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Trigonella Goenum-Graecum Seed Extract Alleviates Menopausal Symptoms and Osteoporosis in Ovariectomized Rats

호로파(葫蘆巴) 종자 추출물이 난소 절제술을 받은 쥐에서 갱년기 증상 및 골다공증에 미치는 영향

  • Min Ju Kim (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Mi-Rae Shin (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Hak Joo Choi (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Seong-Soo Roh (Department of Herbology, College of Korean Medicine, Daegu Haany University)
  • 김민주 (대구한의대학교 한의학과 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의학과 본초약리학교실) ;
  • 최학주 (대구한의대학교 한의학과 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의학과 본초약리학교실)
  • Received : 2024.04.18
  • Accepted : 2024.05.25
  • Published : 2024.05.30

Abstract

Objectives : We proposed the hypothesis that administering Trigonella foenum-graecum seed extract (TSE) could alleviate menopausal symptoms and osteoporosis resulting from estrogen deficiency. Methods : Ovariectomized (OVX) rats were administered TSE at doses of 300 or 600 mg/kg body weight for 8 weeks, followed by measurement of serum lipid profile and serum bone markers using ELISA kits. Additionally, analysis of related genes in the femur and uterus was performed using Western blot and real-time PCR. Additionally, micro-CT analysis was performed to investigate the protective effect of TSE against bone loss due to oophorectomy. Results : The administration of TSE led to significant reductions in triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and glucose levels in the serum of OVX rats. Furthermore, TSE increased estradiol levels in the serum and notably improved the levels of biochemical markers associated with bone metabolism. Additionally, TSE exerted significant regulatory effects on the mRNA levels of alkaline phosphatase (ALP) and receptor activator of nuclear factor kappa-B ligand (RANKL)-genes closely associated with bone metabolism in the femur. TSE also demonstrated pronounced effects on uterine tissue, with improvements observed in gene expression related to estrogen receptors. Conclusion : Our findings confirm the efficacy of TSE in ameliorating menopause symptoms by modulating elements associated with both bone and lipid metabolism in the serum, uterine tissue, and femur of OVX rats. The present findings suggest that TSE may offer potential therapeutic effects for symptoms related to menopause and osteoporosis in females.

Keywords

Acknowledgement

본 성과물은 2024년도 정부(과학기술정보통신부)의 재원으로 한국연구재단(No. 2018R1A5A2025272)과 주영엔에스(주)의 지원에 의해 수행되었습니다.

References

  1. Koebele SV, Bimonte-Nelson HA. Modeling menopause: The utility of rodents in translational behavioral endocrinology research. Maturitas. 2016;87:5-17. doi: 10.1016/j.maturitas.2016.01.015.
  2. Seo TS, Jang EJ, Kim JJ, Kim HS, Koo JS. Evaluation of Efficacy for Menopausal Syndrome with Natural Dyed Apparel. Kor. J. Herbol. 2006;21(3):97-102. doi: 10.6116/kjh.2017.32.6.31.
  3. Hybholt M. Psychological and social health outcomes of physical activity around menopause: A scoping review of research. Maturitas. 2022;164:88-97. doi: 10.1016/j.maturitas.2022.07.014.
  4. Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr Opin Nephrol Hypertens. 2011;20(2):133-8. doi: 10.1097/MNH.0b013e3283431921.
  5. Lee JH, Lee S, Nguyen QN, Phung HM, Shin MS, Kim JY, Choi H, Shim SH, Kang KS. Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats. Biomolecules. 2021;11(7): 1033-45. doi: 10.3390/biom11071033.
  6. Kang EY, Kim HK, Jung JY, Kim JH, Woo TK, Choi JI, Kim JH, Ahn C, Lee HG, Go GW. Combined Extract of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi Improved Hot Flashes and Depression in an Ovariectomized Rat Model of Menopause. Foods. 2021;10(1):180-92. doi: 10.3390/foods10010180.
  7. Roepke TA, Ronnekleiv OK, Kelly MJ. Physiological consequences of membrane-initiated estrogen signaling in the brain. Front Biosci (Landmark Ed). 2011;16(4):1560-73. doi: 10.2741/3805.
  8. Hua H, Zhang H, Kong Q, Jiang Y. Mechanisms for estrogen receptor expression in human cancer. Exp Hematol Oncol. 2018;7:24-34. doi: 10.1186/s40164-018-0116-7.
  9. Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332(24):1589-93. doi: 10.1056/NEJM199506153322401.
  10. Flores VA, Pal L, Manson JE. Hormone Therapy in Menopause: Concepts, Controversies, and Approach to Treatment. Endocr Rev. 2021;42(6):720-52. doi: 10.1210/endrev/bnab011.
  11. Hashemzadeh M, Haseefa F, Peyton L, Park S, Movahed MR. The effects of estrogen and hormone replacement therapy on platelet activity: a review. Am J Blood Res. 2022;12(1):33-42. PMID: 35291255.
  12. Aswar U, Bodhankar SL, Mohan V, Thakurdesai PA. Effect of furostanol glycosides from Trigonella foenum-graecum on the reproductive system of male albino rats. Phytother Res. 2010;24(10): 1482-8. doi: 10.1002/ptr.3129.
  13. Seo BI. A Efficacy of Trigonellae Semen On Treatment of Osteporosis In Ovariectomized Rats. Kor. J. Herbology. 2006;21(3):97-102.
  14. Kadaikunnan S, Rejiniemon TS, Alharbi NS, Khaled JM, Agastian P. Identification and quantification of phe-nolic compounds from Trigonella foenum graecum L and its in-vitro antioxidant, anticancer and antimicrobial activities. Fresenius Environ Bull. 2015;24(8A):2643-49.
  15. Lohvina H, Sandor M, Wink M. Effect of Ethanol Solvents on Total Phenolic Content and Antioxidant Properties of Seed Extracts of Fenugreek (Trigonella foenum-graecum L.) varieties and determination of phenolic Composition by HPLC-ESI-MS. 2022; 14(1):7-27. doi:10.3390/d14010007.
  16. Kim H, Cha K, Kim D, Kim H, Koo N, Oh SH. Ameliorating effect of Trigonella foenum-graecum seed extract on andropause symptoms via increased testosterone. J Korean Soc Food Sci Nutr. 2019; 48(2):161-9. doi:10.3746/jkfn.2019.48.2.161.
  17. Deshpande P, Mohan V, Ingavale D, Mane J, Pore M, Thakurdesai PhD P. Preclinical Safety Assessment of Furostanol Glycoside-Based Standardized Fenugreek Seed Extract in Laboratory Rats. J Diet Suppl. 2017;14(5):521-41. doi: 10.1080/19390211.2016.1272659.
  18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972:18(6):499-502. PMID: 4337382. https://doi.org/10.1093/clinchem/18.6.499
  19. Lillie RD, Pizzolato P, Donaldson PT. Nuclear stains with soluble metachrome metal mordant dye lakes. The effect of chemical endgroup blocking reactions and the artificial introduction of acid groups into tissues. Histochemistry. 1976;49(1): 23-35. doi: 10.1007/BF00490123.
  20. Komatsu S. Extraction of nucelar proteins. Methods Mol Biol. 2007;355:73-7. doi: 10.1385/1-59745-227-0:73.
  21. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8. doi: 10.1006/meth.2001.1262.
  22. Lee S, Jung DH, Park M, Yeon SW, Jung SH, Yun SI, Park HO, Yoo W. The Effect of Lactobacillus gasseri BNR17 on Postmenopausal Symptoms in Ovariectomized Rats. J Microbiol Biotechnol. 2021; 31(9):1281-7. doi: 10.4014/jmb.2105.05032.
  23. Kim MR, Yang CH, Seo BI. Effects of Safflower Seeds on Bone Mineral Density in Ovariectomy - Induced Postmenopausal Osteoporotic Rats. Kor. J. Herbol. 1998;13(2):37-43.
  24. Lee GH, Hoang TH, Lee HY, Lim YJ, Kim JH, Jung SJ, Chae SW, Rashid MMU, Chae HJ, Yoon SJ. Ramie leaf Extract Alleviates Bone Loss in Ovariectomized Rats-The Involvement of ROS and Its Associated Signalings. Nutrients. 2023;15(3): 745-58. doi: 10.3390/nu15030745.
  25. Katsuta O, Hiratsuka H, Matsumoto J, Tsuchitani M, Umemura T, Marumo F. Ovariectomy enhances cadmium-induced nephrotoxicity and hepatotoxicity in rats. Toxicol Appl Pharmacol. 1993;119(2): 267-74. doi: 10.1006/taap.1993.1068.
  26. Gouda HN, Sagoo GS, Harding AH, Yates J, Sandhu MS, Higgins JP. The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am J Epidemiol. 2010;171(6):645-55. doi: 10.1093/aje/kwp450.
  27. Mukaiyama K, Kamimura M, Uchiyama S, Ikegami S, Nakamura Y, Kato H. Elevation of serum alkaline phosphatase (ALP) level in postmenopausal women is caused by high bone turnover. Aging Clin Exp Res. 2015;27(4):413-8. doi: 10.1007/s40520-014-0296-x.
  28. Ji MX, Yu Q. Primary osteoporosis in postmenopausal women. Chronic Dis Transl Med. 2015;1(1):9-13. doi: 10.1016/j.cdtm.2015.02.006.
  29. Houillier P, Froissart M, Maruani G, Blanchard A. What serum calcium can tell us and what it can't. Nephrol Dial Transplant. 2006;21(1):29-32. doi: 10.1093/ndt/gfi268.
  30. Shih HY, Lu JH, Xiong AH, Tse JM, Wong BS. Topical application of the plant extract SDTL-E in ovariectomized rats: A potential new approach for treating osteoporosis. Front Med (Lausanne). 2022;9:988235. doi: 10.3389/fmed.2022.988235.
  31. Ito M. Recent progress in bone imaging for osteoporosis research. J Bone Miner Metab. 2011; 29(2):131-40. doi: 10.1007/s00774-010-0258-0.
  32. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010; 25(7):1468-86. doi: 10.1002/jbmr.141.
  33. Parkinson IH, Fazzalari NL. Interrelationships between structural parameters of cancellous bone reveal accelerated structural change at low bone volume. J Bone Miner Res. 2003;18(12):2200-5. doi: 10.1359/jbmr.2003.18.12.2200.
  34. Park SB, Lee YJ, Chung CK. Bone mineral density changes after ovariectomy in rats as an osteopenic model : stepwise description of double dorso-lateral approach. J Korean Neurosurg Soc. 2010;48(4): 309-12. doi: 10.3340/jkns.2010.48.4.309.
  35. Zingue S, Michel T, Nde CBM, Njuh AN, Cisilotto J, Ndinteh DT, Clyne C, Fernandez X, CreczynskiPasa TB, Njamen D. Estrogen-like and tissueselective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study. BMC Complement Altern Med. 2017;17(1): 383-95. doi: 10.1186/s12906-017-1895-9.
  36. Sun W, Sun Y, Zhu M, Wang Z, Zhang H, Xin Y, Jiang G, Guo X, Zhang Z, Liu Y. The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients. Oncol Rep. 2014;31(3):1466-72. doi: 10.1245/s10434-011-1638-y.
  37. Kurki P, Vanderlaan M, Dolbeare F, Gray J, Tan EM. Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. Exp Cell Res. 1986;166(1):209-19. doi: 10.1016/0014-4827(86)90520-3.