Actaea racemosa

Cimicifuga racemosa

Ranunculaceae

Black cohosh, squawroot, black snakeroot, bug-bane, rattletop, richweed (2)

Rhizome and root (1)

Botany:

This herbaceous perennial grows to approximately 2.5m tall; has creamy white, tapering raceme spikes that are 30 to 60cm long, white stamens, tiny petals and sepals that fall away as the buds open from the base upwards (3). The leaves are green, serrated, compound and sharply toothed (4). Native to eastern North America and Canada, it prefers shady, moist woodlands and is collected in autumn (5). Rhizome is hard, knotty and externally brown, branching horizontal, 2 to 12cm in length, 1 to 2.5cm in thickness and slightly annulated. A few short roots can be white or brown inside and has thin bark. Microscopically the rhizome has a cortex consisting of collateral bundles of starch-bearing parenchymal cells separating the xylem, acute tracheids, numerous strongly lignified wood fibres and numerous pith cells (6).

History

Traditionally black cohosh was used by Indigenous North American tribes as a remedy for menstrual irregularities, childbirth, malaria, poor kidney function, sore throat and malaise. It is classified as a cool, dry herb with pungent, bitter and sweet qualities. It was valued in the treatment of constrictive respiratory conditions, various myalgia, anxiety, insomnia, nervous hyper-function and dysfunctional female reproductive organs. Large doses achieved diaphoretic activity, promoting detoxification in the case of snake and insect bites, as indicated by the common name black snakeroot (2, 7). Rheumatoid arthritis and tinnitus were others common ailments treated with this herb (2). Black cohosh has also been used in Korean folk medicine for pain and inflammation (7). In modern times, black cohosh has been used for the treatment of menopausal symptoms including 'climacteric symptoms (i.e. hot flashes and sweating), vulvovaginal atrophic symptoms (i.e. vaginal atrophy, vaginal dryness), impaired sexual function and possibly mood disorders' as well as for migraines (8).

Major Active Constituents

Actein, 27-deoxyactein, cimicifugoside M and cimicifugoside are the triterpene glycosides identified in black cohosh. Cimicifugoside M is the main chemical constituent distinguishing black cohosh (9, 10, 11). Aromatic acids, resin, caffeic and isoferulic acids, phytosterols, phenylpropanoid esters and cimiracemates are other common constituents (10).

Actions

Anti rheumatic, spasmolytic, oestrogen-modulating, uterine tonic (12);
Anti-inflammatory, antitussive, emmenagogue and sedative actions (13).

Pharmacology

Oestrogenic Activity
Black cohosh exerts a significant cytotxic effect on both oestrogen-sensitive and oestrogen-insensitive breast cancer cells. A reduction in cancerous cell growth was exhibited by synergism of black cohosh and Tamoxifen™ (anti-oestrogenic, selective oestrogen receptor modulator [SERM]) (14). Isopropyl extracts of black cohosh in concentrations of 2.5µg/ml and above also significantly inhibited proliferation of human mammary carcinoma cell line 435 as well as dose-dependant inhibition of the proliferation of mammary carcinoma cell line MCF-7 (15). The oestrogen- like effect of Black cohosh was thought to be due to an isoflavone, (formononectin) stimulating oestrogen receptors (8).

13 different Black cohosh rhizomes were collected from 13 different locations, extracted in 80% methanol, partially purified, and analysed using TLC and HPLC, photodiode array detector and mass spectrometer. Remifemin ™ and CimiPure ™ were also tested. There was no detected formononetin, or ononin (formononetin-7-glucoside) indicating that the oestrogen-like effects must be due to other active compounds (16). When an ethanolic Black cohosh extract (Ze 450) was trialled in a MCF-7 cell clone, ER-negative human breast cancer cell line T-47D was inhibited, representing the distinction between the growth inhibitory activity and anti-oestrogenic activity. Black cohosh inhibited transcription regulation of genes in cancerous cell lines 293T and T-47D and did not present progestin-like activity in the T-47D cell line (17). Oral Administration of Black cohosh did not promote oestrogen mammary gland tumours in vivo (10). Black cohosh had no effect on uterine weight, selectivity increased enzymatic activity at the oestrogen receptor and displayed luteinizing hormone (LH) suppression, possibly due to the triterpene glycosides acting upon the hypothalamus (1, 8, 15).

Anti-inflammatory Activity
Neutrophil elastase activity was inhibited in vitro by the compounds caffeic acid, fukinolic acid and cimicifugic acid isolated from a black cohosh rhizome. The reaction was dose dependant, and emphasized protective mechanisms for lung tissue against emphysematous changes (18). There has been some anti-inflammatory activity expressed in animal studies (19). Anti-allergic potential was expressed in vivo by significant inhibition of anti-IgE-induced passive cutaneous anaphylaxis (PCA) by a black cohosh extract. It also inhibited histamine release in rat peritoneal mast cells and inhibited cytokine gene expression IL-4, IL-5 and TNF-alpha mRNA in human leukemia mast cells (20).

Antioxidant Activity
The antioxidant capacity of 55 different herbs were assessed and compared against well known highly antioxidant herbs Silybum marianum (milk thistle) and Camellia sinensis (tea) leaf. The top 12 herbs, of which included black cohosh, were comparable to, or exceeded the antioxidant capacity of Silybum marianum and Camellia sinensis. This study was based on high scores of free radical scavenging activity (21).

Osteogenic Activity
In vitro, an ethanolic extract of black cohosh increased bone nodule formation in osteoblasts through gene enhancement of runx2 and osteocalcin at a dose of 500µg/mL. This action was oestrogen-receptor dependant and indicates the potential use of black cohosh in the prevention of osteoporosis in menopausal women (22). An isopropanolic extract of black cohosh standardized to 4500µg of triterpene glycosides was administered to ovariectized rat model of osteoporosis. There was a significant decrease in the urinary markers for bone loss and a reversal of bone loss beginning 2 weeks after the commencement of treatment and continued till week 7. These results highlight the appropriateness for long term clinical trials of black cohosh for the treatment of osteoporosis (23).

Dopaminergic
Black cohosh has demonstrated activity on dopaminergic-2 (D2) receptors, opposing prolactin and enhancing osteoblast activity therefore bettering libido and bone mineral density (8).

Serotonergic
The data from a study suggests that the mechanism by which a methanolic black cohosh preparation reduced hot flushes experienced by women, may not be due to oestrogenic properties, but may be mediated by strong binding capacity of black cohosh compounds with 5-HT (1A), 5-HT (1D) and 5-HT (7) serotonin receptor sites (24).

Prostatic Activity
Petasiphenone, a phenol isolated from black cohosh, inhibits the growth of the human prostate cancer cells LNCaP in vitro (25). Capacity for a black cohosh extract BNO 1055 to inhibit tumour proliferation induced by subcutaneous inoculation of LNCaP cells in immunodeficient mice proved successful. Tumour formation and size was significantly smaller than in the control group, indicating the possible application in the prevention and treatment of prostate cancer (26).

Clinical Outcome Studies

Menopausal symptoms (Climacteric complaints)
Menopause has been associated with an increased risk of osteoporosis, decreased view of one's own health (p=0.009) and notable decline in quality of life (8). The results are conflicting concerning the effectiveness of black cohosh for climacteric complaints. A 2006 randomized, double-blind, placebo-controlled trial, n=351, tested the efficacy of a black cohosh ethanol extract (160mg daily) for 1 year. Vasomotor symptoms, symptom intensity and Wiklund Vasomotor Symptom Subscale score did not differ for black cohosh compared to placebo p>0.05 (27). There was only limited superiority of black cohosh for climacteric complaints of moderate intensity compared to placebo in a recent multi-center, randomized placebo-controlled, double-blind parallel group study, n=122 over 12 weeks. The superiority was significant in the subgroup with a Kuppermen (menopause symptom) index > or =20 (p=<0.018) (28). When compared to a low-dose transdermal estradiol treatment in a RCT, n=64, the isopropanolic black cohosh preparation (40mg daily) was equivalent in decreasing hot flushes, vasomotor symptoms, anxiety and depression. Black cohosh raised HDL-cholesterol levels (p=<0.04) and lowered LDL-cholesterol levels (p=<0.003).

This study had provided the suggestion that black cohosh is a safe an effective alternative to low-dose transdermal estradiol therapy (29). A double-blind, multi-centre, RCT, measured the therapeutic effects of a black cohosh preparation (Klimadynon/Menofem 40mg), compared to a conjugated oestrogen (CO 0.6mg) and placebo (0.6mg) on 62 postmenopausal women. Black cohosh was equal to that of the conjugated oestrogen (CO) and superior to the placebo for menopausal rating and bone metabolism for both were improved. Black cohosh exerts beneficial effects on the brain, hypothalamus, bone and vagina. These results indicate that black cohosh may be an appropriate substitute for patients unable or unwilling to use conventional treatments (30).

Treatment of hot flushes and other symptoms in women with a history of breast cancer
There was no significant relief for breast cancer survivors from hot flushes and no change in follicle stimulating hormone (FSH) or luteinizing hormone (LH) among the black cohosh group in a RCT (n=85 where n=59 in Tamoxifen ™ group, n=42 in black cohosh group, and overall, 69 participants completed hot flush diaries) (31). In comparison a randomized study performed by the same author in 2003 using a combination therapy of a black cohosh preparation BNO 1055 (Menofem/Klimadynon ™, 20mg) and Tamoxifen ™ for 12 months resulted in almost 50% of participants becoming free of hot flushes (1). A 2008 review of hot flush studies conducted over the past two decades at the Mayo Clinic and the North Central Cancer Treatment Group revealed that black cohosh did not substantially decrease hot flushes. The investigators reviewed 10 randomized, controlled, (eight placebo-controlled) double-blind trials involving a total of 1,581 women and 3 placebo-controlled, double-blind clinical trials involving 329 men, 14 pilot trials with 329 participants and concluded that therapy results did not seem to differ for women regardless of breast cancer history or Tamoxifen ™ use (32). Commercially available black cohosh with a maximum triterpene content of 2.5% had no effect on oestrogenic markers in serum, pS2 or systemic oestrogen but menopausal symptoms were relieved during the 12 week trial. Increased confidence in the safety and efficacy is represented by these results(33), whilst the systemic oestrogen-like effects could not be denied by Borrelli and Ernst in a systematic review in 2002 (34).

A 2008 review of black cohosh in the treatment of vasomotor symptoms has shown that black cohosh significantly reduces the severity or frequency of hot flushes (35) and menopausal depression and anxiety (36). Contradictory results are apparent regarding randomized, placebo-controlled, double-blind clinical trials (35). Despite the conflicting reviews, black cohosh has been approved by the Jefferson College of Pharmacy and The North American Menopause Society for the treatment of mild vasomotor symptoms in women not involved in other therapies and not for more than 6 months (37, 1).

Premenstrual Syndrome
Black cohosh has been found to be effective in reducing emotional symptoms of premenstrual syndrome such as anxiety, depression and irritability (38). Commission E has approved black cohosh for the treatment of premenstrual syndrome and dysmenorrhoea (39).

Other uses
A standardized 50mg black cohosh herbal combination RCT trial decreased the average frequency of menstrual induced migraine in the active group (1).

Indications

• Menopausal symptoms (10)
• Menstruation disorders (spasmodic dysmenorrhoea, premenstrual syndrome, (10, 40, 12, 41) amenorrhoea, menorrhagia, ovarian pain) (40, 12, 41)
• Ovarian dysfunctional and insufficiency (1)
• Osteoarthritis (especially small joint) (10)
• Rheumatism, arthritis (10, 3, 40, 12)
• Late pregnancy labour preparation (10, 12)
• Myalgia (10, 12)
• Tinnitus (10, 3, 40, 12, 41)
• Neuralgia (40, 12, 41)
• Sciatica (40, 12, 41)
• Respiratory tract disorders (whooping cough, asthma) (40, 12)
• Chorea (12)
• Female infertility, leukorrhea (12)
• Hormonal migraine (41)
• Scarlett fever, fatty heart (41)

Contra-indications and cautions

• Caution in people with oestrogen-dependant tumours, use under professional supervision (13)
• Do not use in pregnancy and lactation (except in the last few weeks to assist with birth) (42, 10)
• Not for children under 12 years (15)
• Do not use for more than 6 months (43)

Adverse effects
Large doses may cause dizziness, headache, tremors or giddiness. GIT disturbance and rashes are the most common (13, 43). Adverse effects tend to be mild, rare and reversible (1). Black cohosh may have had a role in the myopathy observed in a patient presenting severe asthenia and very high muscle enzyme serum levels (44). Reported Hepatic Reactions
42 cases of suspected hepatotoxic reactions have been noted by The European Medicine Agency and the Committee on Herbal Medicine Products. All cases were poorly reported, two were possible and two probable. Many of the reports are confounded by the use of other medication (45). The Adverse Drug Reactions Advisory Committee (ADRAC) received 16 reports of suspected hepatotoxicity with black cohosh, eleven considered causally related and 1 considered certainly related. An Expert Advisory Group convened by the Therapeutic Goods Administration (TGA) critically reviewed the safety and efficacy of black cohosh and concluded that 'there appears to be a very rare association between consumption of black cohosh and liver toxicity' (46). Black cohosh is still considered suitable for use in complementary medicines but new cautionary labelling is advised by the Dietary Supplement Information Expert Committee (46, 47). Significant Interactions
Black cohosh did affect, but not significantly, CYP2d6 in vivo, indicating it has a potential to interact with drugs that also act on this cytochrome (48), however no adverse interactions have been reported between black cohosh and prescription medicines (49). Toxicity
Nausea, vomiting, vertigo and visual disturbances have been associated with overdose (1).

Posology

• 0.3-2g three times daily (Decoction or powdered root) (1)
• 10 to 20 mL/week (1:2 liquid) (10)
• 300 to 400 mg/day (tablet) (10)

References

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8. Leach JM, Moore V. Black cohosh (Cimcifuga spp.) for menopausal symptoms. (Protocol). Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD007244. DOI: 10.1002/14651858.CD007244. Accessed 12 September 2008.

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20. Kim CD et al. Inhibition of mast cell-dependant allergy reaction by extract of Black cohosh (Cimicifuga racemosa). Immunopharmacology And Immunotoxixology 2004;26(2):299-308. [Abstract online]. Available: Ebsco/Medline. [9 September 2008]

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23. Nisslein T, Freudenstein J. Effects of an isopropanolic extract on urinary crosslinks and other parameters of bone quality in an overiectomized rat model of osteoporosis. Journal of Bone and Mineral Metabolism 2003;21:360-6. [Abstract online]. Available: EBSCO/Medline. [9 September 2008]

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This monograph was authored in 2008 by Crystal Whitney, a student in Southern Cross University's Bachelor of Naturopathy programme, and edited by Nena Aleschewski BNat. While the author and editor have strived to cite published information accurately, Southern Cross University will not be responsible for any inaccuracies that may have occurred.

This information is provided for educational purposes only and does not constitute medical advice. If you wish to use herbal medicine as part of your health care, seek the advice of an appropriately qualified practitioner.