Black Cohosh (Actaea racemosa L.) Improves Serum Lipid Profiles and Vasomotor Responses in Ovariectomized Rats

Eun-Young Kim¹, Ah-Young Song¹, Yiseul Kim¹, Byung-Koo Yoon², YoungJoo Lee³ and Mee-Ra Rhyu^1,

¹Division of Functional Food Research, Korea Food Research Institute, Gyeonggi-do, Republic of Korea

²Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

³Department of Bioscience and Biotechnology, College of Life Science, Sejong University, Seoul, Republic of Korea

Cite this paper:
Eun-Young Kim, Ah-Young Song, Yiseul Kim, Byung-Koo Yoon, YoungJoo Lee and Mee-Ra Rhyu. Black Cohosh (Actaea racemosa L.) Improves Serum Lipid Profiles and Vasomotor Responses in Ovariectomized Rats. Journal of Food and Nutrition Research. 2017; 5(8):539-544. doi: 10.12691/jfnr-5-8-2

Abstract

We investigated the effects of long-term administration of black cohosh extract (BcEx) on serum lipid profiles and vasomotor responses in ovariectomized (OVX) rats and compared them with those of rats administered 17¦Â-estradiol (E2) or raloxifene, a selective estrogen receptor modulator. Vehicle (OVX- or sham-control), BcEx (0.5 or 3.0 mg/kg/day), E2 (0.5 mg/kg/day), or raloxifene (2.5 mg/kg/day) were injected subcutaneously for 5 weeks, and serum lipid profiles and vasomotor responses were measured at the end of the treatment. BcEx lowered total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, but did not affect high-density lipoprotein cholesterol or triglyceride (TG) levels. Raloxifene showed a similar effect to that of BcEx, while E2 attenuated the increase in TC and LDL-C levels and significantly increased TG levels. The vascular relaxation induced by carbachol increased significantly in norepinephrine-precontracted aortic rings isolated from BcEx-, E2-, or raloxifene-treated rats. No change in uterine weight was observed in the BcEx-treated group. The raloxifene-treated group showed a similar trend as that of the BcEx-treated group, but E2 significantly increased uterine weight. These results suggest that long-term administration of BcEx behaves similar to the selective estrogen receptor modulator raloxifene.

Keywords:
black cohosh ovariectomy lipid profiles vasomotor responses selective estrogen receptor modulators

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References:

[1]	Palacios, S, "Current perspectives on the benefits of HRT in menopausal woman," Maturitas, 33 (Suppl 1). S1-S13. Nov 1999.
[2]	Stampfer, M.J., Colditz, G.A., Willett, W.C., Manson, J.E., Rosner, B. and Speizer, F.E, "Postmenopausal estrogen therapy and cardiovascular disease: Ten-year follow-up from the nurses' health study", New England Journal of Medicine, 325 (11). 756-762. Sep 1991.
[3]	Wuttke, W., Jarry, H., Becker, T., Schultens, A., Christoffel, V., Gorkow, C. and Seidlova-Wuttke, D, "Phytoestrogens: endocrine disrupters or replacement of hormone replacement therapy?", Maturitas, 44 (Suppl 1). S9-S20. Mar 2003.
[4]	Seidlova-Wuttke, D., Jarry, H. and Wuttke, W, "Effects of estradiol benzoate, raloxifene and an ethanolic extract of Cimicifuga racemosa in nonclassical estrogen regulated organs of ovariectomized rats", Planta Medica, 75 (12). 1279-1285. Oct 2009.
[5]	Anthony, M., Williams, J.K. and Dunn, B.K, "What would be the properties of an ideal SERM?", Annals New York Academy of Sciences, 949. 261-278. Dec 2001.
[6]	Bracamonte, M.P., Rud, K.S. and Miller, V.M, "Mechanism of raloxifene-induced relaxation in femoral veins depends on ovarian hormonal status", Journal of Cardiovascular Pharmacology, 39 (5). 704-713. May 2002.
[7]	Sutherland, M.K., Brady, H., Gayo-Fung, L.M., Leisten, J., Lipps, S.G., McKie, J.A., O'Leary, E., Patnaik, N., Anderson, D.W., Bhagwat, S.S. and Stein, B, "Effects of SP500263, a novel selective estrogen receptor modulator, on bone, uterus, and serum cholesterol in the ovariectomized rat", Calcified Tissue International, 72 (6). 710-716. Jun 2003.
[8]	Borrelli, F. and Ernst, E, "Cimicifuga racemosa: a systematic review of its clinical efficacy", European Journal of Clinical Pharmacology, 58 (4). 235-241. Jul 2002.
[9]	Osmers, R., Friede, M., Liske, E., Schnitker, J., Freudenstein, J. and Henneicke-von Zepelin, H.H, "Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms", Obstetrics and Gynecology, 105 (5 Pt 1). 1074-1083. May 2005.
[10]	Geller, S.E., Shulman, L.P., Breemen, R.B., Banuvar, S., Zhou, Y., Epstein, G., Hedayat, S., Nikolic, D., Krause, E.C., Piersen, C.E., Bolton, J.L., Pauli, G.J. and Farnsworth, N.R, "Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial", Menopause, 16 (6). 1156-1166. Nov-Dec 2009.
[11]	Seidlova-Wuttke, D., Jarry, H., Becker, T., Christoffel, V. and Wuttke, W, "Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus", Maturitas, 44 (Suppl 1). S39-S50. Mar 2003.
[12]	Rachon, D., Rortherms, T., Seidlova-Wuttke, D. and Wuttke, W, "Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprageu-Dawley rat", Maturitas, 60 (3-4). 209-215. Jul-Aug 2008.
[13]	Kim, E.Y., Lee, Y.J. and Rhyu, M.R, "Black cohosh (Cimicifuga ragemosa) relaxes the isolated rat thoracic aorta through endothelium-dependent and -independent mechanisms", Journal of Ethnopharmacology, 138 (2). 537¨C542. Nov 2011.
[14]	Wong, C.M., Yao, X., Au, C.L., Tsang, S.Y., Fung, K.P., Laher, I., Vanhoutte, P.M. and Huang, Y, "Raloxifene prevents endothelial dysfunction in aging ovariectomized female rats", Vascular Pharmacology, 44 (5). 290-298. Mar 2006.
[15]	Simoncini, T., Genazzani, A.R. and Liao, J.K, "Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene", Circulation, 105 (11). 1368-1373. Mar 2002.
[16]	Rhyu, M.R., Lu, J., Webster, D.E., Fabricant, D.S., Farnsworth, N.R. and Wang, Z.J, "Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human ¦Ì opiate receptor", Journal of Agricultural and Food Chemistry, 54 (26). 9852-9857. Dec 2006.
[17]	Burdette, J.E., Liu, J., Chen, S.N., Fabricant, D.S., Piersen, C.E., Barker, E.L., Pezzuto, J.M., Mesecar, A., Breemen, R.B., Farnsworth, N.R. and Bolton, J.L, "Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor", Journal of Agricultural and Food Chemistry, 51 (19). 5661-5670. Sep 2003.
[18]	Xu, H., Fabricant, D.S., Piersen, C.E., Bolton, J.L., Mezzute, J.M., Fong, H., Totura, S., Farnsworth, N.R. and Constantinou, A.I, "A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health", Phytomedicine, 9 (8). 757-762. Dec 2002.
[19]	Friedwald, W., Levy, R. and Fredrickson, D, "Estimation of the concentration of low density lipoprotein in plasma without use of preparative ultracentrifuge", Clinical Chemistry, 18 (6). 499-502. Jun 1972.
[20]	Frolik, C.A., Bryant, H.U., Black, E.C., Magee, D.E. and Chandrasekhar, S, "Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate", Bone, 18 (6). 621-627. Jun 1996.
[21]	White, C.R., Shelton, J., Chen, S.J., Darley-Usmar, V., Allen, L., Nabors, C., Sanders, P.W., Chen, F. and Oparil, S, "Estrogen restores endothelial cell function in an experimental model of vascular injury", Circulation, 96 (5). 1624-1630. Sep 1997.
[22]	Delmas, P.D., Bjarnason, N.H., Mitlak, B.H., Ravoux, A.C., Shah, A.S., Huster, W.J., Draper, M. and Christiansen, C, "Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women", New England Journal of Medicine, 337 (23). 1641-1647. Dec 1997.
[23]	Hammond, C.B, "Women's concerns with hormone replacement therapy: Compliance issues", Fertility and Sterility, 62 (6 Suppl 2). 157S-160S. Dec 1994.
[24]	Ateba. S.B., Njamen, D., Medjakovic, S., Hobiger, S., Mbanya, J.C., Jungbauer, A. and Krenn, L, "Eriosema laurentii De Wild (leguminosae) methanol extract has estrogenic properties and prevents menopausal symptoms in ovariectomized Wistar rats", Journal of Ethnopharmacology, 150 (1). 298-307. Oct 2013.
[25]	Christodoulakos, G.E., Lambrinoudaki, I.V. and Botsis, D.C, "The cardiovascular effects of selective estrogen receptor modulators", Annals New York Academy of Science, 1092. 374-384. Dec 2006.
[26]	Walsh, B.W., Kuller, L.H., Wild, R.A., Paul, S., Farmer, M., Lawrence, J.B., Shah, A.S. and Anderson, P.W, "Effects of raloxifenen on serum lipids and coagulation factors in healthy postmenopausal women" JAMA, 279 (18). 1445-1451. May 1998.
[27]	Arenas, L.A., Armstrong, S.J., Xu, Y. and Davidge, S.T, "Chronic tumor necrosis is factor-alpha inhibition enhances NO modulation of vascular function in estrogen-deficient rats", Hypertension, 46 (1). 76-81. Jul 2005.
[28]	Figtree, G.A., Lu, Y., Webb, C.M. and Collins, P, "Raloxifene acutely relaxes rabbit coronary arteries in vitro by an estrogen receptor-dependent and nitric oxide-dependent mechanism" Circulation, 100 (10). 1095-1101. Sep 1999.
[29]	Paredes-Carbajal, M.C., Juarez-Oropeza, M.A., Ortiz-Mendoza, C.M. and Mascher, D, "Effects of acute and chronic estrogenic treatment on vasomotor responses of aortic rings from ovariectomized rats", Life Sciences, 57 (5). 473-486. Jun 1995.
[30]	Lamas, A.Z., Caliman, I.F., Dalpiaz, P.L.M., Ferreira de Melo, Jr. A., Abreu, G.R., Lemos, E.M., Gouvea, S.A. and Bissoli, N.S, "Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats", Life Sciences, 124 (1). 101-109. Mar 2015.