Antipostmenopausal effects of Stauntonia hexaphylla and Vaccinium bracteatum fruit combination in estrogen-deficient rats

  • Gyuok Lee Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Jawon Shin
  • Ara Jo Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Sojeong Lm Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Mi-Ri Kim Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Yunhee Shoi Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Hyojeong Yun Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Donghyuck Bae Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Jaeyong Kim Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
  • Chul-yung Choi Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources Research (JINR), Jeollanamdo, Republic of Korea
Keywords: estrogen, hot flushes, menopause, osteoporosis, ovariectomy

Abstract

Background: Climacterium is a series of physical and mental symptoms occurring in women and men due to decreased levels of sex hormones. Women lose the ability to become pregnant due to decreased ovarian estrogen production; the initial symptom being hot flushes. In addition, urogenital atrophy, sexual dysfunction, mood changes, and osteoporosis occur. Extracts of Stauntonia hexaphylla (SH) and Vaccinium bracteatum (VB) fruits, with a wide range of biological activities, are widely used in traditional herbal medicine.

Objective: The purpose of this study was to investigate the mitigation of menopausal symptoms, such as hot flushes and postmenopausal osteoporosis after combinatorial treatment with SH and VB (SHVB) of ovariectomized (OVX) rats.

Design: We measured the bone regenerative effect of SHVB on receptor activator of nuclear factor-κB (NF- κB) ligand-induced osteoclast differentiation in vitro and on ovariectomy-induced osteoporosis in vivo. We investigated the effect of SHVB in a rat model of menopausal hot flushes, in which the tail skin temperature increases following ovariectomy-induced rapid decline in estrogen levels.

Results: SHVB inhibited osteoclast formation and tartrate-resistant acid phosphatase activity in primary mouse bone marrow-derived cells. In an estrogen deficiency-induced rat model, measurement of serum bone turnover factors showed that treatment with SHVB lowered the increased bone turnover. Additionally, SHVB decreased OVX-induced bone loss of the total femur. SHVB inhibited osteoclast differentiation, prevented bone mass reduction, and improved trabecular bone structure and biochemical markers in OVX-induced osteoporosis. In addition, administration of SHVB significantly ameliorated the changes in skin temperature in OVX rats.

Conclusion: SHVB improved the symptoms of menopause. These results provide the foundation for developing SHVB as a natural substance to replace hormones in the future.

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References


  1. Nejat EJ, Chervenak JL. The continuum of ovarian aging and clinicopathologies associated with the menopausal transition. Maturitas 2010; 66: 187–90. doi: 10.1016/j.maturitas.2010.02.017

  2. Newton KM, Buist DS, Keenan NL, Anderson LA, LaCroix AZ. Use of alternative therapies for menopause symptoms: results of a population-based survey. Obstet Gynecol 2002; 100: 18–25. doi: 10.1016/s0029-7844(02)02005-7

  3. Bonnick SL, Harris ST, Kendler DL, Mcclung MR, Silverman SL. Management of osteoporosis in post-menopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010; 17: 25–54. doi: 10.1097/gme.0b013e3181c617e6

  4. Alexander JMI, Fish S, Muller R, Uchiyama T, Gronowicz G, Nahounou M, et al. Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice. J Bone Miner Res 2001; 16(9): 1665–73. doi: 10.1359/jbmr.2001.16.9.1665

  5. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005; 115(12): 3318–25. doi: 10.1172/JCI27071

  6. Takayanagi H. Inflammatory bone destruction and osteoimmunology. J Periodontal Res 2005; 40(4): 287–93. doi: 10.1111/j.1600-0765.2005.00814.x

  7. Papachroni KK, Karatzas DN, Papavassiliou KA, Basdra EK, Papavassiliou AG. Mechanotransduction in osteoblast regulation and bone disease. Trends Mol Med 2009; 15(5): 208–16. doi: 10.1016/j.molmed.2009.03.001

  8. Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation. Bone 2007; 40(2): 250–64. doi: 10.1016/j.bone.2006.09.023

  9. Wada T, Nakashima T, Hiroshi N, Penninger JM. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 2006; 12(1): 17–25. doi: 10.1016/j.molmed.2005.11.007

  10. Jung K, Lein M. Bone turnover markers in serum and urine as diagnostic, prognastic and monitoring biomarkers of bone metastasis. Biochim Biophys Acta 2014; 1846(2): 425–38. doi: 10.1016/j.bbcan.2014.09.001

  11. Ferreira A, Alho I, Casimiro S, Costa L. Bone remodeling markers and bone metastases: from cancer research to clinical implications. BoneKEy Rep 2015; 22(4): 1–9. doi: 10.1038/bonekey.2015.35

  12. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012; 97(4): 1159–68. doi: 10.1210/jc.2011-3362

  13. Freeman EW, Sammel MD, Lin H, Liu Z, Gracia CR. Duration of menopausal hot flushes and associated risk factors. Obstet Gynecol 2011; 117(5): 1095–104. doi: 10.1097/AOG.0b013e318214f0de

  14. Shen W, Stearns V. Treatment strategies for hot flushes. Expert Opin Pharmacother 2009; 10(7): 1133–44. doi: 10.1517/14656560902868217

  15. Freedman RR. Physiology of hot flashes. Am J Hum Biol 2001; 13(4): 453–64. doi: 10.1002/ajhb.1077

  16. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women; principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288(3): 321–33. doi: 10.1001/jama.288.3.321

  17. Carroll DG, Kelley KW. Use of antidepressants for management of hot flashes. Pharmacotherapy 2009; 29(11): 1357–74. doi: 10.1592/phco.29.11.1357

  18. Shin CC, Wu YW, Lin WC. Ameliorative effects of Anoectochilus formosanus extract on osteopenia in ovariectomized rats. J Ethnopharmacol 2001; 77(2–3): 233–8. doi: 10.1016/s0378-8741(01)00302-6

  19. Ahldorg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. N Engl J Med 2003; 349(4): 327–34. doi: 10.1056/NEJMoa022464

  20. Curtis R, Goldhan J, Schwyn R, Regazzoni P, Suhm N. Fixation principles in metaphyseal bone – a patent based review. Osteoporosis Int 2005; 16(2): S54–64. doi: 10.1007/s00198-004-1763-6

  21. Stevenson JC. Justification for the use of HRT in the long-term prevention of osteoporosis. Maturitas 2005; 51(2): 113–26. doi: 10.1016/j.maturitas.2005.01.012

  22. Prelevic GM, Kocjan T, Markou A. Hormone replacement therapy in postmenopausal women. Minerva Endocrinol 2005; 30(1): 27–36. Available from: https://europepmc.org/article/med/15877011 [cited 2016 Dec 20]

  23. Ikuta A, Morikawa A, Kubota K. A saponin from callus tissue of Stauntonia hexaphylla. Phytochemistry 1991; 30(7): 2425–7. doi: 10.1016/0031-9422(91)83672-8

  24. Park YJ, Park YS, Park JO, Kim YM, Jung KJ, Jeo JY, et al. Chemical components and biological activity of Stauntonia hexaphylla. Korean J Plant Res 2009; 22(5): 403–11. Available from: http://db.koreascholar.com/article.aspx?code=258938 [cited 2012 Jan 10]

  25. Wang HB, Mayer R, Rücker G, Yang JJ, Matteson DS. A phenolic glycoside and triterpenoids from Stauntonia hexaphylla. Phytochemistry 1998; 47(3): 467–70. doi: 10.1016/S0031-9422(97)00588-8

  26. Hwang SH, Kwon SH, Kim SB, Lim SS. Inhibitory activities of Stauntonia hexaphylla leaf constituents on rat lens aldose reductase and formation of advanced glycation end products and antioxidant. Biomed Res Int 2017; 2017: 4273257. doi: 10.1155/2017/4273257

  27. Cheon YH, Baek JM, Park SH, Ahn SJ, Lee MS, Oh J. Stauntonia hexaphylla (Lardizabalaceae) leaf methanol extract inhibits osteoclastogenesis and bone resorption activity via proteasome-mediated degradation of c-Fos protein and suppression of NFATc1 expression. BMC Complement Altern Med 2015; 15: 280. doi: 10.1186/s12906-015-0801-6

  28. Kim J, Kim H, Choi H, Jo A, Kang H, Yun H, et al. Anti-inflammatory effects of a Stauntonia hexaphylla fruit extract in lipopolysaccharide-activated RAW-264.7 macrophages and rats by carrageenan-induced hind paw swelling. Nutrients 2018; 10(1): 1–12. doi: 10.3390/nu10010110

  29. Lee G, Kim J, Kang H, Bae D, Choi CY. Antioxidant activities and hepato-protective effects of Stauntonia hexaphylla fruit extract against H2O2-induced oxidative stress and acetaminophen induced toxicity. J Life Sci 2018; 28(6): 708–17. doi: 10.5352/JLS.2018.28.6.708

  30. Wang L, Jiang TY, Zhang H, Yao HY. Study on the extraction of black pigment from Vaccinium bracteatum Thunb. leaves by enzyme and its stability. Sci Technol Food Industry 2008; 29: 224–6. Available from: http://en.cnki.com.cn/Article_en/CJFDTOTAL-SPKJ200810069.htm [cited 2018 Nov 7]

  31. Hu J, Wang J, Li S, Yang B, Gong M, Li X, et al. Phytochemical compositions, antioxidant and antimicrobial activities analysis of extracts from Vaccinium bracteatum Thunb. leaves. J App Bot Food Qual 2016; 89: 150–5. doi: 10.5073/JABFQ.2016.089.018

  32. Wang L, Zhang XT, Zhang HY, Yao HY, Zhang H. Effect of vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice. J Ethnopharmacol 2010; 130(3): 465–9. doi: 10.1016/j.jep.2010.05.031

  33. Wang L, Zhang Y, Xu M, Wang Y, Chenq S, Liebrecht A, et al. Antidiabetic activity of Vaccinium bracteatum Thunb. leaves’ polysaccharide in STZ-induced diabetic mice. Int J Biol Macromol 2013; 61: 317–21. doi: 10.1016/j.ijbiomac.2013.07.028

  34. Zhang J, Chu CJ, Li XL, Yao S, Yan B, Ren HL, et al. Isolation and identification of antioxidant compounds in Vaccinium bracteatum Thunb. by UHPLC-Q-TOF LC/MS and their kidney damage protection. J Funct Foods 2014; 11: 62–70. doi: 10.1016/j.jff.2014.09.005

  35. Wang L, Zhang X, Yao H. The protective effect of Vaccinium bracteatum Thunb. leaves and the extract against light injury of retina. J Xi’an Jiaotong Uni 2006; 27: 284–7. Available from: http://en.cnki.com.cn/Article_en/CJFDTOTAL-XAYX200603022.htm [cited 2017 Apr 12]

  36. Kwon SH, Ma SX, Ko YH, Seo JY, Lee BR, Lee TH, et al. Vaccinium bracteatum Thunb. exerts anti-inflammatory activity by inhibiting NF-kappaB activation in BV-2 microglial cells. Biomol Ther 2016; 24(5): 543–51. doi: 10.4062/biomolther.2015.205

  37. Landa P, Skalova L, Bousova I, Kutil Z, Langhansova L, Lou JD, et al. In vitro antiproliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb. Pak J Pharm Sci 2014; 27(1): 103–6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24374437 [cited 2018 Jun 4]

  38. Oh DR, Kim Y, Choi EJ, Jung MA, Oh KN, Hong JA, et al. Antidepressant-like effects of Vaccinium bracteatum in chronic restraint stress mice: functional actions and mechanism explorations. Am J Chin Med 2018; 46(2): 357–87. doi: 10.1142/S0192415X18500180

  39. Oh DR, Kim Y, Choi EJ, Jo A, Shin J, Kang H, et al. Antidepressant effects of Vaccinium bracteatum via protection against hydrogen peroxide-induced oxidative stress and apoptosis. Am J Chin Med 2018; 4: 1–20. doi: 10.1142/S0192415X18500775

  40. Oh DR, Kim Y, Jo A, Choi EJ, Oh KN, Kim J, et al. Sedative and hypnotic effects of Vaccinium bracteatum Thunb. through the regulation of serotonegic and GABAA-ergic systems: involvement of 5-HT1A receptor agonistic activity. Biomed Pharmacother 2019; 109: 2218–27. doi: 10.1016/j.biopha.2018.10.003

  41. Oh DR, Kim Y, Jo A, Im S, Kim CE, Jung M-A, et al. Antidepressant-like and hypnotic effects of the herbal extract combination of stauntonia hexaphylla and vaccinium bracteatum fruit in mice. J Physiol Pathol Korean Med 2020; 34(2): 88–96. Available from: https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002580821 [cited 2020 Feb 15]

  42. Wolff LPG, Martins MR, Bedone AJ, Monteiro MU. Endometrial evaluation in menopausal women after six months of isoflavones. Rev Assoc Med Bras 2006; 52(6): 419–23. doi: 10.1590/S0104-42302006000600022

  43. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy. JAMA 2002; 288(7): 872–81. doi: 10.1001/jama.288.7.872

  44. Ross FP, Teitelbaum SL. αvβ and macrophage colony-stimulating factor: partnersin osteoclast biology. Immunol Rev 2005; 208: 88–105. doi: 10.1111/j.0105-2896.2005.00331.x

  45. Takayanagi H, Sato K, Takaoka A, Taniguchi T. Interplay between interferon and other cytokine systems in bone metabolism. Immunol Rev 2005; 208: 181–93. doi: 10.1111/j.0105-2896.2005.00337.x

  46. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001; 142(12): 5050–5. doi: 10.1210/endo.142.12.8536

  47. Hohenhaus MH, McGarry KA, Col NF. Hormone therapy for the prevention of bone loss in menopausal women with osteopenia: is it a viable option? Drugs 2007; 67(16): 2311–21. doi: 10.2165/00003495-200767160-00002

  48. Levine JP. Effective strategies to identify postmenopausal women at risk for osteoporosis. Geriatrics 2007; 62(11): 22–30. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17999567 [cited 2014 Nov 23]

  49. Hoegh-Andersen P, Andersen TL, Lundberg CV, Mo JA, Heegaard A, Delaisse J, et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res Ther 2004; 6(2): R169–80. doi: 10.1186/ar1152

  50. Jee WS, Yao W. Overview: animal models of osteopenia and osteoporosis. J Musculoskel Neuron Interact 2001; 1(3): 193–207. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15758493 [cited 2014 Nov 25]

  51. Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA. The laboratory rat as an animal model for osteoporosis research. Comp. Med 2008; 58(5): 424–30. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19004367 [cited 2015 Jan 9]

  52. Recker R, Masarachia P, Santora A, Howard T, Chavassieux P, Arlot M, et al. Trabecular bone microarchitecture after alendronate treatment of osteoporotic women. Curr. Med Res Opin 2005; 21(2), 185–94. doi: 10.1185/030079904X20259

  53. Huang G, Wu J, Wang S, Wei Y, Chen F, Chen J, et al. Pycnogenol ® treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats. Int J Clin Exp Med 2015; 8(7): 10893–901. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565266 [cited 2017 Sep 14]

  54. Cano A, Dapía S, Noguera I, Pineda B, Hermenegildo C, del Val R, et al. Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice. Osteoporos Int 2008; 19(6): 793–800. doi: 10.1007/s00198-007-0498-6

  55. Shim SK, Lee CJ, Yim NH, Gu MJ, Ma JY. Alpinia officinarum stimulates osteoblast mineralization and inhibits osteoclast differentiation. Am J Chin Med 2016; 44(6): 1255–71. doi: 10.1142/S0192415X16500701

  56. Hlaing TT, Compston J. Biochemical markers of bone turnover-uses and limitations. Ann Clin Biochem 2014; 51(2): 189–202. doi: 10.1177/0004563213515190

  57. Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26(4): 97–122. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16648882 [cited 2016 Nov 19]

  58. Stein KD, Jacobsen PB, Hann DM, Greenberg H, Lyman G. Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer. J Pain Symptom Manage 2000; 19: 436–45. doi: 10.1016/S0885-3924(00)00142-1

  59. Berendsen HH, Weekers AH, Kloosterboer HJ. Effect of tibolone and raloxifene on the tail temperature of oestrogen-deficient rats. Eur J Pharmacol 2001; 419(1): 47–54. doi: 10.1016/s0014-2999(01)00966-9

  60. Opas EE, Rutledge SJ, Vogel RL, Rodan GA, Schmidt A. Rat tail skin temperature regulation by estrogen, phytoestrogen and tamoxifen. Maturitas 2004; 48(4): 463–71. doi: 10.1016/j.maturitas.2003.11.001

  61. Sipe K, Leventhal L, Burroughs K, Cosmi S, Johnston GH, Deecher DC. Serotonin 2a receptors modulate tail-skin temperature in two rodent models of estrogen deficiency-related thermoregulatory dysfunction. Brain Res 2004; 1028(2): 191–202. doi: 10.1016/j.brainres.2004.09.012

  62. Bowe J, Li XF, Kinsey-Jones J, Heyerick A, Brain S, Milligan S, et al. The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. J Endocrinol 2006; 191(20): 399–405. doi: 10.1677/joe.1.06919

Published
2020-10-15
How to Cite
Lee, G., Shin, J., Jo, A., Lm, S., Kim, M.-R., Shoi, Y., Yun, H., Bae, D., Kim, J., & Choi, C.- yung. (2020). Antipostmenopausal effects of <em>Stauntonia hexaphylla</em> and <em>Vaccinium bracteatum</em&gt; fruit combination in estrogen-deficient rats. Food & Nutrition Research, 64. https://doi.org/10.29219/fnr.v64.5233
Section
Original Articles