Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Pharmacognosy of Black Cohosh: The Phytochemical and Biological Profile of a Major Botanical Dietary Supplement

  • Chapter
  • First Online:
Progress in the Chemistry of Organic Natural Products 99

Part of the book series: Progress in the Chemistry of Organic Natural Products ((POGRCHEM,volume 99))

Abstract

The ethnobotanical, Black Cohosh, a preparation from the roots/rhizomes of Actaea racemosa, has been the subject of extensive investigations. Despite the fact that sales figures place it among the top ten U.S. dietary supplements, the mechanisms of its amelioration of the adverse effects of menstruation and menopause remain largely undefined. The plant is a prodigious “factory” of complex secondary metabolites, with almost 50 cycloartane triterpenes, over 70 alkaloids, and 11 phenolic acids characterized so far, and this chapter discusses the chemistry of the A. racemosa secondary metabolome in detail. While numerous in vitro and in vivo pharmacological and biological studies attribute diverse specific biochemical effects to individual metabolites or defined extracts, an adequate explanation of potencies and drug(-like) concentrations is still lacking. As many of the effects may play a role in the alleviation of menopausal symptoms, the possibility exists that the overall effect may be the result of a combination of both multiple bioactive principles and several synergistic interactions. On careful analysis, a purported hepatotoxicity risk raised has been relegated to “a possible rare idiosyncratic reaction”. More than 50 clinical studies defy definitive analysis, other than confirming that the material is safe, in part because of poor study design and differences in preparations used. The global literature on Black Cohosh is almost unanimous in a call for larger, more well-designed clinical studies, and recent advances in the understanding of the phytoconstituents justify a more thorough secondary metabolomics analysis of this interesting North American plant.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    An attempt to ascertain authentication resulted in a letter from the Chinese supplier stating that this was Black Cohosh (personal communication from one of the authors).

  2. 2.

    It should be noted that Cimicifuga Rhizoma is not produced from A. racemosa.

References

  1. Moermann DE (1986) Medicinal Plants of Native America. Museum of Anthropology, University of Michigan, Ann Arbor, Michigan, USA

    Google Scholar 

  2. Anonymous 1820, The Pharmacopœia of the United States of America (the United States Pharmacopœia) 1820-19, Easton, Pennsylvania, USA

    Google Scholar 

  3. Blumenthal M, Lindstrom A, Ooyen C, Lynch ME (2012) Herb Supplement Sales Increase 4.5% in 2011. HerbalGram 95:60

    Google Scholar 

  4. Foster S (2013) Exploring the Peripatetic Maze of Black Cohosh Adulteration - a Review of the Nomenclature, Distribution, Chemistry, Market Status, Analytical Methods and Safety Concerns of This Popular Herb. HerbalGram 98:32

    Google Scholar 

  5. Li JX, Yu ZY (2006) Cimicifugae Rhizoma: From Origins, Bioactive Constituents to Clinical Outcomes. Curr Med Chem 13:2927

    CAS  Google Scholar 

  6. Imai A, Yao P, Overk C, Bolton JL, Nikolic D, van Breemen RB, Pauli GF (2008) Phytochemical Investigation of the Estrogenic Aerial Parts of Cimicifuga racemosa (L.) Nutt. (Ranunculaceae), 2008 Interim ASP and Oxford ISCB Meeting, Oxford, Mississippi, USA

    Google Scholar 

  7. Mimaki Y, Nadaoka I, Yasne M, Ohtake Y, Ikeda M, Watanabe K, Sashida Y (2006) Neocimicigenosides A and B, Cycloartane Glycosides from the Rhizomes of Cimicifuga racemosa and Their Effects on CRF-Stimulated ACTH Secretion from AtT-20 Cells. J Nat Prod 69:829

    CAS  Google Scholar 

  8. Qiu F, Imai A, McAlpine J, Lankin DC, Burton IW, Karakach TK, Farnsworth NR, Pauli GF (2012) Dereplication, Residual Complexity and Rational Naming – the Case of the Actaea Triterpenes. J Nat Prod 75:432

    CAS  Google Scholar 

  9. Friesen JB, Pauli GF (2005) G.U.E.S.S. - a Generally Useful Estimate of Solvent Systems. J Liq Chromatogr Relat Technol 28:2877

    Google Scholar 

  10. Chen S-N, Fabricant DS, Lu Z-Z, Fong HHS, Farnsworth NR (2002) Cimiracemosides I-P, New 9,19-Cyclolanostane Triterpene Glycosides from Cimicifuga racemosa. J Nat Prod 65:1391

    CAS  Google Scholar 

  11. Cicek SS, Schwaiger S, Ellmerer E, Stuppner H (2010) Development of a Fast and Convenient Method for the Isolation of Triterpene Saponins from Actaea racemosa by High-Speed Countercurrent Chromatography Coupled with Evaporative Light Scattering Detection. Planta Med 76:467

    CAS  Google Scholar 

  12. Friesen JB, Pauli GF (2007) Rational Development of Solvent System Families in Counter-Current Chromatography. J Chromatogr A 1151:51

    CAS  Google Scholar 

  13. Zhou L, Yang JS, Tu GZ, Zou JH (2006) Cyclolanostane Triterpene Glycosides from Souliea vaginata. Chem Pharm Bull 54:823

    CAS  Google Scholar 

  14. Chen S-N, Lankin DC, Nikolic D, Fabricant DS, Lu ZZ, Ramirez B, van Breemen RB, Fong HHS, Farnsworth NR, Pauli GF (2007) Chlorination Diversifies Cimicifuga racemosa Triterpene Glycosides. J Nat Prod 70:1016

    CAS  Google Scholar 

  15. Napolitano J, Lankin DC, Graf TN, Friesen JB, Chen S-N, McAlpine J, Oberlies NH, Pauli GF (2013) HiFSA Fingerprinting of Isomers with Near Identical NMR Spectra: The Silybin/Isosilybin Case. J Org Chem 78:2827

    CAS  Google Scholar 

  16. Napolitano JG, Gödecke T, Rodriguez Brasco MF, Jaki BU, Chen S-N, Lankin DC, Pauli GF (2012) The Tandem of Full Spin Analysis and QHNMR for the Quality Control of Botanicals Exemplified with Ginkgo biloba. J Nat Prod 75:238

    CAS  Google Scholar 

  17. Inokuma Y, Yoshioka S, Ariyoshi J, Arai T, Hitora Y, Takada K, Matsunaga S, Rissanen K, Fujita M (2013) X-Ray Analysis on the Nanogram to Microgram Scale Using Porous Complexes. Nature 495:461

    CAS  Google Scholar 

  18. Chen S-N, Li W, Fabricant DS, Santarsiero BD, Mesecar AD, Fitzloff JF, Fong HHS, Farnsworth NR (2002) Isolation, Structure Elucidation, and Absolute Configuration of 26-Deoxyactein from Cimicifuga racemosa and Clarification of Nomenclature Associated with 27-Deoxyactein. J Nat Prod 65:601

    Google Scholar 

  19. He K, Zheng BL, Kim CH, Rogers L, Zheng QY (2000) Direct Analysis and Identification of Triterpene Glycosides by LC/MS in Black Cohosh, Cimicifuga racemosa, and in Several Commercially Available Black Cohosh Products. Planta Med 66:635

    CAS  Google Scholar 

  20. Avula B, Wang YH, Smillie TJ, Khan IA (2009) Quantitative Determination of Triterpenoids and Formononetin in Rhizomes of Black Cohosh (Actaea racemosa) and Dietary Supplements by Using UPLC-UV/ELS Detection and Identification by UPLC-MS. Planta Med 75:381

    CAS  Google Scholar 

  21. Gödecke T, Napolitano JG, Rodriguez Brasco MF, Chen S-N, Jaki BU, Lankin DC, Pauli GF (2013) Validation of a Generic QHNMR Method for Natural Products Analysis. Phytochem Anal 24:581

    Google Scholar 

  22. Pauli GF, Jaki BU, Gödecke T, Lankin DC (2012) Quantitative 1H NMR: Development and Potential of a Method for Natural Products Analysis - an Update. J Nat Prod 75:834

    CAS  Google Scholar 

  23. Pauli GF, Jaki BU, Lankin DC (2005) Quantitative 1H NNMR: Development and Potential of a Method for Natural Products Analysis. J Nat Prod 68:133

    CAS  Google Scholar 

  24. Gödecke T, Nikolic D, Lankin DC, Chen S-N, Powell SL, Dietz B, Bolton JL, van Breemen RB, Farnsworth NR, Pauli GF (2009) Phytochemistry of Cimicifugic Acids and Associated Bases in Black Cohosh Root Extracts. Phytochem Anal 20:120

    Google Scholar 

  25. Kruse SO, Löhning A, Pauli GF, Winterhoff H, Nahrstedt A (1999) Fukiic and Piscidic Acid Esters from the Rhizome of Cimicifuga racemosa and the Estrogenic Activity of Fukinolic Acid. Planta Med 65:763

    CAS  Google Scholar 

  26. Finnemore H (1909) Constituents of Rhizome of Cimicifuga racemosa. Pharm J 83:145

    CAS  Google Scholar 

  27. Gemeinhardt K, Sade H, Schenck G (1956) Beiträge zu Einem Ergänzungsbuch für das Homöopathische Arzneibuch. 3. Mitteilung: Cimicifuga racemosa (L.) Nutt. Pharm Z 101:238

    Google Scholar 

  28. Swain T (1966) Comparative Phytochemistry. Academic Press, London, New York, p xiii

    Google Scholar 

  29. Laidlaw PP (1912) Laburnum Poisoning and Cytisine. Proc Royal Soc Med 5:10

    CAS  Google Scholar 

  30. Crum JD, Cassady JM, Olmstead PM, Picha NJ (1965) The Chemistry of Alkaloids. I. The Screening of Some Native Ohio Plants. Proc West Virginia Acad Sci 37:143

    CAS  Google Scholar 

  31. Furgiuele AR, Farnsworth NR, Buckley JP (1962) False-Positive Alkaloid Reactions Obtained with Extracts of Piper methysticum. J Pharm Sci 51:1156

    CAS  Google Scholar 

  32. Fabricant D, Nikolic D, Lankin DC, Chen S-N, Jaki B, Krunic A, van Breemen RB, Fong HHS, Farnsworth NR, Pauli GF (2005) Cimipronidine: A Novel Cyclic Guanidine Alkaloid from Cimicifuga racemosa (L.) Nutt. J Nat Prod 68:1266

    CAS  Google Scholar 

  33. Powell SL, Gödecke T, Nikolic D, Chen S-N, Dietz B, Farnsworth NR, van Breemen RB, Lankin DC, Pauli GF, Bolton JL (2008) In Vitro Serotonergic Activity of Black Cohosh and Identification of Nω-Methylserotonin as Active Constituent. J Agric Food Chem 56:11718

    CAS  Google Scholar 

  34. Gödecke T, Lankin DC, Nikolic D, Chen S-N, van Breemen RB, Farnsworth NR, Pauli GF (2009) Guanidine Alkaloids and Pictet-Spengler Adducts from Black Cohosh (Cimicifuga racemosa). J Nat Prod 72:433

    Google Scholar 

  35. Nikolić D, Gödecke T, Chen S-N, White J, Lankin DC, Pauli GF, van Breemen RB (2012) Mass Spectrometric Dereplication of Nitrogen-Containing Constituents of Black Cohosh (Cimicifuga racemosa L.). Fitoterapia 83:441

    Google Scholar 

  36. Stevigny C, Bailly C, Quetin-Leclercq J (2005) Cytotoxic and Antitumor Potentialities of Aporphinoid Alkaloids. Curr Med Chem Anticancer Agents 5:173

    CAS  Google Scholar 

  37. Wood KV, Bonham CC, Miles D, Rothwell AP, Peel G, Wood BC, Rhodes D (2002) Characterization of Betaines Using Electrospray MS/MS. Phytochemistry 59:759

    CAS  Google Scholar 

  38. Morin AM (1984) Beta-Carboline Kindling of the Benzodiazepine Receptor. Brain Res 321:151

    CAS  Google Scholar 

  39. Lippke KP, Schunack WG, Wenning W, Muller WE (1983) Beta-Carbolines as Benzodiazepine Receptor Ligands. 1. Synthesis and Benzodiazepine Receptor Interaction of Esters of Beta-Carboline-3-Carboxylic Acid. J Med Chem 26:499

    CAS  Google Scholar 

  40. Hagen TJ, Skolnick P, Cook JM (1987) Synthesis of 6-Substituted Beta-Carbolines that Behave as Benzodiazepine Receptor Antagonists or Inverse Agonists. J Med Chem 30:750

    CAS  Google Scholar 

  41. Ishida J, Wang HK, Bastow KF, Hu CQ, Lee KH (1999) Antitumor Agents 201. Cytotoxicity of Harmine and Beta-Carboline Analogs. Bioorg Med Chem Lett 9:3319

    CAS  Google Scholar 

  42. Xu Z, Chang FR, Wang HK, Kashiwada Y, McPhail AT, Bastow KF, Tachibana Y, Cosentino M, Lee KH (2000) Anti-HIV Agents 45 (1) and Antitumor Agents 205 (2). Two New Sesquiterpenes, Leitneridanins A and B, and the Cytotoxic and Anti-HIV Principles from Leitneria floridana. J Nat Prod 63:1712

    CAS  Google Scholar 

  43. Tsuda M, Watanabe D, Kobayashi J (1998) Maeganedin A, a New Manzamine Alkaloid from Amphimedon Sponge. Tetrahedron Lett 39:1207

    CAS  Google Scholar 

  44. Di Giorgio C, Delmas F, Ollivier E, Elias R, Balansard G, Timon-David P (2004) In Vitro Activity of the Beta-Carboline Alkaloids Harmane, Harmine, and Harmaline toward Parasites of the Species Leishmania infantum. Exp Parasitol 106:67

    Google Scholar 

  45. Da Cunha EV, Fechinei IM, Guedes DN, Barbosa-Filho JM, Da Silva MS (2005) Protoberberine Alkaloids. Alkaloids Chem Biol 62:1

    Google Scholar 

  46. Grycova L, Dostal J, Marek R (2007) Quaternary Protoberberine Alkaloids. Phytochemistry 68:150

    CAS  Google Scholar 

  47. Schmidt J, Boettcher C, Kuhnt C, Kutchan TM, Zenk MH (2007) Poppy Alkaloid Profiling by Electrospray Tandem Mass Spectrometry and Electrospray FT-ICR Mass Spectrometry after [Ring-13C6]-Tyramine Feeding. Phytochemistry 68:189

    CAS  Google Scholar 

  48. Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA, Fan TWM, Fiehn O, Goodacre R, Griffin JL, Hankemeier T, Hardy N, Harnly J, Higashi R, Kopka J, Lane AN, Lindon JC, Marriott P, Nicholls AW, Reily MD, Thaden JJ, Viant MR (2007) Proposed Minimum Reporting Standards for Chemical Analysis. Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 3:211

    CAS  Google Scholar 

  49. Dookeran NN, Yalcin T, Harrison AG (1996) Fragmentation Reactions of Protonated α-Amino Acids. J Mass Spectrom 31:500

    CAS  Google Scholar 

  50. Kuhnert N, Jaiswal R, Matei MF, Sovdat T, Deshpande S (2010) How to Distinguish between Feruloyl Quinic Acids and Isoferuloyl Quinic Acids by Liquid Chromatography/Tandem Mass Spectrometry. Rapid Commun Mass Spectrom 24:1575

    CAS  Google Scholar 

  51. Somei M, Teranishi S, Yamada K, Yamada F (2001) The Chemistry of Indoles. CVII. A Novel Synthesis of 3,4,5,6-Tetrahydro-7-hydroxy-1H-azepino[5,4,3-cd]indoles and a New Finding on Pictet-Spengler Reaction. Chem Pharm Bull 49:1159

    CAS  Google Scholar 

  52. Facchini PJ (2001) Alkaloid Biosynthesis in Plants: Biochemistry, Cell Biology, Molecular Regulation, and Metabolic Engineering Applications. Ann Rev Plant Physiol Plant Mol Biol 52:29

    CAS  Google Scholar 

  53. Stevigny C, Jiwan JL, Rozenberg R, de Hoffmann E, Quetin-Leclercq J (2004) Key Fragmentation Patterns of Aporphine Alkaloids by Electrospray Ionization with Multistage Mass Spectrometry. Rapid Commun Mass Spectrom 18:523

    CAS  Google Scholar 

  54. Zhang Y, Shi Q, Shi P, Zhang W, Cheng Y (2006) Characterization of Isoquinoline Alkaloids, Diterpenoids and Steroids in the Chinese Herb Jin-Guo-Lan (Tinospora sagittata and Tinospora capillipes) by High-Performance Liquid Chromatography/Electrospray Ionization with Multistage Mass Spectrometry. Rapid Commun Mass Spectrom 20:2328

    CAS  Google Scholar 

  55. Henion JD, Mordehai AV, Cai J (1994) Quantitative Capillary Electrophoresis-Ion Spray Mass Spectrometry on a Benchtop Ion Trap for the Determination of Isoquinoline Alkaloids. Anal Chem 66:2103

    CAS  Google Scholar 

  56. Guo Y, Kojima K, Lin L, Fu X, Zhao C, Hatano K, Chen Y-J, Ogihara Y (1999) A New N-Methyltetrahydroprotoberberine Alkaloid from Tinospora hainanesis. Chem Pharm Bull 47:287

    CAS  Google Scholar 

  57. Matsuda H, Suzuki Y (1984) γ-Guanidinobutyraldehyde Dehydrogenase of Vicia faba Leaves. Plant Physiol 76:654

    CAS  Google Scholar 

  58. Musshoff F, Lachenmeier DW, Schmidt P, Dettmeyer R, Madea B (2005) Systematic Regional Study of Dopamine, Norsalsolinol, and (R/S)-Salsolinol Levels in Human Brain Areas of Alcoholics. Alcohol Clin Exp Res 29:46

    CAS  Google Scholar 

  59. Reuter G, Diehl HJ (1971) Guanidine Derivatives in Leonurus sibiricus L. Pharmazie 26:777

    CAS  Google Scholar 

  60. Atta-ur-Rahman, Bhatti MK, Akhtar F, Choudhary MI (1992) Alkaloids of Fumaria indica. Phytochemistry 31:2869

    Google Scholar 

  61. Verbitski SM, Gourdin GT, Ikenouye LM, McChesney JD, Hildreth J (2008) Detection of Actaea racemosa Adulteration by Thin-Layer Chromatography and Combined Thin-Layer Chromatography-Bioluminescence. J AOAC Int 91:268

    CAS  Google Scholar 

  62. He K, Pauli GF, Zheng B, Wang H, Bai N, Peng T, Roller M, Zheng Q (2006) Cimicifuga Species Identification by High Performance Liquid Chromatography-Photodiode Array/Mass Spectrometric/Evaporative Light Scattering Detection for Quality Control of Black Cohosh Products. J Chromatogr A 1112:241

    CAS  Google Scholar 

  63. Jiang B, Ma C, Motley T, Kronenberg F, Kennelly EJ (2011) Phytochemical Fingerprinting to Thwart Black Cohosh Adulteration: A 15 Actaea Species Analysis. Phytochem Anal 22:339

    CAS  Google Scholar 

  64. Li W, Chen S, Fabricant D, Angerhofer CK, Fong HHS, Farnsworth NR, Fitzloff JF (2002) High-Performance Liquid Chromatographic Analysis of Black Cohosh (Cimicifuga racemosa) Constituents with in-Line Evaporative Light Scattering and Photodiode Array Detection. Anal Chim Acta 471:61

    CAS  Google Scholar 

  65. Jiang B, Kronenberg F, Nuntanakorn P, Qiu M-H, Kennelly EJ (2006) Evaluation of the Botanical Authenticity and Phytochemical Profile of Black Cohosh Products by High-Performance Liquid Chromatography with Selected Ion Monitoring Liquid Chromatography-Mass Spectrometry. J Agric Food Chem 54:3242

    CAS  Google Scholar 

  66. Avula B, Ali Z, Khan IA (2007) Chemical Fingerprinting of Actaea racemosa (Black Cohosh) and Its Comparison Study with Closely Related Actaea Species (A. pachypoda, A. podocarpa, A. rubra) by HPLC. Chromatographia 66:757

    CAS  Google Scholar 

  67. Jiang B, Kronenberg F, Balick MJ, Kennelly EJ (2006) Analysis of Formononetin from Black Cohosh (Actaea racemosa). Phytomedicine 13:477

    CAS  Google Scholar 

  68. Li W, Sun Y, Liang W, Fitzloff JF, van Breemen RB (2003) Identification of Caffeic Acid Derivatives in Actaea racemosa (Cimicifuga racemosa, Black Cohosh) by Liquid Chromatography/Tandem Mass Spectrometry. Rapid Commun Mass Spectrom 17:978

    CAS  Google Scholar 

  69. Zerega N, Mori S, Lindqvist C, Zheng Q, Motley T (2002) Using Amplified Fragment Length Polymorphisms (AFLP) to Identify Black Cohosh (Actaea racemosa). Econ Bot 65:164

    Google Scholar 

  70. Motley TJ, Lück L, Zerega NJC (2004) Genetic Diversity and DNA Fingerprinting of Black Cohosh (Actaea racemosa). Proc Global Summit Med Pl 1:112

    Google Scholar 

  71. Baker DA, Stevenson DW, Little DP (2012) DNA Barcode Identification of Black Cohosh Herbal Dietary Supplements. J AOAC Int 95:1023

    CAS  Google Scholar 

  72. Compton JA, Culham A, Jury SL (1998) Reclassification of Actaea to Include Cimicifuga and Souliea (Ranunculaceae): Phylogeny Inferred from Morphology, NRDNA, ITS, and CPDAN TRN-F Sequence Variation. Taxon 47:593

    Google Scholar 

  73. Jamróz MK, Jamróz MH, Dobrowolski JC, Gliński JA, Gleńsk M (2012) One New and Six Known Triterpene Xylosides from Cimicifuga racemosa: FT-IR, Raman and NMR Studies and DFT Calculations. Spectrochimica Acta Part A 93:10

    Google Scholar 

  74. Jamróz MK, Janróz MH, Dobrowolski JC, Glinski JA, Davey MH, Wawer I (2011) Novel and Unusual Triterpene from Black Cohosh. Determination of Structure of 9,10-Seco-9,19-Cyclolanostane Xyloside (Cimipodocarpaside) by NMR, IR and Raman Spectroscopy and DFT Calculations. Spectrochimica Acta, Part A 78:107

    Google Scholar 

  75. Jiang Y, David B, Tu P, Barbin Y (2010) Recent Analytical Approaches in Quality Control of Traditional Chinese Medicines - a Review. Anal Chim Acta 657:9

    CAS  Google Scholar 

  76. Bedir E, Khan IA (2000) Cimiracemoside A: A New Cyclolanostanol Xyloside from the Rhizome of Cimifuga racemosa. Chem Pharm Bull 48:425

    CAS  Google Scholar 

  77. Shao Y, Harris A, Wang MF, Zhang HJ, Cordell GA, Bowman M, Lemmo E (2000) Triterpene Glycosides from Cimicifuga racemosa. J Nat Prod 63:905

    CAS  Google Scholar 

  78. Kondo Y, Takemoto T (1972) The Structure of Cimifugin, a New Bitter Principle from Cimicifuga simplex Wormsk. Chem Pharm Bull 20:1940

    CAS  Google Scholar 

  79. Burdette JE, Liu J, Chen S-N, Fabricant DS, Piersen CE, Barker EL, Pezzuto JM, Mesecar AD, van Breemen RB, Farnsworth NR, Bolton JL (2003) Black Cohosh Acts as a Mixed Competitive Ligand and Partial Agonist of the Serotonin Receptor. J Agric Food Chem 51:5661

    CAS  Google Scholar 

  80. Liu JH, Burdette JE, Xu HY, Gu CG, van Breemen RB, Bhat KPL, Booth N, Constantinou AI, Pezzuto JM, Fong HHS, Farnsworth NR, Bolton JL (2001) Evaluation of Estrogenic Activity of Plant Extracts for the Potential Treatment of Menopausal Symptoms. J Agric Food Chem 49:2472

    CAS  Google Scholar 

  81. Einbond LS, Shimizu M, Ma H, Wu HA, Goldsberry S, Sicular S, Pnjikaran M, Genovese G, Cruz E (2008) Actein Inhibits the Na+-K+-ATPase and Enhances the Growth Inhibitory Effect of Digitoxin on Human Breast Cancer Cells. Biochem Biophys Res Commun 375:608

    CAS  Google Scholar 

  82. Jarry H, Harnischfeger G, Düker E-M (1985) Studies on the Endocrine Efficacy of the Constituents of Cimicifuga racemosa: 2. In Vitro Binding of Constituents to Estrogen Receptors. Planta Med 51:316

    CAS  Google Scholar 

  83. Kennelly EJ, Baggett S, Nuntanakorn P, Ososki AL, Mori SA, Duke J, Coleton M, Kronenberg F (2002) Analysis of Thirteen Populations of Black Cohosh for Formononetin. Phytomedicine 9:4161

    Google Scholar 

  84. Panossian A, Danielyan A, Mamikonyan G, Wikman G (2004) Methods of Phytochemical Standardisation of Rhizoma Cimicifugae Racemosae. Phytochem Anal 15:100

    CAS  Google Scholar 

  85. Seidlová-Wuttke D, Hesse O, Jarry H, Christoffel V, Spengler B, Becker T, Wuttke W (2003) Evidence for Selective Estrogen Receptor Modulator Activity in a Black Cohosh (Cimicifuga racemosa) Extract: Comparison with Estradiol-17β. Eur J Endocrinol 149:351

    Google Scholar 

  86. Qiu SX, Dan C, Ding LS, Peng S, Chen S-N, Farnsworth NR, Nolta J, Gross ML, Zhou P (2007) A Triterpene Glycoside from Black Cohosh That Inhibits Osteoclastogenesis by Modulating RANKL and TNRalpha Signaling Pathways. Chem Biol 14:860

    CAS  Google Scholar 

  87. Ruhlen RL, Sun GY, Sauter ER (2008) Black Cohosh: Insights into Its Mechanism(s) of Action. Integr Med Insights 2008:21

    Google Scholar 

  88. Kim CD, Lee W-K, Lee M-H, Cho HS, Lee YK, Roh S-S (2004) Inhibition of Mast Cell-Dependent Allergy Reaction by Extract of Black Cohosh (Cimicifuga racemosa). Immunopharmacol Immunotoxicol 26:299

    Google Scholar 

  89. Lee JH, Cuong TD, Kwack SJ, Seok JH, Lee JK, Jeong JY, Woo M-H, Choi JS, Lee HK, Min BS (2012) Cycloartane-Type Triterpene Glycosides from the Rhizomes of Cimicifuga heracleifolia and Their Anticomplementary Activity. Planta Med 78:1391

    CAS  Google Scholar 

  90. Burdette JE, Chen S-N, Lu ZZ, Xu H, White BE, Fabricant DS, Liu J, Fong HHS, Farnsworth NR, Constantinou AI, van Breemen RB, Pezzuto JM, Bolton JL (2002) Black Cohosh (Cimicifuga racemosa L.) Protects against Menadione-Induced DNA Damage through Scavenging of Reactive Oxygen Species: Bioassay-Directed Isolation and Characterization of Active Principles. J Agric Food Chem 50:7022

    CAS  Google Scholar 

  91. Einbond L, Saxe, Soffritti M, Esposti D, Degli, Park T, Cruz E, Su t, Wu H-A, Wang X, Zhang Y-J, Ham J, Goldberg IJ, Kronenberg F, Valdimirova A (2009) Actein Activates Stress- and Statin-Associated Responses and Is Bioavailable in Sprague-Dawley Rats. Fund Clin Pharmacol 23:311

    Google Scholar 

  92. Nadaoka I, Yasue M, Kitagawa Y, Koga Y (2012) Oral Administration of Cimicifuga racemosa Extract Attenuates Psychological and Physiological Stress Responses. Biomed Res 33:145

    CAS  Google Scholar 

  93. Nakazato K, Shimonaka Y (1982) The Japanese State-Trait Anxiety Inventory: Age and Sex Differences. Percept Motor Skills 69:611

    Google Scholar 

  94. Vitetta L, Thomsen M, Sali A (2003) Black Cohosh and Other Herbal Remedies Associated with Acute Hepatitis. Med J Aust 178:411

    Google Scholar 

  95. Lontos S, Jones RM, Angus PW, Gow PJ (2003) Acute Liver Failure Associated with the Use of Herbal Preparations Containing Black Cohosh. Med J Aust 179:390

    Google Scholar 

  96. Mahady GB, Low Dog T, Barrett ML, Chavez ML, Gardiner P, Ko R, Marles RJ, Pellicore LS, Giancaspro GI, Sarma DN (2008) United States Pharmacopeia Review of the Black Cohosh Case Reports of Hepatotoxicity. Menopause 15:628

    Google Scholar 

  97. Borrelli F, Ernst E (2008) Black Cohosh (Cimicifuga racemosa): A Systematic Review of Adverse Events. Am J Obstetr Gynecol 199:455

    Google Scholar 

  98. Roberts H (2010) Safety of Herbal Medicinal Products in Women with Breast Cancer. Maturitas 66:363

    Google Scholar 

  99. Teschke R, Schwarzenboeck A, Schmidt-Taenzer W, Wolff A, Hennermann KH (2011) Herb Induced Liver Injury Presumably Caused by Black Cohosh: A Survey of Initially Purported Cases and Herbal Quality Specifications. Ann Hepatol 10:249

    Google Scholar 

  100. Naser B, Schnitiker J, Minkin MJ, de Arriba SG, Noite K-U, Osmers R (2011) Suspected Black Cohosh Hepatotoxicity: No Evidence by Meta-Analysis of Randomized Controlled Clinical Trials for Isopropanolic Black Cohosh Extract. Menopause 18:366

    Google Scholar 

  101. Lüde S, Török M, Dieterle S, Knapp AC, Kaeufeler R, Jäggi R, Spornitz U, Krähenbühl S (2007) Hepatic Effects of Cimicifuga racemosa Extract in Vivo and in Vitro. Cell Mol Life Sci 64:2848

    Google Scholar 

  102. Mazzanti G, Di Sotto A, Franchitto A, Mastrangelo S, Pezzella M, Vitalone A, Mammola CL (2008) Effects of Cimicifuga racemosa Extracts on Liver Morphology and Hepatic Function Indices. Phytomedicine 15:1021

    CAS  Google Scholar 

  103. Campos LB, Gilglioni EH, Garcia R, Fernandes, Brito MdN, Natali MRM, Ishii-Iwamoto EL, Salgueiro-Pagadigorria CL (2012) Cimicifuga racemosa Impairs Fatty Acid Beta-Oxidation and Induces Oxidative Stress in Livers of Ovariectomized Rats with Renovascular Hypertension. Free Radical Biol Med 53:680

    Google Scholar 

  104. Fabricant DS, Farnsworth NR (2005) Black Cohosh (Cimicifuga racemosa), In: Coates P, Blackman M, Cragg G, Levine M, Moss J, White J (eds), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, p. 41

    Google Scholar 

  105. Liske E (1998) Therapeutic Efficacy and Safety of Cimicifuga racemosa for Gynecologic Disorders. Adv Ther 15:45

    CAS  Google Scholar 

  106. Huntley A, Ernst E (2003) A Systematic Review of the Safety of Black Cohosh. Menopause 10:58

    Google Scholar 

  107. Low Dog T, Powell KL, Weisman SM (2003) Critical Evaluation of the Safety of Cimicifuga racemosa in Menopause Symptom Relief. Menopause 10:299

    Google Scholar 

  108. Huntley A (2004) The Safety of Black Cohosh (Actaea racemosa, Cimicifuga racemosa). Expert Opin Drug Safety 3:615

    Google Scholar 

  109. Cohen SM, O’Connor AM, Hart J, Merel NH, Te HS (2004) Autoimmune Hepatitis Associated with the Use of Black Cohosh: A Case Study. Menopause 11:575

    Google Scholar 

  110. Joy D, Joy J, Duane P (2008) Black Cohosh: A Cause of Abnormal Postmenopausal Liver Function Tests. Climacteric 11:84

    CAS  Google Scholar 

  111. Chow ECY, Teo M, Ring JA, Chen JW (2008) Liver Failure Associated with the Use of Black Cohosh for Menopausal Symptoms. Med J Aust 188:420

    Google Scholar 

  112. Teschke R, Schwarzenboeck A (2009) Suspected Hepatotoxicity by Cimicifugae Racemosae Rhizoma (Black Cohosh, Root): Critical Analysis and Structured Causality Assessment. Phytomedicine 16:72

    Google Scholar 

  113. Teschke R, Bahre R, Genthner A, Fuchs J, Schmidt-Taenzer W, Wolff A (2009) Reply To: Suspected Black Cohosh Hepatotoxicity - Causality Assessment Versus Safety Signal. Quality Versus Quantity. Maturitas 64:141

    Google Scholar 

  114. Mahady G, Low Dog T, Sarma DN, Giancaspro GI (2009) Suspected Black Cohosh Hepatotoxicity - Causality Assessment Versus Safety Signal. Maturitas 64:139

    Google Scholar 

  115. Teschke R, Frenzel C, Glass X, Schulze J, Eickhoff A (2013) Herbal Hepatotoxicity: A Critical Review. Br J Clin Pharmacol 75:630

    Google Scholar 

  116. Geller SE, Shulman LP, van Breemen RB, Banuvar S, Epstein G, Hedayat S, Nikolic D, Krause EC, Piersen CE, Bolton JL, Pauli GF, Farnsworth NR (2009) Safety and Efficacy of Black Cohosh and Red Clover for the Management of Vasomotor Symptoms: A Randomized Controlled Trial. Menopause 16:1156

    Google Scholar 

  117. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J (2006) Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo: A Randomized Trial. Ann Int Med 145:869

    Google Scholar 

  118. Carpenter JS, Newton KM, Sternfeld B, Joffe H, Reed SD, Ensrud KE, Milata JL (2012) Laboratory and Ambulatory Evaluation of Vasomotor Symptom Monitors from the Menopause Strategies Finding Lasting Answers for Symptoms and Health Network. Menopause 19:664

    Google Scholar 

  119. Chan BY, Lau KS, Jiang B, Kennelly EJ, Kronenberg F, Kung AWC (2008) Ethanolic Extract of Actaea racemosa (Black Cohosh) Potentiates Bone Nodule Formation in MC3T3-E1 Preosteoblast Cells. Bone 43:567

    CAS  Google Scholar 

  120. Li JX, Liu J, He CC, Yu ZY, Du Y, Kadota S, Seto H (2007) Triterpenoids from Cimicifugae Rhizoma, a Novel Class of Inhibitors on Bone Resorption and Ovariectomy-Induced Bone Loss. Maturitas 58:59

    CAS  Google Scholar 

  121. Borrelli F, Izzo AA, Ernst E (2003) Pharmacological Effects of Cimicifuga racemosa. Life Sci 73:1215

    CAS  Google Scholar 

  122. Rhyu MR, Lu J, Webster DE, Fabricant DS, Farnsworth NR, Wang ZJ (2006) Black Cohosh (Actaea racemosa, Cimicifuga racemosa) Behaves as a Mixed Competitive Ligand and Partial Agonist at the Human Mu Opiate Receptor. J Agric Food Chem 54:9852

    CAS  Google Scholar 

  123. Reame NE, Lukacs JL, Padmanabhan V, Eyvazzadeh AD, Smith Yolanda R, Zubieta J-K (2008) Black Cohosh Has Central Opioid Activity in Postmenopausal Women: Evidence from Naloxone Blockade and Positron Emission Tomography Neuroimaging. Menopause 15:832

    Google Scholar 

  124. Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, Barton DL, Sloan JA, Lavasseur BI, Rao RM, Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, Richelson E, Fauq AH (2006) Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Black Cohosh in the Management of Hot Flashes: NCCYG Trial N01CC. J Clin Oncol 24:2836

    Google Scholar 

  125. Frei-Kleiner S, Schaffner W, Rahlfs VW, Bodmer C, Birkhauser M (2005) Cimicifuga racemosa Dried Ethanolic Extract in Menopausal Disorders: A Double-Blind Placebo-Controlled Clinical Trial. Maturitas 51:397

    CAS  Google Scholar 

  126. Drewe J, Zimmermann C, Zahner C (2013) The Effect of a Cimicifuga racemosa Extracts Ze 450 in the Treatment of Climacteric Complaints – an Observational Study. Phytomedicine 20:659

    CAS  Google Scholar 

  127. Raus K, Brucker C, Gorkow C, Wuttke W (2006) First-Time Proof of Endometrial Safety of the Special Black Cohosh Extract (Actaea or Cimicifuga racemosa Extract) CR BNO 1055. Menopause 13:678

    Google Scholar 

  128. Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD (2006) Black Cohosh and St. John’s Wort for Climacteric Complaints - a Randomized Trial. Obstet and Gynecol 107:247

    Google Scholar 

  129. Wuttke W, Gorkow C, Seidlova-Wuttke D (2006) Effects of Black Cohosh (Cimicifuga racemosa) on Bone Turnover, Vaginal Mucosa, and Various Blood Parameters in Postmenopausal Women: A Double-Blind, Placebo-Controlled, and Conjugated Estrogens-Controlled Study. Menopause 13:185

    Google Scholar 

  130. Schulz KF, Altman DG, Moher D, Consort Group (2010) Consort 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials. Ann Int Med 152:726

    Google Scholar 

  131. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C (2006) Reporting Randomized, Controlled Trials of Herbal Interventions: An Elaborated Consort Statement. Ann Int Med 144:364

    Google Scholar 

  132. Fabricant DS, Krause EC, Farnsworth NR (2010) Black Cohosh. In: Coates PM, Betz JM, Blackman MR (eds), Encyclopedia of Dietary Supplements. CRC Press, New York, p 60

    Google Scholar 

  133. Wuttke W, Jarry H, Haunschild J, Stecher G, Schuh M, Seidlova-Wuttke D (2014) The Non-Estrogenic Alternative for the Treatment of Climacteric Complaints: Black Cohosh (Cimicifuga or Actaea racemosa). J Ster Biochem Mol Biol 139:302

    Google Scholar 

  134. Shams T, Setia MS, Hemmings R, McCusker J, Sewitch M, Ciampi A (2010) Efficacy of Black Cohosh-Containing Preparations on Menopausal Symptoms: A Meta-Analysis. Alt Ther Health Med 16:36

    Google Scholar 

  135. Leach MJ, Moore V (2012) Black Cohosh (Cimicifuga spp.) for Menopausal Symptoms. Cochrane Database Systemat Rev 9:CD007244

    Google Scholar 

  136. Gertsch J (2011) Botanical Drugs, Synergy, and Network Pharmacology: Forth and Back to Intelligent Mixtures. Planta Med 77:1086

    CAS  Google Scholar 

  137. Sumner LW, Mendes P, Dixon RA (2003) Plant Metabolomics: Large-Scale Phytochemistry in the Functional Genomics Era. Phytochemistry 62:817

    CAS  Google Scholar 

  138. Watanabe K, Mimaki Y, Sakagami H, Sashida Y (2002) Cycloartane Glycosides from the Rhizomes of Cimicifuga racemosa and Their Cytotoxic Activities. Chem Pharm Bull 50:121

    CAS  Google Scholar 

  139. Linde H (1968) Die Inhaltsstoffe von Cimicifuga racemosa. 5. Mitt.: 27-Desoxyacetylacteol. Arch Pharm 301:335

    CAS  Google Scholar 

  140. Berger S, Junior P, Kopanski L (1988) 27-Deoxyactein: A New Polycyclic Triterpenoid Glycoside from Actaea racemosa. Planta Med 54:579

    CAS  Google Scholar 

  141. Linde H (1967) Die Inhaltsstoffe von Cimicifuga racemosa. 2. Mitt.: Zur Struktur des Acteins. Arch Pharm 300:885

    CAS  Google Scholar 

  142. Qiu F, Cai G, Jaki BU, Lankin DC, Franzblau SG, Pauli GF (2013) Quantitative Purity–Activity Relationships of Natural Products: The Case of Anti-Tuberculosis Active Triterpenes from Oplopanax horridus. J Nat Prod 76:413

    CAS  Google Scholar 

  143. Stöckigt J, Antonchick AP, Wu F, Waldmann H (2011) The Pictet-Spengler Reaction in Nature and in Organic Chemistry. Angew Chem Int Ed 50:8538

    Google Scholar 

  144. Kusano A, Takahira M, Shibano M, Miyase T, Okuyama T, Kusano G (1998) Studies on the constituents of Cimicifuga species. XXII. Structures of two new cyclolanostanol xylosides, cimiacerosides A and B. Heterocycles 48:1003

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA

    Feng Qiu & James B. McAlpine

  2. UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL, 60612, USA

    Elizabeth C. Krause, Shao-Nong Chen & Guido F. Pauli

Authors
  1. Feng Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James B. McAlpine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth C. Krause
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shao-Nong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guido F. Pauli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guido F. Pauli .

Editor information

Editors and Affiliations

  1. College of Pharmacy, The Ohio State University, Columbus, Ohio, USA

    A. D. Kinghorn

  2. Universität Linz Inst. Organische Chemie, Linz, Austria

    H. Falk

  3. Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

    J. Kobayashi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Qiu, F., McAlpine, J.B., Krause, E.C., Chen, SN., Pauli, G.F. (2014). Pharmacognosy of Black Cohosh: The Phytochemical and Biological Profile of a Major Botanical Dietary Supplement. In: Kinghorn, A., Falk, H., Kobayashi, J. (eds) Progress in the Chemistry of Organic Natural Products 99. Progress in the Chemistry of Organic Natural Products, vol 99. Springer, Cham. https://doi.org/10.1007/978-3-319-04900-7_1

Download citation

Publish with us

Policies and ethics

Search

Navigation