Actaea racemosa
Actaea racemosa 002.JPG
Inflorescence

Apparently Secure (NatureServe)
Scientific classification edit
Kingdom: Plantae
Clade: Tracheophytes
Clade: Angiosperms
Clade: Eudicots
Order: Ranunculales
Family: Ranunculaceae
Genus: Actaea
Species:
A. racemosa
Binomial name
Actaea racemosa
Synonyms[1]
Synonymy
  • Cimicifuga repens (L) Nutt
  • Cimicifuga americana Muhl
  • Actaea gyrostachya Wender
  • Actaea monogyna Walter
  • Actaea orthostachya Wender
  • Botrophis actaeoides Raf ex Fisch & CA Mey
  • Botrophis pumila Raf
  • Botrophis serpentaria Raf

Actaea racemosa, the black cohosh, black bugbane, black snakeroot, or fairy candle (syn. Cimicifuga racemosa), is a species of flowering plant of the family Ranunculaceae. It is native to eastern North America from the extreme south of Ontario to central Georgia, and west to Missouri and Arkansas. It grows in a variety of woodland habitats, and is often found in small woodland openings. The roots and rhizomes were used in traditional medicine by Native Americans. Its extracts are manufactured as herbal medicines or dietary supplements. Thereof, most of the dietary supplements containing black cohosh are not well-studied or recommended for safe and effective use in treating menopause symptoms or any disease.[2] In contrast, some herbal medicinal products containing black cohosh (cimicifuga racemosa) extract hold a marketing authorization in several states of the European Union are well-studied and recommended for safe and effective use for the relief of menopausal symptoms (i.e. in the years around menopause) such as hot flushes and profuse sweating attacks.[3] Such differentiation between the product types seems to be important.[4][5][6]

Taxonomy

The plant species has a history of taxonomic uncertainty dating back to Carl Linnaeus, who—on the basis of morphological characteristics of the inflorescence and seeds—had placed the species into the genus Actaea. This designation was later revised by Thomas Nuttall reclassifying the species to the genus Cimicifuga. Nuttall's classification was based solely on the dry follicles produced by black cohosh, which are typical of species in Cimicifuga.[7] However, recent data from morphological and gene phylogeny analyses demonstrate that black cohosh is more closely related to species of the genus Actaea than to other Cimicifuga species. This has prompted the revision to Actaea racemosa as originally proposed by Linnaeus.[7] Blue cohosh (Caulophyllum thalictroides), despite its similar common name belongs to another family, the Berberidaceae, is not closely related to black cohosh, and may be unsafe if used together.[8]

Description

Black cohosh is a smooth (glabrous) herbaceous perennial plant that produces large, compound leaves from an underground rhizome, reaching a height of 25–60 cm (9.8–23.6 in).[9][10] The basal leaves are up to 1 m (3 ft 3 in) long and broad, forming repeated sets of three leaflets (tripinnately compound) having a coarsely toothed (serrated) margin.

The flowers are produced in late spring and early summer on a tall stem, 75–250 cm (30–98 in) tall, forming racemes up to 50 cm (20 in) long. The flowers have no petals or sepals, and consist of tight clusters of 55–110 white, 5–10 mm (0.20–0.39 in) long stamens surrounding a white stigma. The flowers have a distinctly sweet, fetid smell that attracts flies, gnats, and beetles.[9]

The fruit is a dry follicle 5–10 mm (0.20–0.39 in) long, with one carpel, containing several seeds.[7]

Cultivation

A. racemosa grows in dependably moist, fairly heavy soil. It bears tall tapering racemes of white midsummer flowers on wiry black-purple stems, whose mildly unpleasant, medicinal smell at close range gives it the common name "Bugbane". The drying seed heads stay handsome in the garden for many weeks. Its deeply cut leaves, burgundy colored in the variety "atropurpurea", add interest to gardens, wherever summer heat and drought do not make it die back, which make it a popular garden perennial. It has gained the Royal Horticultural Society's Award of Garden Merit.[11]

Use as medicine

Historical use

Native Americans used black cohosh to treat gynecological and other disorders.[2][10][12] Following the arrival of European settlers in the U.S. who continued the use of black cohosh, the plant appeared in the U.S. Pharmacopoeia under the name "black snakeroot".[2] In the 19th century, the root was used to treat snakebite, inflamed lungs, and pain from childbirth.[13]

Current use

Nowadays, extracts from the underground parts of the plant —the rhizome (Cimicifugae racemosae rhizoma) and the root (Cimicifugae racemosae radix)— are used medicinally. The rhizomes and roots contain various saponins (triterpene saponins/triterpene glycosides such as actein) as well as cimifugic acids and other phenol carboxylic acids.[3][14] The active substance comprises the total extract.[3]

In most European countries, China, Malaysia, Thailand, Argentina and some other countries, black cohosh products are available as herbal medicinal products which have been approved by regulatory authorities ensuring reliable pharmaceutical quality, safety and efficacy for the relief of menopausal complaints such as hot flushes and profuse sweating.[3] In the U.S., India, and some other countries, Black cohosh is used as a dietary supplement marketed mainly to women for treating menopausal symptoms and other gynecological problems.[10][15] Meta-analyses of contemporary evidence support these claims on menopausal complaints only for products holding a marketing authorization for this indication,[4][5] whereas there is no high-quality scientific evidence to support such uses for other products.[12][8][16]

For authorized herbal medicinal products made from cimicifuga racemosa, some clinical study evidence shows supplemental beneficial effects on sleep disorders associated with hot flushes and profuse sweating attacks.[17][18]

A review published by Cochrane in 2012 was rather cautious with previous results and the efficacy of Cimicifuga preparations for menopausal symptoms.[16] The Cochrane review included and compared  preparations of greatly varying qualities (namely tested medicinal products, products without marketing approval as well as dietary supplements); the indications for use also varied. Additionally, studies were included that were conducted with products from unidentified black cohosh varieties. At the same time, several published studies were not even considered or were excluded without justification.[19]

Exhaustive meta-analyses have proven the efficacy of Cimicifuga medicinal products for menopausal symptoms, in particular those with an isopropanolic extract.[19] A review from 2013 was the first to include all full publications from 2000-2012 and differentiate between the Cimicifuga preparations by type of extract, status, and indication.[4] According to this review, only standardized, tested, and approved medicinal products could provide evidence (rational phytotherapy) and a positive risk-benefit profile.[4] More recent studies with an ethanolic extract also demonstrated a positive impact on medium- and long-term menopausal effects such as weight gain and metabolic disorders.[20][21] 

Medicinal products that contain an isopropanolic Cimicifuga extract are also suitable for patients who suffer from menopausal symptoms after breast cancer therapy, the women only need to talk to their attending physician first.[22][23] Relapse-free survival is not impaired; if anything, Cimicifuga may likely promote relapse-free survival.[24]

Safety and health concerns

The Herbal Medicinal Product Committee (HMPC) at the European Medicines Agency (EMA) has summarized the adverse drug reactions of herbal medicines made from cimicifuga with mentioning allergic skin reactions (urticaria, itching, exanthema), facial oedema and peripheral oedema, and gastrointestinal symptoms (i.e. dyspeptic disorders, diarrhoea).[3]

Studies on the long-term safety of using herbal medicines made from black cohosh are available. They do not show harmful effects on breast tissue,[25][26] endometrium[27][28][29][30] or breast cancer survivors.[24] In contrast, such studies have not been published for dietary supplements made from black cohosh.[2][12][8] Most black cohosh materials are harvested from the wild. Lack of proper authentication and adulteration of commercial preparations by other plant species are risk factors in dietary supplements[10][31] and a critical matter of quality control in herbal medicinal products holding a marketing authorization. Very high doses of black cohosh may cause nausea, dizziness, visual effects, a lower heart rate, and increased perspiration.[12]

Worldwide, some 83 cases of liver damage, including hepatitis, liver failure, and elevated liver enzymes, have been associated with using black cohosh, although a cause-and-effect relationship remains undefined.[2] Millions of women have taken black cohosh without reporting adverse health effects,[8] and a meta-analysis of clinical trials found no evidence that black cohosh preparations had adverse effects on liver function.[32] Package leaflets of phytomedicines made from black cohosh caution that people with liver problems should not take it,[8][33] although a 2011 meta-analysis of research evidence suggested this concern may be unfounded.[32] In 2007, the Australian Government warned that black cohosh may cause liver damage, although rarely, and should not be used without medical supervision.[34] Other studies concluded that liver damage from use of black cohosh is unlikely.[35][36][37] The clinical picture is similar to an autoimmune hepatitis with centrilobular liver cell necrosis, which can be treated with corticosteroids.[38]

Phytochemicals and pharmacology

The rhizomes and roots of black cohosh (cimicifuga racemosa rhizoma) contain diverse phytochemicals, particularly various saponins (triterpene saponins/triterpene glycosides such as actein) as well as cimifugic acids and other phenol carboxylic acids.[3][14][39][40] The pharmacologically active substance comprises the total extract.[3] In the past, estrogen-like properties were attributed to preparations from this herbal drug. However, formonetin —a phytoestrogen compound (isoflavone)— could only be detected in methanolic extracts[41] and was not found in ethanolic or isopropanolic cimicifuga extracts.[42] Today, an estrogen-like mechanism of action can be ruled out.[43][44] Regarding the alleviation of menopausal symptoms, central nervous activity was suspected as early as 2003,[45] and it has since been confirmed with preclinical and clinical data.[29][46]

See also

References

  1. ^ "International Plant Names Index". www.ipni.org.
  2. ^ a b c d e "Black cohosh: Fact sheet for health professionals". Office of Dietary Supplements, US National Institutes of Health. 30 August 2018. Retrieved 14 February 2019.
  3. ^ a b c d e f g Herbal Medicinal Product Committee (HMPC) at the European Medicines Agency (EMA) (2018-03-27). "Assessment report on Cimicifuga racemosa (L.) Nutt., rhizoma" (PDF).
  4. ^ a b c d Beer, A.-M.; Neff, A. (2013). "Differentiated Evaluation of Extract-Specific Evidence on Cimicifuga racemosa 's Efficacy and Safety for Climacteric Complaints". Evidence-Based Complementary and Alternative Medicine. 2013: 1–21. doi:10.1155/2013/860602. ISSN 1741-427X. PMC 3767045. PMID 24062793.
  5. ^ a b Castelo-Branco, C.; Gambacciani, M.; Cano, A.; Minkin, M. J.; Rachoń, D.; Ruan, X.; Beer, A.-M.; Schnitker, J.; Henneicke-von Zepelin, H.-H.; Pickartz, S. (2021-03-04). "Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms – an update on the evidence". Climacteric. 24 (2): 109–119. doi:10.1080/13697137.2020.1820477. ISSN 1369-7137.
  6. ^ Henneicke-von Zepelin, Hans-Heinrich (2017). "60 years of Cimicifuga racemosa medicinal products: Clinical research milestones, current study findings and current development". Wiener Medizinische Wochenschrift. 167 (7–8): 147–159. doi:10.1007/s10354-016-0537-z. ISSN 0043-5341. PMC 5409920. PMID 28155126.
  7. ^ a b c Compton JA, Culham A, Jury SL (1998). "Reclassification of Actaea to include Cimicifuga and Souliea (Ranunculaceae): Phylogeny inferred from morphology, nrDNA ITS, and epDNA trnL-F sequence variation". Taxon. 47 (3): 593–634. doi:10.2307/1223580. JSTOR 1223580.
  8. ^ a b c d e "Black cohosh". National Center for Complementary and Integrative Health, US National Institutes of Health. 1 September 2016. Retrieved 14 February 2019.
  9. ^ a b Richo Cech (2002). Growing at-risk medicinal herbs. Horizon Herbs. pp. 10–27. ISBN 0-9700312-1-1.
  10. ^ a b c d Predny ML, De Angelis P, Chamberlain JL (2006). "Black cohosh (Actaea racemosa): An annotated Bibliography". General Technical Report SRS–97. Department of Agriculture Forest Service, Southern Research Station: 99. Retrieved 2009-08-24.
  11. ^ "Actaea racemosa". Royal Horticultural Society. Retrieved 5 March 2020.
  12. ^ a b c d "Black cohosh". Drugs.com. 7 June 2018. Retrieved 14 February 2019.
  13. ^ Niering, William A.; Olmstead, Nancy C. (1985) [1979]. The Audubon Society Field Guide to North American Wildflowers, Eastern Region. Knopf. p. 732. ISBN 0-394-50432-1.
  14. ^ a b Wende, Kristian; Mügge, Clemens; Thurow, Kerstin; Schöpke, Thomas; Lindequist, Ulrike (2001-07-01). "Actaeaepoxide 3- O -β- d -Xylopyranoside, a New Cycloartane Glycoside from the Rhizomes of Actaea r acemosa ( Cimicifuga r acemosa )". Journal of Natural Products. 64 (7): 986–989. doi:10.1021/np000619e. ISSN 0163-3864.
  15. ^ Geller, Stacie E.; Studee, Laura (1 November 2006). "Contemporary Alternatives to Plant Estrogens for Menopause". Maturitas. 55 (Suppl 1): S3–13. doi:10.1016/j.maturitas.2006.06.012. ISSN 0378-5122. PMC 1780040. PMID 16884867.
  16. ^ a b Leach, MJ; Moore, V (12 September 2012). "Black cohosh (Cimicifuga spp.) for menopausal symptoms". The Cochrane Database of Systematic Reviews. 9 (9): CD007244. doi:10.1002/14651858.CD007244.pub2. PMC 6599854. PMID 22972105.
  17. ^ Osmers, Ruediger; Friede, Michael; Liske, Eckehard; Schnitker, Joerg; Freudenstein, Johannes; Henneicke-von Zepelin, Hans-Heinrich (2005). "Efficacy and Safety of Isopropanolic Black Cohosh Extract for Climacteric Symptoms:". Obstetrics & Gynecology. 105 (5, Part 1): 1074–1083. doi:10.1097/01.AOG.0000158865.98070.89. ISSN 0029-7844.
  18. ^ Jiang, K.; Jin, Y.; Huang, L.; Feng, S.; Hou, X.; Du, B.; Zheng, J.; Li, L. (2015-07-04). "Black cohosh improves objective sleep in postmenopausal women with sleep disturbance". Climacteric. 18 (4): 559–567. doi:10.3109/13697137.2015.1042450. ISSN 1369-7137.
  19. ^ a b Beer, André-M.; Osmers, Rüdiger; Schnitker, Jörg; Bai, Wenpei; Mueck, Alfred O.; Meden, Harald (2013). "Efficacy of black cohosh ( Cimicifuga racemosa ) medicines for treatment of menopausal symptoms – comments on major statements of the Cochrane Collaboration report 2012 "black cohosh ( Cimicifuga spp.) for menopausal symptoms (review)"". Gynecological Endocrinology. 29 (12): 1022–1025. doi:10.3109/09513590.2013.831836. ISSN 0951-3590.
  20. ^ Lena Friederichsen et al.: Effect of CIMicifuga racemosa on metaBOLIC parameters in women with menopausal symptoms: A retrospective observational study (CIMBOLIC). Archives of Gynecology and Obstetrics, Ausgabe 2/2020. doi:10.1007/s00404-019-05366-8
  21. ^ C. Moser et al.: Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice. Phytomedicine Volume 21, Issue 11, 25. September 2014, S. 1382-1389. doi:10.1016/j.phymed.2014.06.002
  22. ^ X. Ruan, A. O. Mueck, A.-M. Beer, B. Naser, S. Pickartz (2019-07-04), "Benefit–risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John's wort in breast cancer patients", Climacteric (in German), 22 (4), pp. 339–347, doi:10.1080/13697137.2018.1551346, ISSN 1369-7137, PMID 30626212CS1 maint: multiple names: authors list (link)
  23. ^ Herbal Medicinal Product Committee (HMPC) at the European Medicines Agency (EMA) (2018-03-27). "Assessment report on Cimicifuga racemosa (L.) Nutt., rhizoma" (PDF).
  24. ^ a b H.H. Henneicke-von Zepelin, H. Meden, K. Kostev, D. Schröder-Bernhardi, U. Stammwitz (2007-03-01), "Isopropanolic black cohosh extract and recurrence-free survival after breast cancer", Int. Journal of Clinical Pharmacology and Therapeutics (in German), 45 (03), pp. 143–154, doi:10.5414/CPP45143, ISSN 0946-1965CS1 maint: multiple names: authors list (link)
  25. ^ Hirschberg, Angelica Lindén; Edlund, Måns; Svane, Gunilla; Azavedo, Edward; Skoog, Lambert; von Schoultz, Bo (2007). "An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women". Menopause. 14 (1): 89–96. doi:10.1097/01.gme.0000230346.20992.34. ISSN 1072-3714.
  26. ^ Lundström, E.; Hirschberg, A.L.; Söderqvist, G. (2011). "Digitized assessment of mammographic breast density – Effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo". Maturitas. 70 (4): 361–364. doi:10.1016/j.maturitas.2011.08.009.
  27. ^ Bai, Wenpei; Henneicke-von Zepelin, Hans-Heinrich; Wang, Shuyu; Zheng, Shurong; Liu, Jianli; Zhang, Zhonglan; Geng, Li; Hu, Lina; Chunfeng, Jiao; Liske, Eckehard (2007). "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. 58 (1): 31–41. doi:10.1016/j.maturitas.2007.04.009.
  28. ^ Rauš, Karel; Brucker, Cosima; Gorkow, Christoph; Wuttke, Wolfgang (2006). "First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055". Menopause. 13 (4): 678–691. doi:10.1097/01.gme.0000196813.34247.e2. ISSN 1072-3714.
  29. ^ a b Hans-Heinrich Henneicke-von Zepelin (May 2017), "60 years of Cimicifuga racemosa medicinal products: Clinical research milestones, current study findings and current development", Wiener Medizinische Wochenschrift (in German), 167 (7–8), pp. 147–159, doi:10.1007/s10354-016-0537-z, ISSN 0043-5341, PMC 5409920, PMID 28155126
  30. ^ Herbal Medicinal Product Committee (HMPC) at the European Medicines Agency (EMA) (2018-03-27). "Assessment report on Cimicifuga racemosa (L.) Nutt., rhizoma" (PDF).
  31. ^ Teschke R, Schmidt-Taenzer W, Wolff A (2011). "Herb induced liver injury presumably caused by black cohosh: a survey of initially purported cases and herbal quality specifications" (PDF). Annals of Hepatology. 10 (3): 249–59. doi:10.1016/S1665-2681(19)31536-4. PMID 21677326.
  32. ^ a b Naser, Belal; Schnitker, Jörg; Minkin, Mary Jane; De Arriba, Susana Garcia; Nolte, Klaus-Ulrich; Osmers, Rüdiger (2011). "Suspected black cohosh hepatotoxicity". Menopause. 18 (4): 366–75. doi:10.1097/gme.0b013e3181fcb2a6. PMID 21228727. S2CID 6221776.
  33. ^ "Black Cohosh". Cancer Research UK. Retrieved 13 October 2016.
  34. ^ "Black cohosh (Cimicifuga racemosa): New labelling requirements and consumer information for medicines containing Black cohosh". Therapeutic Goods Administration, Department of Health, Australian Government. 29 May 2007. Retrieved 14 February 2019.
  35. ^ Teschke R, Schmidt-Taenzer W, Wolff A (2011). "Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: is the liver-unspecific Naranjo scale precise enough to ascertain causality?". Pharmacoepidemiology and Drug Safety. 20 (6): 567–82. doi:10.1002/pds.2127. PMID 21702069. S2CID 23801005.
  36. ^ Rolf Teschke (2010), "Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review", Menopause (in German), 17 (2), pp. 426–440, doi:10.1097/gme.0b013e3181c5159c, ISSN 1072-3714
  37. ^ Belal Naser, Jörg Schnitker, Mary Jane Minkin, Susana Garcia de Arriba, Klaus-Ulrich Nolte (2011), "Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract", Menopause (in German), 18 (4), pp. 366–375, doi:10.1097/gme.0b013e3181fcb2a6, ISSN 1072-3714CS1 maint: multiple names: authors list (link)
  38. ^ Grace Guzman, Eric R. Kallwitz, Christina Wojewoda, Rohini Chennuri, Jamie Berkes, Thomas J. Layden, Scott J. Cotler (2009), "Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh", Case Reports in Medicine (in German), 2009 (Article ID 918156), pp. 1–8, doi:10.1155/2009/918156, PMC 2814377, PMID 20130783CS1 maint: multiple names: authors list (link) CS1 maint: date and year (link)
  39. ^ Viereck V, Emons G, Wuttke W (2005). "Black cohosh: just another phytoestrogen?". Trends in Endocrinology and Metabolism. 16 (5): 214–221. doi:10.1016/j.tem.2005.05.002. PMID 15927480. S2CID 156791.
  40. ^ Nuntanakorn P, Jiang B, Yang H, Cervantes-Cervantes M, Kronenberg F, Kennelly EJ (2007). "Analysis of polyphenolic compounds and radical scavenging activity of four American Actaea species". Phytochem Anal. 18 (3): 219–28. doi:10.1002/pca.975. PMC 2981772. PMID 17500365.
  41. ^ Hussein Al-Amier et al.: Evaluation of Extraction Methods for Isolation and Detection of Formononetin in Black Cohosh (Actaea racemosa L.). Journal of Medicinally Active Plants (1):6-12. doi:10.7275/R5CR5R84
  42. ^ E.J. Kennelly, S. Baggett, P. Nuntanakorn, A.L. Ososki, S.A. Mori (January 2002), "Analysis of thirteen populations of Black Cohosh for formononetin", Phytomedicine (in German), 9 (5), pp. 461–467, doi:10.1078/09447110260571733CS1 maint: multiple names: authors list (link)
  43. ^ Heidi Fritz et al.: Black cohosh and breast cancer: A systematic review. Integr Cancer Ther. 2014 Jan;13(1):12-29. doi:10.1177/1534735413477191
  44. ^ Marcela Garita-Hernandez et al.: The growth inhibitory activity of the Cimicifuga racemosa extract Ze 450 is mediated through estrogen and progesterone receptors-independent pathways. Planta Med. 2006 Mar;72(4):317-23. doi:10.1055/s-2005-916233
  45. ^ F. Borrelli et al.: Pharmacological effects of Cimicifuga racemosa. Life Sci. 2003 Jul 25;73(10):1215-29. doi:10.1016/s0024-3205(03)00378-3
  46. ^ Petra Stute, Stefan Ehrentraut, Hans-Heinrich Henneicke-von Zepelin, Petra Nicken (2021-07-14), "Gene expression analyses on multi-target mode of action of black cohosh in menopausal complaints – a pilot study in rodents", Archives of Gynecology and Obstetrics (in German), doi:10.1007/s00404-021-06105-8, ISSN 0932-0067CS1 maint: multiple names: authors list (link)
  47. ^ a b Murray, edited by Joseph E. Pizzorno Jr., Michael T. (2012). Textbook of natural medicine (4th ed.). Edinburgh: Churchill Livingstone. p. 661. ISBN 9781437723335.CS1 maint: extra text: authors list (link)