Effects of Aqueous Extracts of Cynanchum wilfordii in Rat Models for Postmenopausal Hot Flush

  • Lee, Gyuok (Division of Food and Nutrition, Chonnam National University) ;
  • Choi, Chul-yung (Jeollanamdo Institute of Natural Resources Research) ;
  • Jun, Woojin (Division of Food and Nutrition, Chonnam National University)
  • Received : 2016.07.07
  • Accepted : 2016.09.01
  • Published : 2016.12.31


Menopausal hot flushes (HFs), which manifest as a transient increase in skin temperature, occur most frequently in postmenopausal women, and sometimes negatively influence daily life. We investigated the effect of an aqueous extract of Cynanchum wilfordii (CWW) in a rat model of menopausal HFs, where tail skin temperature (TST) is increased after the rapid estrogen decline induced by ovariectomy. Ten-week-old female rats were ovariectomized and treated with CWW for 1 week. We measured TST and rectal temperatures (RT) and investigated serum estradiol. The TST in ovariectomized (OVX) rats was significantly elevated after ovariectomy compared with control rats, whereas the RT in OVX rats was not elevated. Administration of CWW (200 mg/kg/d for 7 days, p.o.) significantly improved the skin temperature increase in OVX rats. The lower level of serum estradiol in OVX rats was significantly increased by supplying E2, but it was not affected by CWW. The present study indicates a need for future research involving treatment with high concentrations of C. wilfordii and measurement over 24 h.


  1. Kronenberg F. 1990. Hot flashes: epidemiology and physiology. Ann NY Acad Sci 592: 52-86.
  2. Shen W, Stearns V. 2009. Treatment strategies for hot flushes. Expert Opin Pharmacother 10: 1133-1144.
  3. Freedman RR. 2001. Physiology of hot flashes. Am J Hum Biol 13: 453-464.
  4. Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. 2002. Pathophysiology and treatment of hot flashes. Mayo Clin Proc 77: 1207-1218.
  5. Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes DF. 2002. Hot flushes. Lancet 360: 1851-1861.
  6. Chambliss KL, Shaul PW. 2002. Estrogen modulation of endothelial nitric oxide synthase. Endocr Rev 23: 665-686.
  7. Florian M, Lu Y, Angle M, Magder S. 2004. Estrogen induced changes in Akt-dependent activation of endothelial nitric oxide synthase and vasodilation. Steroids 69: 637-645.
  8. Orshal J, Khalil R. 2004. Gender, sex hormones, and vascular tone. Am J Physiol Regul Integr Comp Physiol 286: R233-R249.
  9. Guo X, Razandi M, Pedram A, Kassab G, Levin ER. 2005. Estrogen induces vascular wall dilation: mediation through kinase signaling to nitric oxide and estrogen receptors $\alpha$ and $\beta$. J Biol Chem 280: 19704-19710.
  10. Guo X, Lu X, Ren H, Levin ER, Kassab GS. 2006. Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide. Am J Physiol Heart Circ Physiol 290: H1788-H1797.
  11. Xing D, Nozell S, Chen YF, Hage F, Oparil S. 2009. Estrogen and mechanisms of vascular protection. Arterioscler Thromb Vasc Biol 29: 289-295.
  12. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. 2002. Risks and benefits of estrogen plus progestin in healthy post-menopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288: 321-333.
  13. Carroll DG, Kelley KW. 2009. Use of antidepressants for management of hot flashes. Pharmacotherapy 11: 1357-1374.
  14. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. 2003. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95: 1758-1764.
  15. Chang A, Kwak BY, Yi K, Kim JS. 2012. The effect of herbal extract (EstroG-100) on pre-, peri- and post-menopausal women: a randomized double-blind, placebo-controlled study. Phytother Res 26: 510-516.
  16. Lee KH, Lee DJ, Kim SM, Je SH, Kim EK, Han HS, Han IK. 2005. Evaluation of effectiveness and safety of natural plants extract ($Estromon^{(R)}$) on perimenopausal women for 1 year. J Korean Soc Menopause 11: 16-26.
  17. Freedman RR, Krell W. 1999. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol 181: 66-70.
  18. Kronenberg F, Mallory B, Downey JA. 1993. Women's health: new frontiers in rehabilitation medicine. Arch Phys Med Rehabil 74: 1377-1378.
  19. Kobayashi T, Ushijima O, Chen JT, Shiraki M, Ohta T, Kiyoki M. 1995. Basal tail skin temperature elevation and augmented response to calcitonin gene-related peptide in ovariectomized rats. J Endocrinol 146: 431-437.
  20. Berendsen HH, Weekers AH, Kloosterboer HJ. 2001. Effect of tibolone and raloxifene on the tail temperature of oestrogen-deficient rats. Eur J Pharmacol 419: 47-54.
  21. Opas EE, Rutledge SJ, Vogel RL, Rodan GA, Schmidt A. 2004. Rat tail skin temperature regulation by estrogen, phytoestrogens and tamoxifen. Maturitas 48: 463-471.
  22. Sipe K, Leventhal L, Burroughs K, Cosmi S, Johnston GH, Deecher DC. 2004. Serotonin 2A receptors modulate tailskin temperature in two rodent models of estrogen deficiency-related thermoregulatory dysfunction. Brain Res 1028: 191-202.
  23. Bowe J, Li XF, Kinsey-Jones J, Heyerick A, Brain S, Milligan S, O'Byrne K. 2006. The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. J Endocrinol 191: 399-405.
  24. Wright BE, Katovich MJ. 1996. Effect of restraint on druginduced changes in skin and core temperature in biotelemetered rats. Pharmacol Biochem Behav 55: 219-225.
  25. Freedman RR, Norton D, Woodward S, Cornelissen G. 1995. Core body temperature and circadian rhythm of hot flashes in menopausal. J Clin Endocrinol Metab 80: 2354-2358.
  26. Kobayashi T, Tamura M, Hayashi M, Katsuura Y, Tanabe H, Ohta T, Komoriya K. 2000. Elevation of tail skin temperature in ovariectomized rats in relation to menopausal hot flushes. Am J Physiol Regul Integr Comp Physiol 278: R863-R869.
  27. Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, Ogawa S, Inoue S, Muramatsu M, Masamune Y. 2001. Interaction of Phytoestrogens with Estrogen Receptors $\alpha$ and $\beta$. Biol Pharm Bull 24: 351-356.
  28. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor $\beta$. Endocrinology 139: 4252-4263.
  29. Diel P, Olff S, Schmidt S, Michna H. 2001. Molecular identification of potential selective estrogen receptor modulator (SERM) like properties of phytoestrogens in the human breast cancer cell line MCF-7. Planta Med 67: 510-514.
  30. Jisa E, Dornstauder E, Ogawa S, Inoue S, Muramatsu M, Jungbauer A. 2001. Transcriptional activities of estrogen receptor alpha and beta in yeast properties of raloxifene. Biochem Pharmacol 62: 953-961.

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