Black Cohosh (Cimicifuga racemose)

Cimicifuga racemose, also known as Black cohosh, is a member of the buttercup family and grows in North America.

Black Cohosh (Cimicifuga racemose)

Uses

Native Americans traditionally used black cohosh for a variety of ailments and introduced it to European colonists. Currently, black cohosh is used as a dietary supplement for hot flashes and other menopausal symptoms. It has also been promoted for other conditions, including menstrual cramps and premenstrual syndrome, and to induce labor. The part of the black cohosh plant used in herbal preparations is the root or rhizome (underground stem).

German Commission E approved the use of black cohosh root for premenstrual discomfort and dysmenorrhea or climacteric (menopausal) neurovegetative ailments. Acteina, a constituent in black cohosh, has been studied for use in treating peripheral arterial disease.

Chemistry/Pharmacology

Constituents include oleic, palmitic, and salicylic acids; cimigonite; tannin; and volatile oil.

Clinical Studies

Modern clinical studies have investigated the therapeutic efficacy and safety of black cohosh extracts for indications of the neurovegetative symptoms caused by menopause. These studies used several internationally recognized and validated scales as controls, including Kupperman's Menopause Index for the quantitative determination of menopausal symptoms, the Self-evaluation Depression Scale, the Profile of Mood States, the Hamilton Anxiety Scale, and the Clinical Global Impression scale (CGI), for evaluating the success and the risk-to-benefit assessment of the treatment. Somatic symptoms were determined using vaginal-cytological controls, such as vaginal smears, and measures of gonadotropin secretion.

Clinical studies using hormone replacement therapy (HRT) and black cohosh have been published based on a particular product called Remifemin®, standardized based on triterpene glycosides; each tablet contains 1 mg of triterpenes, calculated as 27-deoxyacteine and totaling 40 mg of black cohosh extract. In 1996, nearly ten million monthly units of Remifemin were sold in Germany, Australia, and the United States. At least eight clinical studies have been published on the therapeutic effects of Remifemin in treating menopausal symptoms although the total in the literature, according to the Napralert database, is 19.

Two studies examined the efficacy of Remifemin in 86 women with climacteric complaints who were at risk with HRT, or who wanted a natural alternative. One open study treated 36 women who either showed contraindications to HRT or wished to be treated with a hormone-free preparation. They were given liquid Remifemin (40 drops twice daily) for 12 weeks. The decrease in values of the Kupperman index was highly significant in the treatment group, as was the improvement in the most frequent climacteric symptoms. Also highly significant was the positive change in the Clinical Global Impression scale. No side effects or incompatibility reactions were observed during the three-month trial. In the other open study, 50 women with menopausal complaints were also treated with 40 drops twice daily of liquid Remifemin for 12 weeks. Thirty-nine patients had shown contraindications to HRT, and 11 had refused hormone treatment. Improvements in the somatic findings, neurovegetative and psychic symptoms and signs, and the Profile of Mood State and Clinical Global Impression scales were all rated significant to highly significant in the treatment group. No serious side effects were observed, with only mild gastrointestinal disturbances in four patients, and in no case did the treatment need to be discontinued.

It has also been shown to exhibit anti-osteoporotic effects and thus enhances bone formation. Clinical studies indicate that black cohosh by itself, or in combination with other herbs, is effective in the treatment of menopausal symptoms.

Investigations of black cohosh found it effective in treating menopausal syndrome induced by luteinizing hormone-releasing hormone analogue (LHRH-a). It has also been reported to improve sleep.

Preclinical findings indicate that black cohosh decreased the proliferation of prostate cancer cells and induced an apoptotic response in liver cells.

Black cohosh should not be confused with blue cohosh, which has a different medicinal profile. It is also not clear whether black cohosh acts as a phytoestrogen. Patients with breast cancer or at risk of breast cancer should consult with their physicians before taking it.

Biomechanical Mechanism

Black cohosh relieves menopausal symptoms likely by mimicking neurotransmitters: dopaminergic, noradrenergic, serotoninergic, and GABAergic effects have been demonstrated. It was believed to have estrogenic effects due to its ability to relieve menopausal symptoms in women. However, studies show that it does not affect the levels of LH, FSH, prolactin, or estradiol. A black cohosh extract was shown to have antiproliferative and antiestrogenic effects in ER-negative cells, which suggests that such effects are mediated via an estrogen-independent pathway, possibly through HER-2 signaling.

In other studies, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited proliferation of HepG2, p53 positive, liver cells. In prostate cancer cells, it demonstrated antiproliferative effects, via impaired equilibrated nucleoside transporter (ENT) activity, resulting in hindered nucleoside uptake. Black cohosh was also reported to induce apoptosis and suppress estradiol-induced cell proliferation in human endometrial adenocarcinoma cells.

Sources/Articles

Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: a randomized, double blind, parallel-controlled study versus tibolone. Maturitas. Sep 20 2007;58(1):31-41.

Bebenek M, Kemmler W, von Stengel S, Engelke K, Kalender WA. Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone mineral density, 10-year coronary heart disease risk, and menopausal complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen (TRACE) study. Menopause. 2010 Jul;17(4):791-800.

Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John’s wort for symptom-specific climacteric treatment—results of a large-scale, controlled, observational study. Maturitas. Aug 20 2007;57(4):405-414.

Chan BY, Lau KS, Jiang B, Kennelly EJ, Kronenberg F, Kung AW. Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells. Bone. 2008 Sep;43(3):567-73.

Dai X, Liu J, Nian Y, Qiu MH, Luo Y, Zhang J. A novel cycloartane triterpenoid from Cimicifuga induces apoptotic and autophagic cell death in human colon cancer HT-29 cells. Oncol Rep. 2017 Apr;37(4):2079-2086.

Dueregger A, Guggenberger F, Barthelmes J, et al. Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055. Phytomedicine. 2013 Nov 15;20(14):1306-14.

Duker EM, Kopanski L, Jarry H, Wuttke W. Effects of extracts of Cimicifuga racemosa (Remifemin) on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420.

Einbond LS, Wen-Cai Y, He K, et al. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. Jun 2008;15(6-7):504-511.

Foster, Steven. "Black Cohosh." In Tyler's Honest Herbal, pp. 81-84. Routledge, 1999. https://www.taylorfrancis.com/chapters/edit/10.4324/9780203819692-10/black-cohosh

Garita-Hernandez M, Calzado MA, Caballero FJ, et al. The growth inhibitory activity of the Cimicifuga racemosa extract Ze450 is mediated through estrogen and progesterone receptors-independent pathways. Planta Med 2006:72(4):317-23.

Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas. 2003 Mar 14;44 Suppl 1:S59-65.

Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739-45.

Jarry H, Stromeier S, Wuttke W, Nahrstedt A. Petasiphenone, a phenol isolated from Cimicifuga racemosa, in vitro inhibits proliferation of the human prostate cancer cell line LNCaP. Planta Med. Feb 2007;73(2):184-187.

Jiang K, Jin Y, Huang L, et al. Black cohosh improves objective sleep in postmenopausal women with sleep disturbance. Climacteric. 2015;18(4):559-67.

Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012 Sep 12;9:CD007244.

Liske E, et al. Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Women Health Gend Based Med 2002;11:163-74.

Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Ther. Jan-Feb 1998;15(1):45-53.

Low Dog T, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. Jul-Aug 2003;10(4):299-313.

Moser C, Vickers SP, Brammer R, Cheetham SC, Drewe J. Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice.Phytomedicine. 2014 Sep 25;21(11):1382-9.

Philp, Hazel A. "Hot flashes-a review of the literature on alternative and complementary treatment approaches." Alternative Medicine Review 8, no. 3 (2003): 284-302.
http://www.anaturalhealingcenter.com/documents/Thorne/articles/hot_flashes.pdf

Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer. Apr 1 2007;120(7):1523-1528.

Reed SD, Newton KM, LaCroix AZ, et al. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause. 2008 Jan-Feb;15(1):51-8.

Shams T, Setia MS, Hemmings R, et al. Efficacy of black cohosh-containing preparations on menopausal symptoms: a meta-analysis. Altern Ther Health Med. 2010 Jan-Feb;16(1):36-44.

Sen A.Orobuccolingual dyskinesia after long-term use of black cohosh and ginseng. J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):E50.

Wang C, Huang Q, Liang CL, et al. Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer. J Ethnopharmacol. 2019 Jun 28;238:111840.

Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D.The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa). J Steroid Biochem Mol Biol. 2014 Jan;139:302-10.

Zepelin HH, Meden H, Kostev K, et al. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther. Mar 2007;45(3):143-154.

Zierau O, Bodinet C, Kolba S, et al. Antiestrogenic activities of Cimicifuga racemosa extracts. J Steroid Biochem Mol Biol 2002;80:125-30.