Cimiracemates A–D, phenylpropanoid esters from the rhizomes of Cimicifuga racemosa

doi:10.1016/S0031-9422(02)00209-1

Phytochemistry

Volume 61, Issue 4, October 2002, Pages 409-413

https://doi.org/10.1016/S0031-9422(02)00209-1 Get rights and content

Abstract

Four phenylpropanoid esters, cimiracemates A–D (1–4), along with three known compounds, isoferulic acid, ferulic acid and methyl caffeate were isolated from the EtOAc fraction of the rhizome of Cimicifuga racemosa. The structures of the esters were elucidated by means of spectral data, including 2D NMR spectroscopy.

Four phenylpropanoid esters, cimiracemates A–D (1–4), were isolated from the EtOAc fraction of the rhizome of C. racemosa. Their structures were elucidated by means of spectral methods, including 2D NMR spectroscopy.

Introduction

The roots and rhizomes of Cimicifuga racemosa (L.) Nutt. (Actaea racemosa L.) (Ranunculaceae) (Compton et al., 1998), commonly known as black cohosh, have a long and diverse history of medicinal use dating back to native North American indigenous groups (Foster, 1999, McKenna et al., 2001). It is presently used in the treatment of climacteric symptoms related to menopause (Liske, 1998, Lieberman, 1998), with a clinical history spanning over the last 40 years (Stielhler, 1959, Foeldes, 1959, Stefan, 1959, Brucker, 1960, Schildge, 1964, Stolze, 1982, Vorberg, 1984, Jarry and Harnischfeger, 1985, Jarry et al., 1985, Pethoe, 1987, Duker et al., 1991). As part of our studies on botanical dietary supplements for women's health, we have been investigating the biological and chemical profiles of the rhizomes of this plant. Previously, we reported on the isolation and structure elucidation of 26-deoxyactein and the clarification of the nomenclature of 27-deoxyactein (Chen et al., 2002b), as well as on the isolation and structure determination of eight new 9,19-cyclolanostane-triterpene glycosides (cimiracemosides I-P) (Chen et al., 2002a).

In the present investigation, four phenylpropanoid esters, cimiracemates A–D (1–4) were isolated along with three known compounds: isoferulic acid, ferulic acid, and methyl caffeate from the rhizomes of C. racemosa. In this paper, the isolation of these compounds and the elucidation of their structures by means of spectral data are described.

Section snippets

Results and discussions

Cimiracemates A–D (1–4) were obtained by repeated chromatography of the EtOAc fraction prepared from the rhizomes of C. racemosa by sequential chromatography on silica gel (SiO₂) and RP-18 columns, and C-18 HPLC.

Cimiracemate A (1) was obtained as a light brown powder. The molecular formula was determined to be C₁₉H₁₈O₇ on the basis of a negative HR-ESIMS m/z 357.0974 (calc. 357.0974 for C₁₉H₁₇O₇). UV absorptions at 291 (log ε: 3.77) and 325 (log ε: 3.96) nm showed that 1 has a conjugated

General

Mps uncorr. TLC precoated Kieselgel 60 F₂₅₄ Si and RP-18 (0.25 mm, Merck). CC silica gel (mesh 230–400) eluted with CHCl₃–MeOH (gradient) or CHCl₃–acetone–H₂O (17:1:0.1), and CC RP-18 (Lobar Lichroprep, 40–63 μm, 25×310 mm, Merck) eluted with MeOH–H₂O (55:45) at the rate of 4 ml/min, 5% H₂SO₄ in n-BuOH and UV were used for detection of TLC. Semi-preparative HPLC was carried out on a Waters 996 system equipped with a photodiode array detector on a Watrex GROM-Sil 120 ODS-4 HE semipreparative

Acknowledgements

This research was funded by grant No. P50 AT00155 through the National Center for Complementary and Alternative Medicine (NCCAM), the Office of Dietary Supplements (ODS), the National Institute of General Medicine (NIGMS), and the Office for Research on Women's Health (ORWH). Contents are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM, ODS, NIGMS or ORWH.

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Isolation, structure elucidation, and absolute configuration of 26-deoxyactein from Cimicifuga racemosa and clarification of nomenclature associated with 27-deoxyactein
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A review of the genus Actaea L.: ethnomedical uses, phytochemical and pharmacological properties
2023, Journal of Herbal Medicine
The genus Actaea L., comprising 32 species, has recently emerged as a source of potential phytochemicals with promising pharmacological properties. However, there is no review available integrating the scattered scientific studies on this genus. To fill this knowledge gap, an extensive review of the genus Actaea is presented with a focus on its ethnomedical uses, phytochemistry, and pharmacology.
For this review, 162 publications including 152 research papers, seven books, two dictionaries, and one glossary published from 1896 to April 2020 A.D. were critically reviewed and relevant data extracted. The chemical structures and formulae of compounds have been sourced and validated using PubChem database, and drawn using Chem Draw Ultra 6.0. The scientific nomenclature follows The Plant List.
For over more than a century, the ethnomedical uses of eight species of this genus in treating 29 types of human diseases under different traditional medical systems have been reported. Over the last two decades, the phytochemical studies so far conducted on 16 species of Actaea have led to the isolation of more than 400 different compounds, notably cycloartane triterpenoids, flavonoids, phenylpropanoids, and nitrogenous compounds. Based on these phytochemical studies on Actaea species, the recent resurgence on pharmacological research conducted on 16 species has led to novel leads with potential applications.
We highlight the current knowledge gaps and discuss future research prospects on the genus Actaea, which can guide its bio-prospection and sustainable use in the near future.
Traditional uses, phytochemistry, pharmacology and toxicology of the genus Cimicifuga: A review
2017, Journal of Ethnopharmacology
Citation Excerpt :
Cimicifuga is the rare plants containing both ferulic acid and isoferulic acid. Furthermore, phenolic acids, namely fukiic acid derivatives, including cimicifugic acids A-J (400-402,404-410), shomasides A-E (396-399,403) (Miyase et al., 2010), and cimiracemates A-D (413-416) (Fong et al., 2002b), are characteristic chemical constituents of the genus Cimicifuga. There are certain differences between the phenolic acids within different species of Cimicifuga spp. (Szymczak et al., 2015).
Plants of the genus Cimicifuga have long been used as an ethnomedicine in China, Europe, and North America for its high medicinal value and health benefits. Their dried rhizomes are widely used for treating wind-heat headache, toothache, aphtha, sore throat, measles, spot poison, archoptosis, and uterine prolapse. In addition, it is used as a dietary supplement for preventing women menopausal symptoms and osteoporosis.
This paper aims to provide up-to-date information on the genus Cimicifuga, including botanical characterization, medicinal resources, traditional medicinal uses, phytochemistry, quality control, pharmacological research as well as the toxicology. The possible structural-activity relationships and molecular mechanisms of the bioactive constituents are discussed in ways that contribute to the structural optimization and preclinical safety assessment for further drug design.
The relevant information on Cimicifuga was collected from scientific databases (such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, CNKI, Baidu Scholar, Web of Science, China Knowledge Resource Integrated Database), Chinese herbal classics, ethnobotanical books, PhD and MSc dissertations, Chinese Pharmacopoeia, published articles in peer-reviewed journals, local magazines, and unpublished materials. In addition, the Plant List (TPL, www.theplantlist.org) was also used to validate the scientific names and synonyms of this plant. The literature cited in this review dated from 1953 to 2017.
The majority of chemical constituents of this plant include triterpenoid glycosides, phenylpropanoids, nitrogenous compounds, chromones, flavonoids and 4α-methyl steroid. Among them, the primary bioactive constituents are believed to be present in the triterpene glycoside fraction. To date, investigation of seven Cimicifuga spp. plants led to the identification of more than 457 compounds. Years of pharmacological research proved that the crude extracts and certain pure compounds obtained from Cimicifuga exhibited menopausal syndrome-treatment, anti-osteoporosis, antiviral, antitumor, antioxidant and antiangiogenic activities. On the other hand, Cimicifuga plant-induced toxicities of liver, cardiovascular, central and peripheral nervous systems have also been reported. Therefore, safety consideration should be placed into a high priority for herbal medicine Cimicifuga therapy in the early stages of development and clinical trials.
This review presents information on botany, medicinal resources, and traditional medicinal history of some Cimicifuga plants. Modern pharmacology researchers have validated many traditional uses of Cimicifuga species. As the quality control and safety assessment of Cimicifuga plants is still incomplete, only a small part of the plant is permitted to be used as medicines. Expansion of medicinal resources in Cimicifuga is urgently needed to enable its full use. Currently research primarily focuses on the triterpenoid glycosides but there are many other types of compounds which may possess new biological activities however the systematic studies of these compounds are lacking. Extensive study is required on Cimicifuga plant before it can be fully used in clinics as a potent drug candidate.
Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells
2009, Chemico-Biological Interactions
Citation Excerpt :
The coumarin was identified as 6,7-dimethoxycoumarin (5) [16]. The flavonoids were found to be quercetin (7) [17], luteolin (6) [18], afzelechin (1) [19] and catechin (3) [20] while the isolated phenolic acids were identified as 3-hydroxy, 4-methoxy-benzoic acid (4) [21], galloyl quinic acid (2) [22] and ferulic acid (8) [23]. The antioxidant activity of C. rotundus extracts was carried out to follow both the superoxide scavenging ability and also inhibition of xanthine oxidase activity.
A Total Oligomers Flavonoids (TOFs) and ethyl acetate extracts of Cyperus rotundus were analyzed, in vitro, for their antioxidant activity using several biochemical assays: the xanthine (X)/xanthine oxidase (XO), the lipid peroxidation induced by H₂O₂ in K562 human chronic myelogenous leukemia cells and the DNA damage in pKS plasmid DNA assay induced by H₂O₂/UV-photolysis and for their apoptotic effect. TOF and ethyl acetate extracts were found to be efficient in inhibiting xanthine oxidase with IC₅₀ values of 240 and 185 μg/ml and superoxide anion with IC₅₀ values of 150 and 215 μg/ml, respectively. Also, all the extracts tested were effective in reducing the production of thiobarbituric acid reactive substances (TBARS) and were able to protect against H₂O₂/UV-photolysis induced DNA damage. The highest activity, measured as equivalents of MDA concentration, was observed in the ethyl acetate extract (MDA = 2.04 nM). In addition, the data suggest that only TOF enriched extract exerts growth inhibition on K562 cells through apoptosis induction. Therefore, these extracts were subjected to further separation by chromatographic methods. Thus, three major compounds (catechin, afzelechin and galloyl quinic acid) were isolated from the TOF enriched extract and five major compounds (luteolin, ferulic acid, quercetin, 3-hydroxy, 4-methoxy-benzoic acid and 6,7-dimethoxycoumarin) from ethyl acetate extract. Their structures were determined by spectroscopic data analysis and comparison with the literature. In addition, we evaluate the biological activities of the catechin, ferulic acid and luteolin. This investigation has revealed that the luteolin was the most active in reducing the production of TBARS (MDA = 1.5 nM), inhibiting significantly the proliferation of K562 cells (IC₅₀ = 25 μg/ml) and protecting against H₂O₂/UV-photolysis induced DNA damage. In conclusion, the study reveals that the ability of C. rotundus to inhibit the enzyme xanthine oxidase (XO), the lipid peroxidation and to exert apoptotic effect, may explain possible mechanisms by which C. rotundus exhibits its health benefits.
A Triterpene Glycoside from Black Cohosh that Inhibits Osteoclastogenesis by Modulating RANKL and TNFα Signaling Pathways
2007, Chemistry and Biology
Citation Excerpt :
Therefore, black cohosh may confer its bone loss-protection effects through a novel mechanism rather than the estrogenic pathway. The accumulated phytochemical studies reveal that black cohosh contains structurally diversified cycloartane triterpene glycosides and aromatic acids as the major constituents [11, 22–24]. Although cycloartane triterpene glycosides have cytotoxicity or antiproliferation activity against cancer cells [25–29] and aromatic acids have antioxidant activity [30], none of them has been investigated for their effects on bone cells.
Osteoporosis is a major age-related source of morbidity and mortality. Increased bone resorption mediated by osteoclasts is central to its pathogenesis. Cytokines, particularly RANKL and TNFα, are often increased under pathologic conditions, leading to enhanced osteoclastogenesis. Black cohosh (Actaea/Cimicifuga racemosa L), a popular herbal supplement for the treatment of menopausal symptoms, was recently shown to have the beneficial effect of preventing bone loss. Here, we demonstrate that 25-acetylcimigenol xylopyranoside (ACCX), a triterpenoid glycoside isolated from black cohosh, potently blocks in vitro osteoclastogenesis induced by either RANKL or TNFα. This blockage of osteoclastogenesis elicited by ACCX results from abrogation of the NF-κB and ERK pathways induced by either RANKL or TNFα, respectively. Importantly, this compound attenuates TNFα-induced bone loss in vivo. Therefore, ACCX represents a potential lead for the development of a new class of antiosteoporosis agents.
9,10-seco-9,19-Cyclolanostane arabinosides from the roots of Actaea podocarpa
2007, Phytochemistry
Seven 9,10-seco-9,19-cyclolanostane arabinosides, named podocarpasides A–G (1–7), were isolated from the roots of Actaea podocarpa DC., a species closely related to black cohosh (a well known dietary supplement). Their structures were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The isolates were found inactive, when tested for cytotoxic, estrogenic, and antioxidant activities in cell based assays. They were also tested for anticomplement activity against the classical pathway of complement system and only podocarpaside C (3) inhibited modest complement activity with an IC₅₀ value of 200 μM.
Benefits of Black Cohosh (Cimicifuga racemosa) for Women Health: An Up-Close and In-Depth Review
2022, Pharmaceuticals

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Phytochemistry

Abstract

Introduction

Section snippets

Results and discussions

General

Acknowledgements

References (20)

Liquid chromatographic-electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide

J. Chromatography A

Polyazetylenverbindungen, 243—Über die Inhaltsstoffe von Coreopsis parvifolia Blake

Chem. Ber.

Beitrag zur Phytotherapie hormonaler Störungen der Frau

Die Medizinische Welt

Cimiracemosides I-P, new 9,19-cyclolanostane-triterpene glycosides from Cimicifuga racemosa

J. Nat. Prod.

Isolation, structure elucidation, and absolute configuration of 26-deoxyactein from Cimicifuga racemosa and clarification of nomenclature associated with 27-deoxyactein

J. Nat. Prod.

Reclassification of Actaea to include Cimicifuga and Souliea (Ranunculaceae): phylogeny inferred from morphology, nrDNA ITS, and cpDNA trnL-F sequence variation

Taxon

Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats

Planta Med.

Die Wirkungen eines Extraktes aus Cimicifuga racemosa

Aerztliche Forschung

Black cohosh: Cimicifuga racemosa a literature review

Herbalgram

Untersuchungen zur endokrinen Wirksamkeit von Inhaltsstoffen aus Cimicifuga racemosa. 1. Einfluss auf die Serumspiegel von Hypophysenhormonen ovariektomierter Ratten

Planta Med.

Cited by (39)

A review of the genus Actaea L.: ethnomedical uses, phytochemical and pharmacological properties

Traditional uses, phytochemistry, pharmacology and toxicology of the genus Cimicifuga: A review

Relationship correlation of antioxidant and antiproliferative capacity of Cyperus rotundus products towards K562 erythroleukemia cells

A Triterpene Glycoside from Black Cohosh that Inhibits Osteoclastogenesis by Modulating RANKL and TNFα Signaling Pathways

9,10-seco-9,19-Cyclolanostane arabinosides from the roots of Actaea podocarpa

Benefits of Black Cohosh (Cimicifuga racemosa) for Women Health: An Up-Close and In-Depth Review