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Calcium Bioavailability and Antiosteoporotic Effects of Cheonggukjang Containing High Poly-Gamma Glutamate Contents

고함량 폴리감마글루탐산(PGA) 청국장에 대한 칼슘 생체이용률 및 골다공증에 미치는 영향

  • Lee, Mu-Jin (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Jung, Ho-Kyung (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Sim, Mi-Ok (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Jang, Ji-Hun (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Kim, Tae-Mook (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Lee, Hyun-Joo (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Lee, Ki-Ho (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • An, Byeong-Kwan (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Cho, Jung-Hee (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Jang, Min-Cheol (Heanam Natural Farming Association Corporation) ;
  • Yong, Ju-Hyun (Heanam Natural Farming Association Corporation) ;
  • Kim, Jong-Choon (College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University) ;
  • Cho, Hyun-Woo (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine)
  • 이무진 (한약진흥재단 한약자원본부) ;
  • 정호경 (한약진흥재단 한약자원본부) ;
  • 심미옥 (한약진흥재단 한약자원본부) ;
  • 장지훈 (한약진흥재단 한약자원본부) ;
  • 김태묵 (한약진흥재단 한약자원본부) ;
  • 이현주 (한약진흥재단 한약자원본부) ;
  • 이기호 (한약진흥재단 한약자원본부) ;
  • 안병관 (한약진흥재단 한약자원본부) ;
  • 조정희 (한약진흥재단 한약자원본부) ;
  • 장민철 (해남자연농업영농조합법인) ;
  • 용주현 (해남자연농업영농조합법인) ;
  • 김종춘 (전남대학교 수의과대학 BK21) ;
  • 조현우 (한약진흥재단 한약자원본부)
  • Received : 2016.07.06
  • Accepted : 2016.08.11
  • Published : 2016.11.30

Abstract

Various types of fermented soybean foods are consumed in various Asian countries, including China, Indonesia, Japan, Korea, and Vietnam. Cheonggukjang is a Korean whole soybean paste fermented by Bacillus subtilis and regarded as a healthy food. The objective of this study was to investigate the Ca-bioavailability and anti-osteoporotic effects of cheonggukjang (CGJ) containing high poly-gamma glutamate (PGA) contents in an animal model. Blood samples were collected from the jugular vein at 0, 0.5, 1, 2, 3, 4, and 5 h after a single oral dose in male rats. Ca-bioavailability in CGJ containing high PGA contents was approximately 3~5 times higher than that of natural CGJ. Female rats were either sham-operated (sham; n=5) or surgically ovariectomized (OVX; five animals per group) and then administered to OVX control, raloxifene hydrochloride (RLX) 1 mg/kg/d, or CGJ containing high contents of PGA (20 and 200 mg/kg/d) for 12 weeks. Serum osteocalcin concentration was significantly lower in the CGJ 200 mg/kg/d group compared with the OVX control group. Serum progesterone concentration was significantly higher in the CGJ 200 mg/kg/d group compared with the OVX control group. Reduction grade of the trabecular bone decreased in the RLX 1 and CGJ 200 mg/kg/d group compared with that of the OVX control group. In conclusion, CGJ 200 mg/kg/d may have inhibitory effects on osteoporosis in OVX rats, and Ca-bioavailability was improved in CGJ containing high PGA contents.

본 연구는 칼슘 생체이용률 시험에 수컷 랫드를 이용하여 고함량 폴리감마글루탐산 청국장이 기존 청국장보다 칼슘의 생체이용률을 증가시키는지 알아보고자 실시하였다. 고함량 폴리감마글루탐산(PGA) 청국장 및 기존 청국장을 투여하고 0.5, 1, 2, 3, 4, 5시간에 채혈하여 칼슘 함량을 측정한 결과, 고함량 PGA 청국장이 기존 청국장보다 투여 후 3~5시간에 칼슘 흡수율이 증가할 것으로 생각한다. 골다공증 시험에 난소를 적출하여 폐경을 유도한 후 PGA 함유량이 증가한 청국장을 12주간 경구투여 하여 골다공증에 미치는 효과를 연구하고자 하였다. 혈청 검사에서 오스테오칼신은 청국장 200 mg/kg 투여군에서 OVX 대조군보다 유의성 있는 감소가 관찰되었고, 프로게스테론은 청국장 200 mg/kg 투여군에서는 OVX 대조군보다 유의성 있는 증가가 관찰되어 청국장이 골다공증 개선에 효과가 있는 것으로 생각한다. 간장 조직액의 지질과산화물은 OVX 대조군보다 대조약 및 청국장 투여군에서 모두 감소 경향이 관찰되어 청국장 투여로 지질과산화물 생성을 감소시키는 것으로 기대된다. 대퇴골에 대한 조직병리학적 검사에서 대퇴골 원위부 골간단의 해면골 감소가 대조약은 OVX 대조군보다 유의성 있는 감소가 관찰되었으며, 청국장 200 mg/kg 투여군에서도 감소가 관찰되어 청국장이 해면골 감소를 억제시키는 것으로 생각한다. 이상의 결과는 고함량 PGA 청국장이 기존 청국장보다 투여 후 3~5시간에 칼슘 흡수율을 증가시킬 것으로 생각하고, 난소적출 후에 일어나는 골격 대사의 이상에도 청국장이 골 교체율 억제, 호르몬 변화, 항산화 및 해면골 감소 억제 등 유익하게 나타남으로써 임상상 폐경기에 나타나는 골다공증을 어느 정도 예방시킬 수 있음을 시사하며, 폐경 후 여성의 골대사에 유익한 효과를 줄 것으로 생각한다.

Keywords

References

  1. Walsh CA, Birch MA, Fraser WD, Ginty AF, Gallagher JA. 2000. Cytokine expression by cultured osteoblasts from patients with osteoporotic fractures. Int J Exp Path 81: 159-163.
  2. Park HM. 2010. Current use of drugs for osteoporosis in Korea. Korean J Obstet Gynecol 53: 152-159. https://doi.org/10.5468/kjog.2010.53.2.152
  3. Lee JW, Kim H, Jhee O, Won H, Yu Y, Lee M, Kim T, Om A, Kang J. 2005. Effects of alternative medicine extract on bone mineral density, bone strength and biochemical markers of bone metabolism in ovariectomized rats. Korean J Food Nutr 18: 72-80.
  4. Kim YM, Kim JH, Cho DS. 2015. Gender difference in osteoporosis prevalence, awareness and treatment: based on the Korea national health and nutrition examination survey 2008-2011. J Korean Acad Nurs 45: 293-305. https://doi.org/10.4040/jkan.2015.45.2.293
  5. Chung HY. 2008. Osteoporosis diagnosis and treatment 2007. J Korean Endocr Soc 23: 76-108. https://doi.org/10.3803/jkes.2008.23.2.76
  6. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. 1994. The diagnosis of osteoporosis. J Bone Min Res 9: 1137-1141.
  7. Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Hunter DJ, Hennekens CH, Speizer FE. 1997. Postmenopausal hormone therapy and mortality. N Engl J Med 336: 1769-1775. https://doi.org/10.1056/NEJM199706193362501
  8. Choi HJ. 2013. Treatment for osteoporosis: focusing on bisphosphonate therapy. Korean J Fam Pract 3: 16-24.
  9. Kang MJ, Cho JY, Shim BH, Kim DK, Lee J. 2009. Bioavailability enhancing activities of natural compounds from medicinal plants. J Med Plant Res 13: 1204-1211.
  10. Lee JO, Ha SD, Kim AJ, Yuh CS, Bang IS, Park SH. 2005. Industrial application and physiological functions of Chongkukjang. Food Science and Industry 38(2): 69-78.
  11. Kang SA, Jang KH, Cho Y, Hong K, Suh JH, Choue R. 2003. Effects of artificial stomach fluid and digestive enzymes on the aglycone isoflavone contents of soybean and black bean (Rhynchosia molubillis: Yak-Kong). Korean J Nutr 36: 32-39.
  12. Tanimoto H, Mori M, Motoki M, Torii K, Kadowaki M, Noguchi T. 2001. Natto mucilage containing poly-${\gamma}$-glutamic acid increases soluble calcium in the rat small intestine. Biosci Biotechnol Biochem 65: 516-521. https://doi.org/10.1271/bbb.65.516
  13. Lee MS, Kang JI, Kim HS. 2006. Effect of ${\gamma}$-PGA(poly-${\gamma}$- glutamic acid) supplement on calcium absorption and bone metabolism in rats. J Korean Soc Food Sci Nutr 35: 255-261. https://doi.org/10.3746/jkfn.2006.35.3.255
  14. Louie DS. 1996. Calcium and phosphorus in health and disease: Intestinal bioavailability and absorption of calcium. CRC Press, Boca Raton, FL, USA. p 45.
  15. Booth SL, Suttie JW. 1998. Dietary intake and adequacy of vitamin K. J Nutr 128: 758-788. https://doi.org/10.1093/jn/128.4.758
  16. Akedo Y, Hosoi T, Inoue S, Ikegami A, Mizuno Y, Kaneki M, Nakamura T, Ouchi Y, Orimo H. 1992. Vitamin $K_2$ modulates proliferation and function of osteoblastic cells in vitro. Biochem Biophys Res Commun 187: 814-820. https://doi.org/10.1016/0006-291X(92)91269-V
  17. Lee KH, Ryu SH, Lee YS, Kim YM, Moon GS. 2005. Changes of antioxidative activity and related compounds on the Chungkukjang preparation by adding drained boiling water. Korean J Food Cook Sci 21: 163-170.
  18. Choi YB, Sohn HS. 1998. Isoflavone content in Korean fermented and unfermented soybean foods. Korean J Food Sci Technol 30: 745-750.
  19. Chung WY, Kim SK, Son JY. 2008. Isoflavones contents and physiological activities of soybeans fermented with Aspergillus oryzae or Bacillus natto. J Korean Soc Food Sci Nutr 37: 141-147. https://doi.org/10.3746/jkfn.2008.37.2.141
  20. Somekawa Y, Chiguchi M, Ishibashi T, Aso T. 2001. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 97: 109-115.
  21. Morabito N, Crisafulli A, Vergara C, Gaudio A, Lasco A, Frisina N, D'Anna R, Corrado F, Pizzoleo MA, Cincotta M, Altavilla D, Ientile R, Squadrito F. 2002. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo- controlled study. J Bone Miner Res 17: 1904-1912. https://doi.org/10.1359/jbmr.2002.17.10.1904
  22. Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, Watanabe S. 2007. Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 85: 1148-1156. https://doi.org/10.1093/ajcn/85.4.1148
  23. Akesson K, Lau KH, Baylink DJ. 1997. Rationale for active vitamin D analog therapy in senile osteoporosis. Calcif Tissue Int 60: 100-105. https://doi.org/10.1007/s002239900195
  24. Bang BH, Rhee MS, Kim KP, Yi DH. 2012. Influences of culture medium components on the production poly(${\gamma}$-glutamic acid) by Bacillus subtilis GS-2 isolated Chungkookjang. Korean J Food Nutr 25: 677-684. https://doi.org/10.9799/ksfan.2012.25.3.677
  25. Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, Cullinan GJ, Bendele R, Kauffman RF, Bensch WR, Frolik CA, Termine JD, Bryant HU. 1994. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 93: 63-69. https://doi.org/10.1172/JCI116985
  26. Lee KH, Sim MO, Song YS, Jung HK, Jang JH, Kim MS, Kim TM, Lee HE, An BK, Jung WS. 2016. Effects of polygamma glutamate contents Cheonggukjang on osteoblast differentiation. J Korean Soc Food Sci Nutr 45: 664-670. https://doi.org/10.3746/jkfn.2016.45.5.664
  27. Allen LH. 1982. Calcium bioavailability and absorption: a review. Am J Clin Nutr 35: 783-808. https://doi.org/10.1093/ajcn/35.4.783
  28. Pansu D, Bellaton C, Bronner F. 1981. Effect of Ca intake on saturable and nonsaturable components of duodenal Ca transport. Am J Physiol 240: G32-G37.
  29. Bronner F. 1992. Current concepts of calcium absorption: an overview. J Nutr 122: 641-643. https://doi.org/10.1093/jn/122.suppl_3.641
  30. Park C, Chol YH, Shin HJ, Poo HY, Song JJ, Kim CJ, Sung MH. 2005. Effect of high-molecular-weight poly-${\gamma}$-glutamic acid from Bacillus subtilis (chungkookjang) on Ca solubility and intestinal absorption. J Microbiol Biotechnol 15: 855-858.
  31. Han KO. 2005. Molecular pathophysiology of postmenopausal osteoporosis. J Korean Soc Menopause 11: 175-177. https://doi.org/10.1258/136218005775544327
  32. Li M, Wronski TJ. 1995. Response of femoral neck to estrogen depletion and parathyroid hormone in aged rats. J Bone Miner Res 16: 551-557.
  33. Johnell O, Oden A, De Laet C, Garnero P, Delmas PD, Kanis JA. 2002. Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int 13: 523-526. https://doi.org/10.1007/s001980200068
  34. Abadjieva DK, Kang SK. 1996. Effects of Cervi Cornu aquaacupuncture on lipid metabolism and osteoporosis in ovariectomized rats. J Korean Orient Med 17: 168-177.
  35. Kim SJ. 2003. Study on the relationship between osteoporosis- cause factor and bone mineral density, biochemical marker. MS Thesis. Pukyong National University, Busan, Korea. p 28-29.
  36. Liu G, Peacock M. 1998. Age-related changes in serum undercarboxylated osteocalcin and its relationships with bone density, bone quality, and hip fracture. Calcif Tissue Int 62: 286-289. https://doi.org/10.1007/s002239900432
  37. McDonald LE, Pineda MH. 1989. Veterinary endocrinology and reproduction. 4th ed. Lea and Febiger Philadelphia, PA, USA. p 303-354.
  38. Heersche JN, Bellows CG, Ishida Y. 1998. The decrease in bone mass associated with aging and menopause. J Prosthet Dent 79: 14-16. https://doi.org/10.1016/S0022-3913(98)70187-8
  39. Lee O. 2004. Effects of supplementation of Puerariae radix ethanol extract on the antioxidative defense system in rats. Korean J Nutr 37: 872-880.
  40. Thurman RG, Bradford BU, Iimuro Y, Knecht KT, Connor HD, Adachi Y, Wall C, Arteel GE, Raleigh JA, Forman DT, Mason RP. 1977. Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: studies in female and male rats. J Nutr 127: 903S-906S.
  41. Morel DW, Chisolm GM. 1989. Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity. J Lipid Res 30: 1827-1834.
  42. Kimmel DB. 1996. Animal models for in vivo experimentation in osteoporosis research. Osteoporosis Academic Press, San Diego, CA, USA. p 671-690.