Black cohosh (Cimicifuga racemosa) for menopausal symptoms: A systematic review of its efficacy.

Since conventional hormone replacement therapy has fallen out of favour, alternatives are being sought by many women. These therapies include herbal preparations such as black cohosh (Cimicifuga racemosa). The purpose of this update of a previous systematic review is to evaluate the clinical evidence for or against the efficacy of black cohosh in alleviating menopausal symptoms. Five computerized databases (Medline, Embase, Amed, Phytobase and Cochrane Library) were searched to identify all clinical data that provided evidence on the efficacy of C. racemosa. Bibliographies of the articles thus located were scanned for further relevant publications. Only double blind, randomized, clinical trials (RCTs) were included in the evaluation of efficacy. No language restrictions were imposed. Trials were excluded if they did not focus on menopausal problems, they included women suffering medically induced menopause, they did not use black cohosh monopreparations, or they did not use placebo or a standard drug treatment for the control group. Six studies with a total of 1112 peri- and post-menopausal women met our inclusion criteria. The evidence from these RCTs does not consistently demonstrate an effect of black cohosh on menopausal symptoms; a beneficial effect of black cohosh on peri-menopausal women cannot be excluded. The efficacy of black cohosh as a treatment for menopausal symptoms is uncertain and further rigorous trials seem warranted.     

In vitro formation of quinoid metabolites of the dietary supplement Cimicifuga racemosa (black cohosh)

Botanical dietary supplements containing Cimicifuga racemosa (Actaea racemosa; black cohosh) are used commonly by women to assuage menopausal symptoms including hot flashes and sleep disorders. Despite the popularity of such supplements, little is known about the metabolism or possible toxicity of many compounds that could be concentrated therein. The aim of this study was to selectively identify phase I metabolites resulting from metabolic bioactivation of constituents of black cohosh in vitro and to determine whether evidence of such metabolites could be found in the urine of perimenopausal women taking black cohosh oral supplements. A variation of an ultrafiltration mass spectrometric assay devised previously was used to screen an extract of black cohosh for the formation of electrophilic phase I metabolites that had been trapped as GSH conjugates. Mercapturates (N-acetylcysteine conjugates) corresponding to the GSH conjugates identified during screening were synthesized and characterized using LC-MS/MS with product-ion scanning. During a phase I clinical trial of black cohosh in perimenopausal women, urine was collected from seven subjects, each of whom took a single oral dose of either 32, 64, or 128 mg of the black cohosh extract. These urine samples were analyzed for the presence of mercapturate conjugates using positive-ion electrospray LC-MS and LC-MS/MS. On the basis of their propensity to form GSH adducts following metabolic activation by hepatic microsomes and NADPH in vitro, a total of eight electrophilic metabolites of black cohosh were detected, including quinoid metabolites of fukinolic acid, fukiic acid, caffeic acid, and cimiracemate B. Additional quinoid metabolites were formed from hydroxytyrosol and dihydroxyphenyl lactic acid, neither of which had been isolated previously from black cohosh. However, mercapturate conjugates of these black cohosh constituents were not detected in urine samples from women who consumed single oral doses of up to 256 mg of a standardized black cohosh extract. Therefore, for moderate doses of a dietary supplement containing black cohosh, this study found no cause for safety concerns over the formation of quinoid metabolites in women.     

Cimicifuga racemosa: a systematic review of its clinical efficacy

BACKGROUND: Cimicifuga racemosa has long been advocated as an alternative to hormone-replacement therapy. However, recent experimental studies and a clinical trial have raised some questions on its utility. The aim of this systematic review is principally to summarise the trial evidence regarding the efficacy of C. racemosa in the treatment of menopausal symptoms. In addition, we also explore the evidence relating to the mechanism of action of this herbal medicine. METHODS: Searches of seven computerised databases were performed to identify all randomised clinical trials (RCTs) on C. racemosa as well as animal and in vitro experiments. No language restrictions were imposed. Data were extracted by both authors according to predefined criteria and are summarised in narrative form. RESULTS: Four RCTs of C. racemosa as a treatment of menopausal symptoms were included. They yielded no compelling evidence for the efficacy of C. racemosa on menopausal symptoms. The small beneficial effects observed in some studies could be explained by a central activity, and an oestrogenic activity cannot be completely excluded. CONCLUSIONS: In spite of plausible mechanisms of action of C. racemosa, its clinical efficacy for the treatment of menopausal symptoms has not been convincingly demonstrated through rigorous clinical trials. Additional rigorous RCTs and biochemical and chemical investigations are warranted.     

Triterpenoid glycoside from Cimicifuga racemosa

One new triterpene glycoside, cimiracemoside , and 14 known triterpene glycosides have been isolated from the rhizome extracts of black cohosh (Cimicifuga racemosa). On the basis of spectral and chemical evidence, the structure of the new compound was elucidated to be 12beta-acetoxycimigenol-3-O-beta-D-xylopranoside, and the known compounds were identified to be 25-acetylcimigenol xyloside, cimigenol-3-O-beta-D-xylopyranoside, acetin, 27-deoxyacetin, cimicifugoside H-1, 23-O-acetylshengmanol 3-O-beta-D-xylopranoside, foetidinol-3-O-beta-xyloside, cimicifugoside H-2, 25-O-methylcimigenol xyloside, 21-hydroxycimigenol-3-O-beta-D-xylopyranoside, 24-epi-7,8-didehydrocimigenol-3-xyloside, cimidahurinine, cimidahurine and cimifugin. The compounds, , and showed weak antibacterial activities in the agar diffusion assay.     

In vitro plant regeneration from leaf-derived callus of Cimicifuga racemosa

Cimicifuga racemosa (L.) Nutt., also known as Black Cohosh, is among the top 10 selling medicinal herbs in the United States. The rhizomes have been used to relieve menopausal discomfort. This plant is wild crafted and conservationists have expressed concerns with the sustainability of C. racemosa. Excised tissues from young leaves of C. racemosa were cultured on Murashige and Skoog's medium (MS) supplemented with various concentrations of NAA and TDZ for production of callus. The optimum callus growth and maintenance was in 1.0 microM NAA plus 0.5 microM TDZ. Two-month-old calli were sub-cultured on different concentrations of cytokinins (BA, kinetin, 2ip, TDZ) or in combination with GA(3) for shoot induction. The rate of shoot induction and proliferation was higher in MS media supplemented with 2.0 or 4.0 microM of TDZ. Concentrations of TDZ greater than 4.0 microM suppressed shoot growth. Adding 3.5 microM of GA(3) into media containing BA increased shoot growth. The presence of GA(3) with kinetin or TDZ did not affect shoot production. For rooting, shoots were transferred to MS medium with activated charcoal supplemented with various auxins (IAA, IBA and NAA), roots were noticed 20 days after transference. Activated charcoal was an essential component for vigorous rooting formation. Our results suggest that conservation of C. racemosa is possible through in vitro multiplication of leaf-derived callus.     

In vivo effects of black cohosh and genistein on estrogenic activity and lipid peroxidation in Japanese Medaka (Oryzias latipes)

This study was designed to assay the estrogenic activities and the antioxidant potential of ethanol extracts from the herbal dietary supplement black cohosh (Cimicifuga racemosa) relative to the natural phytoestrogen genistein. The in vivo mechanisms of action of these two natural products have not been completely elucidated, and Japanese medaka (Oryzias latipes) provides a useful organism for initial in vivo screening of natural products. While both genistein and estradiol altered ovarian and testicular steroid release and decreased circulating testosterone levels in males, neither black cohosh total extract (75-30,000 ng/fish), cimiracemoside A, 25-O-methyl-cimigenoside, actein, nor 26-deoxy-actein caused any differences in estrogenic activity compared to control fish. To assess antioxidant potential, animals were treated with natural products then challenged with 2-acetylaminofluorene (2-AAF) to induce lipid peroxidation (LPO) in the liver. Neither the total ethanol extracts from black cohosh nor its individual components showed an inhibitory effect in 2-AAF induced LPO. However, genistein manifested potent antioxidative activity in the LPO assay, with similar potency to a high dose of á-tocopherol. In contrast to genistein, black cohosh did not exhibit traditional estrogenic effects nor significant in vivo anti-oxidant potential in this fish model system.     

缓解围绝经期综合征的植物药——黑升麻异丙醇提取物（Remifemin）临床应用与评价

目的：评价缓解围绝经期综合征的植物药——黑升麻异丙醇提取物（Remifemin）临床应用概况。方法：收集国内外相关文献,从黑升麻异丙醇提取物（Remifemin）应用状况、有效性、安全性等方面进行分析评价。结果与结论：黑升麻异丙醇提取物（Remifemin）目前已普遍应用于临床,可以有效缓解围绝经期症状。     

Direct analysis and identification of triterpene glycosides by LC/MS in black cohosh, Cimicifuga racemosa, and in several commercially available black cohosh products

A method to directly identify triterpene glycosides using reversed-phase liquid chromatography with positive atmospheric pressure chemical ionization mass spectrometry (LC/(+)APCIMS) was developed. Based on the analysis of the molecular weight, fragment ions, selected ion chromatograms, a number of triterpene glycosides, including actein, 27-deoxyactein, cimicfugoside M, and cimicifugoside, from Cimicifuga racemosa were studied. A chromone, cimifugin, from C. foetida was also identified. Cimicifugoside M and cimifugin can specifically serve as indicators for species identification. The method can, therefore, be used to distinguish black cohosh products from among different plant species for quality control purposes.     

Cardiac activity of isolated constituents of Inula racemosa

Roots of the plant Inula racemosa are used as folk medicine in east Asia and Europe. Inula racemosa in combination with Commiphora mukul was reported to cure myocardial ischemia. However, systematic investigation of the plant for its specific role in heart diseases has not been conducted so far. In the present study, we have reported the isolation of four major constituents A, B, C and D along with some minor constituents from the plant Inula racemosa. Among the major constituent, constituent Dhas been selected first from spectral data and studied for its cardiac activity on isolated frog heart. The experimental data show that constituent D decreases heart rate and force of contraction at 40 mcg/ml. Actions of Adrenaline are blocked by constituent D and it also acts as an agonist for Propranolol. The studies indicate that constituent D produces a negative ionotropic and negative chronotropic effect on frog's heart. These studies can be utilized as a cardiac marker for exploring the cardiac activity of the plant Inula racemosa.     

Comparisons of Scutellaria baicalensis, Scutellaria lateriflora and Scutellaria racemosa: genome size, antioxidant potential and phytochemistry

The genus Scutellaria in the family Lamiaceae has over 350 species, many of which are medicinally active. One species, Scutellaria baicalensis, is one of the most widely prescribed plants in Traditional Chinese Medicine, used for neurological disorders, cancer and inflammatory diseases and has been the subject of detailed scientific study but little is known about the phytochemistry of other Scutellaria. The current study was designed to compare the medicinal phytochemistry of 3 species of Scutellaria used to treat neurological disorders. To accomplish this objective, the specific objectives were (a) to establish an in vitro collection of the South American native; S. racemosa, (b) to botanically characterize S. racemosa and (c) to compare the phytochemistry of S. racemosa with S. baicalensis and S. lateriflora. S. racemosa was established in vitro from wild populations in Florida. Botanically, S. racemosa is diploid with 18 chromosomes, and flow cytometry data indicated that S. baicalensis and S. racemosa have small nuclei with estimated small genomes (377 mbp and 411 mbp respectively). Antioxidant potential studies showed that there were no significant differences in the 3 Scutellaria species. Phytochemical analyses detected and quantified the flavonoids baicalin, baicalein, scutellarin, and wogonin as well as the human neurohormones melatonin and serotonin in leaf and stem tissues from S. baicalensis, S. lateriflora, and S. racemosa. These findings represent the first phytochemical analysis of S. racemosa and establish S. racemosa as a model system for study of medicinal plant secondary metabolism and as a potential source of important phytopharmaceuticals for treatment of human disease.     

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

Remifemin is an ethanolic extract of the rhizome of Cimicifuga racemosa (C.r.) and is used to relieve climacteric hot flushes. In the present study the effects of this preparation on LH and FSH secretion of menopausal women were investigated. After an 8 weeks treatment, LH but not FSH levels were significantly reduced in patients receiving the Cimicifuga extract. To further characterize the endocrinologically active principles of this plant extract, a lipophilic extract of C.r. was prepared and subjected to Sephadex chromatography. Fractions obtained were tested for their ability to reduce LH secretion in ovariectomized (ovx) rats and to compete in vitro with 17 beta-estradiol for estrogen receptor binding sites. Three types of endocrinologically active compounds were obtained: (1) Constituents which were not ligands for the estrogen receptor but suppress LH release after chronic treatment, (2) constituents binding to the estrogen receptor and also suppressing LH release, and (3) compounds which are ligands for the estrogen receptor but without an effect of LH release. It is concluded that the LH suppressive effect of C.r. extracts observed in menopausal women and ovx rats is caused by at least three different synergistically acting compounds.     

Herbal Therapies for Perimenopausal and Menopausal Complaints

Consumer use of alternative medicines in the United States is growing rapidly. Included in this phenomenon are herbal therapies instead of or as adjuncts with traditional medicine for perimenopausal and menopausal complaints. Of significant concern is the safety of these herbs. Since many women are using herbal therapies, clinicians must be knowledgeable about their use, quality, and safety. There are currently no government standards on the quality of herbal products in the United States, and some products are either unsafe or little is known scientifically about them. Selected herbal therapies touted in the lay press for common perimenopausal and menopausal complaints are examined, with advice on their use and safety based on scientific sources. (Pharmacotherapy 1997;17(5):970–984)     

Pregnane X receptor-mediated induction of Cyp3a by black cohosh

Black cohosh (BC) has been widely applied for the treatment of menopausal symptoms. However, increasing concerns about herb-drug interactions demand the need for studies on the influence of BC on cytochrome 450. Cyp3a11 in liver was induced by 7-fold in wild-type mice treated with 500?mg/kg black cohosh for 28 days compared with the control group as assessed by quantitative real-time PCR; no difference was found in small intestine and kidney, suggesting that up-regulation of Cyp3a11 by black cohosh was liver-specific. Western blot, activity assays, and pharmacokinetic analyses established dose- and time-dependent induction of Cyp3a11. To determine the mechanism of Cyp3a11 induction, including the role of pregnane X receptor (PXR) in vivo and in vitro, respectively, in Pxr-null, PXR-humanized, and double transgenic CYP3A4/hPXR mice, cell-based luciferase assays were employed revealing that mouse PXR played a direct role in the induction of Cyp3a11; human PXR was not activated by black cohosh. Overall, these findings demonstrate that induction of Cyp3a11 is liver-specific and involved only mouse PXR, not the human counterpart. Thus, the incidence of herb-drug interaction in patients administered black cohosh may not be mediated by human PXR and CYP3A4.     

Antitumor activity and antioxident role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice

AIM: To study the enzyme activity of CYP2C18 variant with exon 5 skipped. METHODS: A full length CYP2C18 cDNA X1 and an exon 5 skipped variant CYP2C18 X2 were separately subcloned into mammalian expression vector pREP9 to transfect HepG2 cells. The expression of CYP2C18 mRNA in transgenic cells and human liver tissues were determined by RT-PCR. The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC. The cytotoxicity of ifosfamide to transgenic cells was evaluated by MTT test. RESULTS: HepG2-CYP2C18 X1 cells showed strong expression of the full length CYP2C18 mRNA. On the other hand, HepG2-CYP2C18 X2 cells had only infinitesimal expression of the exon-skipped CYP2C18 as well as the full length CYP2C18, while non-transfected HepG2 cell only demonstrated an infinitesimal expression of the full length CYP2C18. The expression of CYP2C18 exons 2 to 7 was also analyzed by RT-PCR in 7 extratumoral liver tissues. Among them, 3 samples expressed on     

总状土木香中倍半萜内酯类同分异构体的鉴定与含量测定

目的 建立同时测定总状土木香药材中3个倍半萜类同分异构体的高效液相方法.方法 采用Agilent Zorbax XDB-C18 column（250 mm×4.6 mm,5 μm）;流动相：55%乙腈和45%水等度洗脱;流速1 mL/min;检测波长210 nm.结果 总状土木香药材中3个倍半萜类同分异构体Igalane、异土木香内酯和土木香内酯分别在17.40～1 740.00、21.20～2 120.00和20.40～2 040.00μg/ml的浓度范围内呈良好的线性关系,最低检测限分别为0.087、00.042和0.041μg/ml.重复性、稳定性的RSD均小于2.85%;各成分平均回收率均小于104.43%,RSD＆lt;1.20%.结论 该方法快速简便、准确可靠,各主要化学成分均能达到基线分离,适用于总状土木香药材的质量控制.另外,本实验采用液相半制备得到了两个倍半萜类同分异构体,并对它们的结构进行了鉴定.     

Antitumor activity and antioxidant role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice [corrected]

AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice.     

Sesquiterpenoids from Inula racemosa

Phytochemical research on the roots of Inula racemosa yielded nine sesquiterpenoids including a new nor-eudesmane-type sesquiterpenoid, 11,12,13-trinoreudesm-5-en-7β,8α-diol (1). The structures of isolated compounds were elucidated by extensive spectroscopic methods including 1D and 2D NMR. The structure of compound 2 was confirmed by single-crystal X-ray diffraction analysis.     

Evaluation of antiallergic activity (type I hypersensitivity) of Inula racemosa in rats.

Alcoholic extract of root of Inula racemosa, was studied for its antiallergic effect in experimental models of type I hypersensitivity, viz. egg albumin induced passive cutaneous anaphylaxis (PCA) and mast cell degranulation in albino rats. The alcoholic extract was prepared by the process of continuous heat extraction. LD50 of this extract was found to be 2100 +/- 60 mg/kg, i.p. Assessment of protection against egg albumin induced passive cutaneous anaphylaxix by different doses of Inula racemosa was done by giving drug intraperitoneally or orally for seven days or once only. Mast cell degranulation studies were done by using compound 48/80 as degranulation agent with same dosage schedule. Inula racemosa (i.p. as well as p.o.) showed significant protection against egg albumin induced PCA. Protection against compound 48/80 induced mast cell degranulation by alcoholic extract of Inula racemosa (single dose) was similar to that of disodium cromoglycate. The seven days drug treatment schedule showed greater protection than disodium cromoglycate intraperitoneally. The results suggest that Inula racemosa possesses potent antiallergic properties in rats.