://doi.org/10.1111/j.1365-2362.2006.01664.x
  22. Manolagas, S. C. (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev. 21, 115-137. https://doi.org/10.1210/er.21.2.115
  23. Meunier, P. J. (2001) Anabolic agents for treating postmenopausal osteoporosis. Joint. Bone. Spine. 68, 576-581. https://doi.org/10.1016/S1297-319X(01)00329-3
  24. Mundy, G. R. (2001) Statins and their potential for osteoporosis. Bone. 29, 495-497. https://doi.org/10.1016/S8756-3282(01)00606-8
  25. Neuprez, A., Hiligsmann, M., Scholtissen, S., Bruyere, O. and Reginster, J. Y. (2008) Strontium ranelate: the fi rst agent of a new therapeutic class in osteoporosis. Adv. Ther. 25, 1235-1256. https://doi.org/10.1007/s12325-008-0125-8
  26. O'Brien, C. A., Jia, D., Plotkin, L. I., Bellido, T., Powers, C. C., Stewart, S. A., Manolagas, S. C. and Weinstein, R. S. (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 145, 1835-1841. https://doi.org/10.1210/en.2003-0990
  27. Sato, M., Garsky, V., Majeska, R. J., Einhorn, T. A., Murray, J., Tashjian, A. H. Jr. and Gould, R. J. (1994) Structure-activity studies of the s-echistatin inhibition of bone resorption. J. Bone. Miner. Res. 9, 1441-1449.
  28. Schacke, H., Döcke, W. D. and Asadullah, K. (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol. Ther. 96, 23-43. https://doi.org/10.1016/S0163-7258(02)00297-8
  29. Shin, T. Y., Oh, J. M., Choi, B. J., Park, W. H., Kim, C. H., Jun, C. D. and Kim, S. H. (2006) Anti-infl ammatory effect of Poncirus trifoliata fruit through inhibition of NF-kappaB activation in mast cells. Toxicol. In. Vitro. 20, 1071-1076. https://doi.org/10.1016/j.tiv.2006.02.003
  30. Stein, G. S., Lian, J. B., Stein, J. L., Van Wijnen, A. J. and Montecino, M. (1996) Transcriptional control of osteoblast growth and differentiation. Physiol. Rev. 76, 593-629.
  31. Suh, S. J., Yun, W. S., Kim, K. S., Jin, U. H., Kim, J. K., Kim, M. S., Kwon, D. Y. and Kim, C. H. (2007) Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic MC3T3-E1 cells. J. Ethnopharmacol. 109, 480-485. https://doi.org/10.1016/j.jep.2006.08.030
  32. Turner, C. H. (1991) Toward a cure for osteoporosis: reversal of excessive bone fragility. Osteoporos. Int. 2, 12-19. https://doi.org/10.1007/BF01627073
  33. Walsh, L. J., Wong, C. A., Pringle, M. and Tattersfi eld, A. E. (1996) Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. BMJ. 313, 344-346. https://doi.org/10.1136/bmj.313.7053.344
  34. Wei, M., Yang, Z., Li, P., Zhang, Y. and Sse, W. C. (2007) Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model. Am. J. Chin. Med. 35, 663-667. https://doi.org/10.1142/S0192415X07005156
  35. Weinstein, R. S., Chen, J. R., Powers, C. C., Stewart, S. A., Landes, R. D., Bellido, T., Jilka, R. L., Parfi tt, A. M. and Manolagas, S. C. (2002) Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J. Clin. Invest. 109, 1041-1048. https://doi.org/10.1172/JCI0214538
  36. Weinstein, R. S., Jilka, R. L., Parfi tt, A. M. and Manolagas, S. C. (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J. Clin. Invest. 102, 274-282. https://doi.org/10.1172/JCI2799
  37. Yeung, H. C. (1985). An excellent Chinese herbal giving information on over 500 species. Rather technical and probably best suited to the more accomplished user of herbs. Handbook of Chinese Herbs and Formulas. Institute of Chinese Medicine, Los Angeles.
  38. Yoon, H. Y., Yun, S. I., Kim, B. Y., Jin, Q., Woo, E. R., Jeong, S. Y. and Chung, Y. S. (2011) Poncirin promotes osteoblast differentiation but inhibits adipocyte differentiation in mesenchymal stem cells. Eur. J. Pharmacol. 664, 54-59. https://doi.org/10.1016/j.ejphar.2011.04.047
  39. Zhang, P., Dai, K. R., Yan, S. G., Yan, W. Q., Zhang, C., Chen, D. Q., Xu, B. and Xu, Z. W. (2009) Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. Eur. J. Pharmacol. 607, 1-5. https://doi.org/10.1016/j.ejphar.2009.01.035

Cited by

  1. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone vol.6, pp.1, 2016, https://doi.org/10.1038/srep24562
  2. Effect of glucocorticoid withdrawal on glucocorticoid inducing bone impairment vol.477, pp.4, 2016, https://doi.org/10.1016/j.bbrc.2016.07.036
  3. Icariin protects against glucocorticoid induced osteoporosis, increases the expression of the bone enhancer DEC1 and modulates the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway vol.136, 2017, https://doi.org/10.1016/j.bcp.2017.04.010
  4. Simultaneous Determination and Optimization Ultrasound-Assisted Extraction of Poncirin and Naringin in Poncirus trifoliata Rafinesqul vol.22, pp.2, 2014, https://doi.org/10.7783/KJMCS.2014.22.2.147
  5. Effect of Pulsed Electromagnetic Field on Bone Formation and Lipid Metabolism of Glucocorticoid-Induced Osteoporosis Rats through Canonical Wnt Signaling Pathway vol.2016, 2016, https://doi.org/10.1155/2016/4927035
  6. Controlled Release of Naringin in Metal-Organic Framework-Loaded Mineralized Collagen Coating to Simultaneously Enhance Osseointegration and Antibacterial Activity vol.9, pp.23, 2017, https://doi.org/10.1021/acsami.7b05296
  7. Involvement of periostin–sclerostin–Wnt/β-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin vol.468, pp.4, 2015, https://doi.org/10.1016/j.bbrc.2015.10.152
  8. Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities ofTephrosia humilisaerial parts’ extracts vol.30, pp.12, 2016, https://doi.org/10.1080/14786419.2015.1057729
  9. Therapeutic potential of naringin: an overview vol.54, pp.12, 2016, https://doi.org/10.1080/13880209.2016.1216131
  10. (L.) Raf. on cancer, inflammation, and digestive dysfunction vol.32, pp.4, 2017, https://doi.org/10.1002/ptr.6008
  11. Limethason reduces airway inflammation in a murine model of ovalbumin-induced chronic asthma without causing side effects vol.15, pp.3, 2012, https://doi.org/10.3892/etm.2018.5691