Chapter 8
Modern Analytical Approaches in Quality Control of Black Cohosh 1
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2
R. Spreemann , H. Kurth 2 , M . Unger , and F. Gaedcke 1
2
Finzelberg, Inc., 2 Sylvan Way, Parsippany, NJ 07054 Finzelberg G m b H and Company KG, 56626 Andernach, Germany
Quality and reproduction of the constituents of an herbal drug preparation are of great importance to assure efficacy and safety of the resulting herbal medicinal product. Therefore, it is necessary to have optimized and validated analytical methods. For quality control the phytochemical characteri— zation of black cohosh rhizome and extracts focuses on the identification and quantitative determination of triterpene glycosides. Quantitative determination of the important triterpene glycosides actein, 27-desoxyactein, cimicifugoside and cimicifugoside M is done by RP-HPLC with Evaporative Light Scattering Detection (ELSD). Further marker substances like isoferulic acid are quantified if necessary by H P L C .
Black cohosh was introduced to Americans by Native Americans calling it "squaw root" or "snake root". Because it promotes and restores healthy menstrual activity it was predominantly used in treating uterine disorders and other female complaints (1). In 1989 the German Commission Ε published the Cimicifuga racemosa monograph indicating the use of black cohosh for treating premenstrual, dysmenorrhic and menopausal vegetative symptoms (2). The recommended daily dosage of Commission Ε is 40 mg herbal drug or equivalent herbal drug © 2002 American Chemical Society
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102 preparations being extracted with ethanol water 40-60%. Today the use of black cohosh focuses on the treatment of menopausal complaints and P M S (3). It is already very popular in Europe and we expect to see increased usage in the United States. Black cohosh could become of increasing interest to women looking for an alternative to estrogen therapy for the treatment of menopausal symptoms in the near future. Therefore it is very important to establish powerful analytical tools to describe the quality of the extract and hence to guarantee efficacy.
Constituents in Black Cohosh Black cohosh contains several important constituents (Figure 1). Among them, triterpene glycosides actein and deoxyactein, as well as cimicifugoside and cimicifugoside M are considered the main pharmacologically relevant constituents. Actein differs from deoxyactein in that it contains an additional hydroxyl group in position 27. The cimicifugosides contain a cyclopropane ring as a common structural feature, and are structurally related to cycloartenol. The structural difference between cimicifugoside M and cimicifugoside is due to the different sugar moieties (4). In a recent remarkable study a systematical investigation of triterpene glycosides was published (5). The authors reported about the isolation and structure of sixteen triterpene glycosides. Eight of them were described for the first time. Further Cimicifuga racemosa contains cinnamic acids, such as caffeic, ferulic and isoferulic acid. In the past there have been controversial reports by several authors about the isoflavone formononetin as a major active constituent assuming to have estrogen-like effects (6-8). According to our investigation formononetin occurs in the root in such small quantities, that it is hardly detectable in extracts with conventional H P L C methods. Further constituents are tannins, resins, fatty acids, starch and polysaccharides (9). Until today it was not possible to assign the active principle definitely to one or more of the constituents described above. However there are pharmacological hints that show that the triterpene glycosides might participate in the efficacy.
Monographs of Black Cohosh As shown in Table I there are only a few official monographs available for black cohosh rhizomes and extracts. The British Herbal Pharmacopoeia 1996 (BHP 1996), the German Homeopathic Pharmacopoeia (HAB 1) and the French Pharmacopoeia (for homeopathic preparations 1989) describe the herbal drug.
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Figure 1. Structures of several important constituents of black cohosh.
Usually only the description of the rhizomes (macroscopically and microscopically) is given as well as some additional parameters for purity (total ash, insoluble ash, loss on drying). The identity is checked by thin layer chromatography (TLC), but there are no requirements for minimum contents of triterpene glycosides or other constituents in these monographs The W H O draft monograph published in 1998, covers in addition to the common parameters mentioned testing on pesticides, heavy metals and radioactivity. A quantification of constituents was not required. This is because the aforementioned constituents were not thought to contribute to the efficacy of black cohosh until now. Therefore, the total extract, in its entirety is considered as the active substance. Dosage recommendations are given only by the Commission Ε monograph and the W H O draft monograph (1998). W H O has adopted the Commission Ε recommendations. The daily dosage for the extract is equivalent to 40 mg herbal drug following Commission Ε and WHO.
Finzelberg
WHO-draft 10/23/98
Commission Ε
ESCOP
(homéopatique)
PF 10
HPUS90
HAB1
BHP96
Monograph
Erg.B.6 Erg.B.6
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+
+
+
(+)
micro
macro
Description
Identification TLC
