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Effects of Lycii Fructus and Lycii Folium Extracts on Osteoporosis in Ovariectomized Rats

구기자와 구기엽 추출물이 난소적출 흰쥐의 골다공증에 미치는 영향

  • Kim, Jin-Ho (Dept. of Anatomy, College of Korean Medicine, Dongshin University) ;
  • Kim, Jeong-Sang (Dept. of Anatomy, College of Korean Medicine, Dongshin University)
  • 김진호 (동신대학교 한의과대학 해부학교실) ;
  • 김정상 (동신대학교 한의과대학 해부학교실)
  • Received : 2013.09.02
  • Accepted : 2013.10.14
  • Published : 2014.01.31

Abstract

The effects of Lycii fructus and Lycii folium on osteoporosis and serum cholesterol levels were tested in ovariectomized (OVX) rats. Twenty-four female Sprague-Dawley rats were divided into four groups: Sham group (sham-operated), Control group (OVX, ovariectomized model), LCF group (Ovx+Lycii fructus extract), and LCL group (OVX+Lycium folium extract). After 8 weeks, the OVX ($330{\pm}5.39$ g), LCF ($315{\pm}2.99$ g), and LCL ($318{\pm}2.06$ g) groups showed increased body weight compared with sham group ($281{\pm}1.71$ g). The levels of serum osteocalcin (OC) also increased in the LCF ($444.6{\pm}26.9$ ng/mL) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($107{\pm}3.52$ ng/mL). The activities of serum alkaline phosphatase (ALP) increased in the LCF ($108{\pm}2.7$ U/L) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($95{\pm}2.9$ U/L). Stereomicroscopy found that the low bone density that developed in the OVX group was significantly reversed in the LCF and LCL groups after 8 weeks. We also obtained molecular-based in vivo evidence that supports a mechanism of action involving novel estrogen receptor ($ER{\alpha}$) modulator in the uterus. We found that expression of ER${\alpha}$ mRNA in the OVX rat uterus was elevated by Lycium chinense. These results suggest that Lycii fructus and Lycii folium administered to rats during 8 weeks after oophorectomy may partially recover postmenopausal osteoporosis or delay the progression of osteoporotic changes.

본 연구는 구기자와 구기엽 추출물이 난소를 절제한 흰쥐의 체중 증가, 골밀도, 에스트로겐 수용체의 발현에 미치는 영향을 밝히고자 시행하였다. 실험군은 흰쥐 24마리를 가장수술군(Sham군), 난소를 절제한 대조군(OVX군), 난소절제 후 구기자 추출액을 투여한 군(LCF군), 난소절제 후 구기엽 추출액을 투여한 군(LCL군)으로 구분하였다. 8주 후 난소를 절제한 OVX군($330{\pm}5.39g$), LCF군($315{\pm}2.99g$) 및 LCL군($318{\pm}2.06g$)의 체중은 Sham군($281{\pm}1.71g$)에 비하여 증가하였다. 혈청 osteocalcin 활성은 OVX군($107{\pm}3.52ng/mL$)에 비하여 LCF군($444.6{\pm}26.9ng/mL$)과 LCL군($407{\pm}18.9ng/mL$)에서 증가하였다. Alkaline phosphatase의 활성은 OVX군($95{\pm}2.9U/L$)에 비하여 LCF군($108{\pm}2.7U/L$)과 LCL군($407{\pm}18.9ng/mL$)에서 증가하였다. 8주 후 넙다리뼈를 실체현미경으로 관찰한 결과 뼈 기질밀도는 난소절제군에서 감소하였으나, 구기자와 구기엽을 추출액을 투여한 군에서는 뚜렷이 회복되었다. 에스트로겐 수용체의 mRNA 발현은 OVX군에서는 거의 발현되지 않았으나, LCF군과 LCL군에서 뚜렷이 증가하였다. 이상의 결과로 보아 구기자와 구기엽 물추출물이 난소절제에 의하여 유발된 흰쥐의 뼈 기질 회복 또는 손실 지연에 효과가 있다고 할 수 있을 것이다.

Keywords

References

  1. National Institutes of Health Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. 2001. Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785-795. https://doi.org/10.1001/jama.285.6.785
  2. Jennings LA, Auerbach AD, Maselli J, Pekow PS, Lindenauer PK, Lee SJ. 2010. Missed opportunities for osteoporosis treatment in patients hospitalized for hip fracture. J Am Geriatr Soc 58: 650-657. https://doi.org/10.1111/j.1532-5415.2010.02769.x
  3. Burge R, Dawson-Hughes B, Solomon DH, Solomon DH, Wong JB, King A, Tosteson A. 2007. Incidence and economic burden of osteoporosis-related fractures in the United States. J Bone Miner Res 22: 465-475. https://doi.org/10.1359/jbmr.061113
  4. Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA. 2008. The laboratory rat as an animal model for osteoporosis research. Comp Med 58: 424-430.
  5. Kaveh K, Ibrahim R, AbuBakar MZ, Ibrahim TA. 2010. Osteoporosis induction in animal model. Am J Anim Vet Sci 5: 139-145. https://doi.org/10.3844/ajavsp.2010.139.145
  6. Zajickova K, Zofkova I. 2003. Osteoporosis: genetic analysis of multifactorial disease. Endoc Regul 37: 31-44.
  7. Berry SD, Kiel DP, Donaldson MG, Cummings SR, Kanis JA, Johansson H, Samelson EJ. 2010. Application of the national osteoporosis foundation guidelines to postmenopausal women and men: the Framingham osteoporosis study. Osteoporos Int 21: 53-60. https://doi.org/10.1007/s00198-009-1127-3
  8. Rubin KH, Abrahamsen B, Hermann AP, Bech M, Gram J, Brixen K. 2011. Prevalence of risk factors for fractures and use of DXA scanning in Danish women. A regional population-based study. Osteoporos Int 22: 1401-1409. https://doi.org/10.1007/s00198-010-1348-5
  9. Blake GM, Fogelman I. 2007. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J 83: 509-517. https://doi.org/10.1136/pgmj.2007.057505
  10. Lin Q, Huang YM, Xiao BX, Ren GF. 2005. Effects of resveratrol on bone mineral density in ovarectomized rats. Int J Biomed Sci 1: 76-81.
  11. Jagtap VR, Ganu JV, Nagane NS. 2011. BMD and serum intact osteocalcin in postmenopausal osteoporosis women. Indan J Clin Biochem 26: 70-73. https://doi.org/10.1007/s12291-010-0074-2
  12. Francisco JI, Yu Y, Oliver RA, Walsh WR. 2011. Relationship between age, skeletal site, and time post-ovariectomy on bone mineral and trabecular microarchitecture in rats. J Orthop Res 29: 189-196. https://doi.org/10.1002/jor.21217
  13. Omi N, Ezawa I. 1995. The effect of ovariectomy on bone metabolism in rats. Bone 17: 163-168.
  14. Ito M, Nishida A, Nakamura T, Uetani M, Hayashi K. 2002. Differences of three-dimensional trabecular microstructure in osteopenic rat models caused by ovariectomy and neurectomy. Bone 30: 594-598. https://doi.org/10.1016/S8756-3282(02)00684-1
  15. Melhus G, Solberg LB, Dimmen S, Madsen JE, Nordsletten L, Reinholt FP. 2007. Experimental osteoporosis induced by ovariectomy and vitamin D deficiency does not markedly affect fracture healing in rat. Acta Orthop 78: 393-403. https://doi.org/10.1080/17453670710013988
  16. Pines A, Fisman EZ, Levo Y, Drory Y, Ben-Ari E, Motro M, Ayalon D. 1993. Menopause-induced changes in left ventricular wall thickness. Am J Cardiol 72: 240-241. https://doi.org/10.1016/0002-9149(93)90171-8
  17. Proudler AJ, Ahmed AI, Crook D, Fogelman I, Rymer JM, Stevenson JC. 1995. Hormone replacement therapy and serum angiotensin-converting-enzyme activity in postmenopausal women. Lancet 346: 89-90. https://doi.org/10.1016/S0140-6736(95)92114-1
  18. Christenson RH. 1997. Biochemical markers of bone metabolism: an overview. Clin Biochem 30: 573-593. https://doi.org/10.1016/S0009-9120(97)00113-6
  19. The co-textbook publishing committee of Korean oriental medicine school. 2010. The herbal medicine. Younglimsa, Seoul, Korea. p 655-656.
  20. Yin J, Tezuka Y, Kouda K, Tran QL, Miyahara T, Chen Y, Kadota S. 2004. Antiosteoporotic activity of the water extract of Dioscorea spongiosa. Biol Pharm Bull 27: 583-586. https://doi.org/10.1248/bpb.27.583
  21. Park SY, Park WT, Park YC, Ju JI, Park SU, Kim JK. 2012. Metabolomics for the quality assessment of Lycium chinense fruits. Biosci Biotechnol Biochem 76: 2188-2194. https://doi.org/10.1271/bbb.120453
  22. Park HJ, Shim HS, Choi WK, Kim KS, Bae H, Shim I. 2011. Neuroprotective effect of Lucium chinense fruit on trimethyltin- induced learning and memory deficits in the rats. Exp Neurobiol 20: 137-143. https://doi.org/10.5607/en.2011.20.3.137
  23. Koo YM. 2008. Effect of Lycii fructus on the ovariectomized osteoporosis of rat. MS Thesis. Kyung Hee University, Seoul, Korea.
  24. Salville PD. 1969. Changes in skeletal mass and fragility with castration in the rat; a model of osteoporosis. J Am Geriatr Soc 17: 155-166. https://doi.org/10.1111/j.1532-5415.1969.tb03169.x
  25. Mobasseri S, Liebson PR, Klein LW. 2004. Hormone therapy and selective estrogen receptor modulators for prevention of coronary heart disease in postmenopausal women estrogen replacement from the cardiologist's perspective. Cardiol Rev 12: 287-298. https://doi.org/10.1097/01.crd.0000131189.50041.d1
  26. Kristensen K, Pedersen SB, Vestergaard P, Mosekilde L, Richelsen B. 1999. Hormone replacement therapy affects body composition and leptin differently in obese and nonobese postmenopausal women. J Endocrinol 163: 55-62. https://doi.org/10.1677/joe.0.1630055
  27. Lin SE, Huang JP, Wu LZ, Wu T, Cui L. 2013. Prevention of osteopenia and dyslipidemia in rats after ovariectomy with combined aspirin and low-dose diethylstilbestrol. Biomed Environ Sci 26: 249-257.
  28. Jayachandran M, Miller VM. 2002. Ovariectomy upregulates expression of estrogen receptors, NOS, and HSPs in porcine platelets. Am J Physiol Heart Circ Physiol 283:220-226. https://doi.org/10.1152/ajpheart.00950.2001
  29. Villafan-Bernal JR, Sanchez-Enriquez S, Munoz-Valle JF. 2011. Molecular modulation of osteocalcin and its relevance in diabetes (review). Int J Mol Med 28: 283-293.
  30. Glowacki J, Lian JB. 1987. Impaired recruitment and differentiation of osteoclast progenitors by osteocalcin-deplete bone implants. Cell Differ 21: 247-254. https://doi.org/10.1016/0045-6039(87)90479-9
  31. Garcia-Perez MA, Noguera I, Hermenegildo C, Martinez- Romero A, Tarin JJ, Cano A. 2006. Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice. Hum Reprod 21: 880-887.
  32. Hayashi T, Yamada K, Esaki T, Kuzuya M, Satake S, Ishikawa T, Hidaka H, Iguchi A. 1995. Estrogen increases endothelial nitric oxide by a receptor-mediated system. Biochem Biophys Res Commun 214: 847-855. https://doi.org/10.1006/bbrc.1995.2364
  33. Hishikawa K, Nakaki T, Marumo T, Suzuki H, Kato R, Saruta T. 1995. Up-regulation of nitric oxide synthase by estradiol in human aortic endothelial cells. FEBS Lett 360:291-293. https://doi.org/10.1016/0014-5793(95)00124-R
  34. MacRitchie AN, Jun SS, Chen Z, German Z, Yuhanna IS, Sherman TS, Shaul PW. 1997. Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary artery endothelium. Circ Res 81: 355-362. https://doi.org/10.1161/01.RES.81.3.355
  35. Mendelsohn ME, Karas RH. 1999. The protective effects of estrogen on the cardiovascular system. N Engl J Med 340: 1801-1811. https://doi.org/10.1056/NEJM199906103402306

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