The effect of combined Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max (OPB) extracts on bone mineral density in ovariectomized rats.

  • Kim, Jung-Keun (Dept. of Pharmacology and Mechanism, Research Institute, Oscotec Inc.) ;
  • Kim, Se-Won (Dept. of Pharmacology and Mechanism, Research Institute, Oscotec Inc.) ;
  • Ko, Seon-Yle (Dept. of Pharmacology and Mechanism, Research Institute, Oscotec Inc.) ;
  • Kim, Se-Nyun (Dept. of Pharmacology and Mechanism, Research Institute, Oscotec Inc.) ;
  • Kwon, Jong-Seok (Dept. of Pharmacology and Mechanism, Research Institute, Oscotec Inc.) ;
  • Hwang, Hyeon-Hwan (Dept. of Safety and Toxicology, Research Institute, Oscotec. Inc.)
  • Published : 2007.12.31

Abstract

This study was conducted to investigate the preventing effects of OPB (Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max extracts) and combined OPB/Calcium therapy on bone loss in ovariectomized rats. Sixty Sprague Dawley rats of 12-week-old were divided into eight groups: OVX (ovariectomized), OPBL (OPB 50 mg/kg), OPBM (OPB100 mg/kg), OPBH (OPB 200 mg/kg), OPBL/CAL(OPBL+CAL), OPBM/CAL (OPBM+CAL), OPBH/CAL (OPBH+CAL) and CAL (Calcium citrate 88.33 mg/kg+1$\alpha$, 25-dihydroxy-vitamin $D_3$ 33.33 IU/kg). Bone mineral density (BMD), bone mineral content (BMC), bone strength indices and cortical thickness were analyzed by peripheral quantitative computerized tomography (pQCT). pQCT scanning showed that OVX induced a significant decrease in trabecular bone mineral density and bone mineral content in the proximal tibia $(-36.4\pm2.4%,\;-21.8\pm12.7%)$. These decreases were significantly prevented by the administration of OPBM and OPBM/CAL. Cortical BMD and BMC of tibia were slightly enhanced by OPB and OPB/CAL. However there was no significant difference between OVX and OPB, OPB/CAL treated group. Bone strength indices and cortical thickness were not significantly different. Our results suggest that OPB and combined OPB/Calcium therapy are effective in preventing the development of bone loss induced by ovariectomy in rats.

Keywords

References

  1. Albright, F., Smith, P. H. and Richardson, A. M.: Postmenopausal osteoporosis: clinical features. J. Am. Med. Ass. 116:2465-2474, 1941 https://doi.org/10.1001/jama.1941.02820220007002
  2. Ammann, P., Rizzoli, R., Muler, K., Slosman D. and Bonjour J. P.: IGF-I and Pamidronate increase bone mineral density in ovariectomized adult rats. Am. Physiol. Soc. E770-776, 1993
  3. Ash, S. L. and Goldin, B. R.: Effect of age and estrogen on renal vitamin D metabolism in female rats. Am. J. Clin. Nutr. 47:694-699, 1988 https://doi.org/10.1093/ajcn/47.4.694
  4. Austin, L.A. and Health, H.: Calcitonin: physiology and pathophysiology. N. Engl. J. Med. 304:269-278, 1981 https://doi.org/10.1056/NEJM198101293040505
  5. Awang, D.V.C.: Siberian ginseng toxicity may be a case of mistaken identity. Can. Med. Assoc. J. 155:1237, 1996
  6. Ben-Hur, E. and Fulder, S.: Effect of Panax ginseng saponins and Eleutherococcus senticosus on survival of cultured mammalian cells after ionizing radiation. Am. J. Chin. Med. 9:48-56, 1981 https://doi.org/10.1142/S0192415X8100007X
  7. Chao, J.C., Chiang, S.W., Wang, C.C., Tsai, Y.H. and Wu, M.S.: Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J. Gastroenterol. 12:4478-4484, 2006 https://doi.org/10.3748/wjg.v12.i28.4478
  8. Cruess, R.L. and Hong, K.C.: The effect of long term estrogen administration on bone metabolism in the female rat. Endocrinology. 104:1188-1193, 1979 https://doi.org/10.1210/endo-104-4-1188
  9. Fujikawa, T., Yamaguchi, A., Morita, I., Takeda, H. and Nishibe, S.: Protective effects of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats. Biol. Pharm. Bull. 19:1227-1230, 1996 https://doi.org/10.1248/bpb.19.1227
  10. Gamero, P. and Delmas, P.D.: New development in biochemical markers for osteoporosis. Calcif. Tissue Int. 54(Suppl 1):S2-9, 1996
  11. Gamero, P., Sornay-Rendu, E., Chapuy, M.C. and Delmas, P.D.: Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res. 13(3):337-349, 1996
  12. Gasser, J.A: Quantitative assessment of bone mass and geometry by pQCT in rats in vivo and site specificity of changes at different skeletal sites. J. Jpn. Soc. Bone Morphom. 7:107-114, 1997
  13. Harrison, M. and Fraser, R.: Calcium metabolism in osteoporosis. Lancet. 1:1015-1019, 1961
  14. Hough, S.: Fast and slow bone losers. Relevance to the management of osteoporosis. Drug Aging. 12(Suppl 1):1-7, 1998
  15. Jin, U.H., Kim, D.I., Lee, T.K, Lee, D.N., Kim, J.K, Lee, I.S. and Kim, C.H.: Herbal formulation, Yukmi-jihang-tang-Jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression. J. Ethnopharmacol. 106:333-343, 2006 https://doi.org/10.1016/j.jep.2006.01.012
  16. Kalu, D.N., Hardin, R.R. and Cockerham, R.: Evaluation of the pathogenesis of skeletal changes in ovariectomized rats. Endocr. 115:507-512, 1984 https://doi.org/10.1210/endo-115-2-507
  17. Kim, J.K., Kim, S.W., Kim, H.Y., Lee, B.E., Hwamg, H.H., Kwon, J.S. and Ko, S.Y.: 숙지황과 기시오가피 복합추출물 (OPB) 이 난소절제 흰쥐의 골밀도 및 골대사에 미치는 영향. 대한구강내과학회지. 32:35-43, 2007
  18. Kim, J.K., Kim, S.W., Kim, H.Y., Lee, B.E and Ko, S.Y.: OPB, a water extract from Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max, inhibits osteoclast differentiation and function. Int. J. Oral Biol. 31 :23-24, 2007
  19. Kim, S.S., Son, Y.O., Chun, J.C., Kim, S.E., Chung, G.H., Hwang, K.J. and Lee, J.C.: Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glutinosa. Redox. Rep. 10:311-318, 2005 https://doi.org/10.1179/135100005X83734
  20. Kimmel, D.B: Animal models for in vivo experimentation in osteoporosis research. Osteoporosis, Academic press. 671-690, 1996
  21. Kormosh, N., Laktionov, K. and Antoshechkina, M.: Effect of a combination of extract from several plants on cellmediated and humoral immunity of patients with advanced ovarian cancer. Phytother. Res. 20:424-425, 2006 https://doi.org/10.1002/ptr.1889
  22. Lane, J.M. and Nydick, M.: Osteoporosis: current modes of prevention and treatment. J. Am. Acad. Orthop. Surg. 7(1): 19-31, 1999 https://doi.org/10.5435/00124635-199901000-00003
  23. Orimo, H., Fujita, T. and Yoshikawa. M.: Increased sensitivity of bone to parathyroid hormone in ovariectomized rats. Endocrinology. 90:760-763, 1972 https://doi.org/10.1210/endo-90-3-760
  24. Raju, B.L., Lin, S.J., Hou, W.C., Lai, A.Y., Liu, P.C. and Hsu, F.L.: Antioxidant iridoid glucosides from Wendlandia formosana, Natural Product Res. 8:357-364, 2004
  25. Recker, R.P.: Current therapy for osteoporosis. J. Clin. Endocrinol. Metab. 76:14-16, 1993 https://doi.org/10.1210/jc.76.1.14
  26. Reginster, J.Y.: Treatment of bone in elderly subjects: calcium, vitamin D, fluor, bisphosphonates, calcitonin. Horm. Res. 43:83-88, 1995 https://doi.org/10.1159/000184243
  27. Rodan, G.A.: Emerging therapies in osteoporosis. Ann. Rep. Med. Chem. 29:275-285, 1994 https://doi.org/10.1016/S0065-7743(08)60741-1
  28. Sato, M. and Grasser, W.: Effect of bisphosphonate on isolated rat osteoclasts as examined by reflected light microscopy. J. Bone Miner. Res. 5:31-40, 1990 https://doi.org/10.1002/jbmr.5650050107
  29. Shan, B.E., Yoshita, Y., Sugiura, T. and Yamashita, D.: Suppressive effect of Chinese medicinal herb, Acanthopanax gracilistylus, extract on human lympocytes in vitro. Clin. Exp. Immunol. 118:41-48, 1999 https://doi.org/10.1046/j.1365-2249.1999.01031.x
  30. Shen, M.L., Zhai, S.K., Chen, H.L., Luo, Y.D., Tu, G.R. and Ou, D.W.: Immunopharmacological effects of polysaccharides from Acanthopanax senticosus on experimental animals. Int. J. Immunophannacol. 13:549-554, 1991 https://doi.org/10.1016/0192-0561(91)90075-I
  31. Sridhar, C., Subbaraju, G. V., Venkateswarlu, Y. and Venugopal, P.T.: New acylated iridoid glucosides from Vitex altissima. J. Natural Products. 67:2012-2016, 2004 https://doi.org/10.1021/np040117r
  32. Stock, J.L.: Drug therapy in Osteoporosis: Diagnostic and Therapeutic Principles, edited by Rosen, C.J., Totowa, N.J., Humana Press. 173-187, 1996
  33. Takahashi, N., Akastu, T, Sasaki, T, Nicholson, G.C., Moseley, J.M., Martin, T.J. and Suda, T.: Induction of calcitonin receptors by la, 25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells. Endocrinol. 123:1504-1510, 1988 https://doi.org/10.1210/endo-123-3-1504
  34. Takahashi, N., Yamana, H., Yoshiki, S., Roodman, G.D., Mundy, G.R., Jones, S.J., Boyde, A. and Suda, T.: Osteoclastlike cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinol. 122: 1373-1382, 1988 https://doi.org/10.1210/endo-122-4-1373
  35. Takasugi, N., Moriguchi, T., Fuwa, T., Sanada, S., Ida, Y., Shofi, J. and Saito, H.: Effect of Eleutherococcus senticosus and its rectal temperature, body and grip tones, mortor coordination, and exploratory and spontaneous movements in acute stressed mice. Shoyakugaku Zasshi. 39:232-237, 1985
  36. Tang, W. and Eisenbrand, G.: Chinese Drugs of Plant Origin: in Chemistry, Pharmacolgy, and Use in Traditional Modern Medicine, Berlin, Springer-Verlag. 849-854, 1992
  37. Wang, J.Z., Mao, X.J., Ito, H. and Shimura, K.: Immunomodulatory activity of polysaccharide from Acanthopanax obovatus roots. Planta. Med. 57:335-336, 1991 https://doi.org/10.1055/s-2006-960111
  38. Wang, J.Z., Tsumura, H., Shimura, K. and Ito, H.: Antitumor activity of polysaccharide form a Chinese medicinal herb, Acnthopanax giraldii Harms. Cancer Lett. 65:79-84, 1992 https://doi.org/10.1016/0304-3835(92)90216-I
  39. Wasnich, R.: What is an osteoporotic fracture in Osteoporosis: Diagnostic and Therapeutic Principles, edited by Rosen, C.J., Totowa, N.J., Humana Press. 79-88, 1996
  40. Wronski, T. J., Clintron, M., Doherty, A. L. and Dann, L. M.: Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology. 123:681-686, 1988 https://doi.org/10.1210/endo-123-2-681
  41. Yu, H.H., Seo, S.J., Kim, Y.H. and Lee, H.Y., Park, R.K., So, H.S., Jang, S.L. and You, Y.O.: Protective effect of Rehmannia glutinosa on the cisplatin-induced damage of HEI-OCl auditory cells through scavenging free radicals. J. Ethnopharmacol. 107:383-388, 2006 https://doi.org/10.1016/j.jep.2006.03.024
  42. Zhao, Y., Wen, X.S., Cui, J. and Wu, W.H.: Extraction and salting-out purification of alpha-galactosidase and betaglucosidase from fresh roots of Rehmannia glutinosa. Zhong. Yao. Cai. 29:137-139, 2006
  43. 生藥學硏究會 : 현대생약학, 236-265, 1998
  44. 小學館, 中藥大辭典(제2권) 350, 1985
  45. 辛民敎, 原色臨床本草學, 南山堂, 218, 1986