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Effects of a Mixture of Cynanchi Wilfordii Radix and Humuli Lupuli Flos Extract on Estrogenic Activities and Anti-Osteoclastogenesis

백수오(白首烏)와 비주화(啤酒花) 복합물의 에스트로겐 활성과 파골세포 분화 억제효과

  • Received : 2022.06.14
  • Accepted : 2022.09.25
  • Published : 2022.09.30

Abstract

Objectives : This study aimed to investigate the synergistic effect of combining Cynanchi Wilfordii Radix extract with Humuli Lupuli Flos extract on estrogenic and anti-osteoclastogenic activity. Methods : Estrogenic effect of a mixture of Cynanchi Wilfordii Radix extract and Humuli Lupuli Flos extract (CWHL), Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin (an active ingredient of Cynanchi wilfordii Radix extract) and 8-prenylnaringenin (an active ingredient of Humuli Lupuli Flos extract) were examined by proliferation E-screen assay and expression of estrogen inducible gene, pS2 via Real Time-PCR (RT-PCR) in MCF-7 estrogen responsive cells. And their estrogenic activities were investigated how to modulate Estrogen receptor 𝛽 by binding affinity assay. Inhibitory effect of CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin on RANKL-induced osteoclast differentiation were tested by TRAP (Tartrate-resistant acid phosphatase) staining in osteoclastogenic RAW 264.7 cells. Results : CWHL, Humuli Lupuli Flos extract and 8-prenylnaringenin accelerated the proliferation of MCF-7 and the expression of pS2 in MCF-7. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin bind to estrogen receptor 𝛽. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin inhibited RANKL-induced osteoclastogenesis in osteoclastogenic RAW 264.7. CWHL is more effective for all markers than Cynanchi Wilfordii Radix extract or Humuli Lupuli Flos extract alone. Conclusions : CWHL may a potential therapeutic agent for menopause and osteoporosis as a natural food resource. CWHL as a natural food source has therapeutic potential in cases of menopause and osteoporosis.

Keywords

References

  1. Neugarten BL, Kraines RJ. "Menopausal symptoms" in women of various ages. Psychosom Med. 1965 ; 27 : 266-73. https://doi.org/10.1097/00006842-196505000-00009
  2. Grady D. Management of menopausal symptoms. N Engl J Med. 2006 ; 355 : 2338-47. https://doi.org/10.1056/NEJMcp054015
  3. Cho HS, Kim HG, Ahn S, Yoo GN. A case report of the effects of Jia Wei Si Wu Tang (augmented four-substance decoction) on a menopausal disorder patient. J Korea Instit Orient Med Diagn. 2011 ; 15(2) : 215-222
  4. Du HK. Oriental kidney system internal medicine. Seoul:Sungbosa. 2003 : 1241-50.
  5. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SAA, Howard BV, Johnson KC, Kotchen JM, Ockene J. 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 : 321-33. https://doi.org/10.1001/jama.288.3.321
  6. Lobo RA. Benefits and risks of estrogen replacement therapy. Am J Obstet Gynecol. 1995 ; 173 : 982-9. https://doi.org/10.1016/0002-9378(95)90247-3
  7. Wallach EE, Gambrell Jr RD. The menopause benefits and risks of estrogen - progestogen replacement therapy. Fertil Steril. 1982 ; 37 : 457-74. https://doi.org/10.1016/S0015-0282(16)46149-2
  8. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms : a review of randomized, controlled trials. Ann Intern Med. 2002 ; 137 : 805-13. https://doi.org/10.7326/0003-4819-137-10-200211190-00009
  9. Han KK, Soares Jr JM, Haidar MA, De Lima GR, Baracat EC. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. 2002 ; 99 : 389-94.
  10. Chung MH, Kim GW, Lee BJ, Um KJ. Studies on efficacy of Polygoni multiflori Radix and Cynanchi wilfordi Radix. Kor. J. Pharmacogn. 1991 ; 22(1) : 67.
  11. Kim HJ. Effects of Cynanchum wilfordii extract on serum lipid components and enzyme activities in hyperlipidemic and streptozotocin induced diabetic rats. Korean J. Human. Ecology. 2004 ; 7(2) : 1-11.
  12. Kim HK, Kim YA, Lee AY, Ko BS. Pattern analysis of Cynanchi wilfordii radix and Polygoni multiflori radix. Kor J Pharmacogn. 2003 ; 34(4) : 278-81
  13. Qiu S, Cho JS, Kim JT, Moon JH, Zhou Y, Lee SB, Park HJ, Lee HJ. Caudatin suppresses adipogenesis in 3T3-L1 adipocytes and reduces body weight gain in high-fat diet-fed mice through activation of hedgehog signaling. Phytomedicine. 2021 ; 92 : 153715 https://doi.org/10.1016/j.phymed.2021.153715
  14. Wang LJ, Chen H, Ma YB, Huang XY, Geng CA, Zhang XM, Chen JJ. Design, synthesis and biological evaluation of caudatin analogs as potent hepatitis B virus inhibitors. Med Chem. 2015 ; 11(2) : 165-79. https://doi.org/10.2174/1573406410666140902111326
  15. Zhen X, Choi HS, Kim JH, Kim SL, Liu R, Ko YC, Yun BS, Lee DS. Caudatin isolated from Cynanchumauriculatum inhibits breast cancer stem cell formation via a GR/YAP Signaling. Biomolecules. 2020 18 ; 10(6) : 925. https://doi.org/10.3390/biom10060925
  16. Song J, Ding W, Liu B, Liu D, Xia Z, Zhang L, Cui L, Luo Y, Jia X, Feng L. Anticancer effect of caudatin in diethylnitrosamine-induced hepatocarcinogenesis in rats. Mol Med Rep. 2020 ; 22(2) : 697-706. https://doi.org/10.3892/mmr.2020.11135
  17. 한국한의학연구원. 비주화(啤酒花) [Internet]. 특허청; 2007. Available from: https://doi.org/10.20929/KTKP.MED.0000078189
  18. Cleemput MV, Cattoor K, Bosscher KD, Haegeman G, Keukeleire DD, Heyerick A. Hop (Humulus lupulus)-derived bitter acids as multipotent bioactive compounds. J. Nat. Prod. 2009 ; 72 : 1220-1230. https://doi.org/10.1021/np800740m
  19. Wang J, Li D, Dangott LJ, Wu G. Proteomics and Its Role in Nutrition Research. The Journal of Nutrition. 2006 ; 136(7) : 1862-1867. https://doi.org/10.1093/jn/136.7.1862
  20. Effenberger KE, Johnsen SA, Monroe DG, Spelsberg TC, Westendorf JJ. Regulation of osteoblastic phenotype and gene expression by hop-derived phytoestrogens. J Steroid Biochem Mol Biol. 2005 ; 96 : 387-99. https://doi.org/10.1016/j.jsbmb.2005.04.038
  21. Humpel M, Isaksson P, Schaefer O, Kaufmanna U, Ciana P, Maggic A, Schleuning WD. Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with minimal trophic effects on the uterus. J Steroid Biochem Mol Biol. 2005 ; 97 : 299-305. https://doi.org/10.1016/j.jsbmb.2005.05.009
  22. Diel P, Thomae RB, Caldarelli A, Zierau O, Kolba S, Schmidt S, Schwab P, Metz P, Vollmer G. Regulation of gene expression by 8-prenylnaringenin in uterus and liver of Wistar rats. Planta Med. 2004 ; 70 : 39-44. https://doi.org/10.1055/s-2004-815453
  23. Pepper MS, Hazel SJ, Humpel M, Schleuning WD. 8-Prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol. 2004 ; 199 : 98-107. https://doi.org/10.1002/jcp.10460
  24. Zierau O, Morrissey C, Watson RWG, Schwab P, Kolba S, Metz P, Vollmer G. Antiandrogenic activity of the phytoestrogens naringenin, 6-(1,1-dimethylallyl) naringenin and 8-prenylnaringenin. Planta Med. 2003 ; 69 : 856-8 https://doi.org/10.1055/s-2003-43222
  25. Sathyamoorthy N, Wang TTY, Phang JM. Stimulation of pS2 expression by diet-derived compounds. Cancer Res. 1994 ; 54 : 957-61.
  26. Loven MA, Wood JR, Nardulli AM. Interaction of estrogen receptors α and β with estrogen response elements. Mol Cell Endocrinol. 2001 ; 181 : 151-63. https://doi.org/10.1016/S0303-7207(01)00491-9
  27. Lindsay R. The menopause and osteoporosis. Obstet Gynecol. 1996 ; 87 : 16S-9S. https://doi.org/10.1016/0029-7844(95)00430-0
  28. Oursler MJ. Direct and indirect effects of estrogen on osteoclasts. J Musculoskelet Neuronal Interact. 2003 ; 3 : 363-6.
  29. Nishikawa M, Akatsu T, Katayama Y, Yasutomo Y, Kado S, Kugal N, Yamamoto M, Nagata N. Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone. 1996 ; 18 : 9-14. https://doi.org/10.1016/8756-3282(95)00426-2
  30. Abrahamsen B. Bisphosphonate adverse effects, lessons from large databases. Curr Opin Rheumatol. 2010 ; 22(4) : 404-9. https://doi.org/10.1097/BOR.0b013e32833ad677
  31. Silverman SL, Lane NE. Glucocorticoid-induced osteoporosis. Curr Osteoporos Rep. 2009 ; 7(1) : 23-6. https://doi.org/10.1007/s11914-009-0005-4
  32. Cho SI. Effects of the Rehmanniae radix preparat on ovariectomized rats. Kor J Herbology. 2005 ; 20(4) : 61-7.
  33. Kim JH, Kim JY, Ann JY, Park HJ, Kim HJ, Kwak HB, Oh JM, Kim YK. Inhibitory effects of Achyranthis bidentatae radix on osteoclast differentiation and bone resorption. Kor J Herbology. 2010 ; 25(1) : 65-74.
  34. Hwang JS, Seo BI, Park JH, Roh SS, Kim MY, KimSM, Goo JS. Effect of Cervi cornu on treatment of osteoporosis in ovariectomized rats. Kor J Herbology. 2010 ; 25(2) : 1-10.
  35. Velarde MC. Pleiotropic actions of estrogen: a mitochondrial matter. Physiological Genomics. 2013 ; 45(3) : 106-9. https://doi.org/10.1152/physiolgenomics.00155.2012
  36. Hu P, Kinyamu HK, Wang L, Martin J, Archer TK, Teng C. Estrogen induces estrogen-related receptor alpha gene expression and chromatin structural changes in estrogen receptor (ER)-positive and ER-negative breast cancer cells. J Biol Chem. 2008 ; 283(11) : 6752-63. https://doi.org/10.1074/jbc.M705937200
  37. Lee E, Jang M, Lima TG, Kim T, Ha H, Lee JH, Hong HD, Cho CW. Selective activation of the estrogen receptor-β by the polysaccharide from Cynanchum wilfordii alleviates menopausal syndrome in ovariectomized mice. Int J Biol Macromol. 2020 ; 165(Pt A) : 1029-37. https://doi.org/10.1016/j.ijbiomac.2020.09.165
  38. Rasmussen TH, Nielsen, JB. Critical parameters in the MCF-7 cell proliferation bioassay (E-Screen). Biomarkers. 2002 ; 7(4) : 322-36. https://doi.org/10.1080/13547500210132907