Disease relevance of Cimicifuga

• PATIENTS AND METHODS: Patients diagnosed with breast cancer who had completed their primary treatment were randomly assigned to black cohosh or placebo, stratified on tamoxifen use [1].
• Therefore, the clinically observed estrogen-like actions of black cohosh, such as reduction of hot flashes, are likely due to a compound, or combination of compounds, other than formononetin [2].

High impact information on Cimicifuga

• An isopropanolic extract (iCR) from the rhizomes of Cimicifuga racemosa (black cohosh) is used an alternative in the treatment of menopausal symptoms, and animal studies suggest positive skeletal effects. iCR stimulated osteoblastic OPG protein secretion by 3- to 5-fold as early as 12 h without affecting RANKL expression [3].
• The iCR effect, abrogated by the pure estrogen receptor antagonist ICI 182,780, also enhanced ALP activity (4-fold) and osteocalcin expression (3-fold), possibly contributing to the skeletal effects of black cohosh [3].
• Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively [4].
• Chaste tree berry, black cohosh, and dong quai did not have measurable activity with this method [5].
• Further studies are needed to fully characterize whether these triterpene glycosides as well as other components of black cohosh in this plant extract bind to the estrogen receptor alpha (ER-alpha) [6].

Chemical compound and disease context of Cimicifuga

• CONCLUSIONS: The lack of proliferative effects of isopropanolic black cohosh extract on estrogen-sensitive breast cancer cells in vitro suggests a favorable safety profile for use in women with a history of breast cancer [7].
• Soy and other phytoestrogens, black cohosh, evening primrose oil, vitamin E, the bioflavonoid hesperidin with vitamin C, ferulic acid, acupuncture treatment, and regular aerobic exercise have been shown effective in treating hot flashes in menopausal women [8].

Biological context of Cimicifuga

• Estradiol induced stimulation of proliferation was inhibited by a dosage >1 microg/ml of extract concentration, gene expression was suppressed by doses of 100-1000 microg/ml of Cimicifuga racemosa extracts [9].
• Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans [10].
• The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers [11].
• Apoptosis of human prostate androgen-dependent and -independent carcinoma cells induced by an isopropanolic extract of black cohosh involves degradation of cytokeratin (CK) 18 [12].
• The present studies suggest the potential effect of fukinolic acid and cimicifugic acids of Cimicifuga rhizomes in preventing collagen degradation by collagenases or collagenolytic enzymes under pathological conditions, wound healing, or inflammation [13].

Anatomical context of Cimicifuga

• 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 [14].
• In the present experiments, the effects of the clinically used Cimicifuga racemosa (CR) extract BNO 1055 in the uterus, in the bone and on serum luteinizing hormone (LH) were compared with the effects of estradiol-17beta (E(2)) under acute and chronic conditions in ovariectomized rats [15].
• The effects of black cohosh extracts (Rhizoma Cimicifugae racemosae) on primary estrogen target organs, like mammary gland and endometrium are better described then those on other estrogen-sensitive systems e.g. the vasculature [16].
• We previously reported that the antiproliferative effect of an isopropanolic-aqueous extract of black cohosh (iCR) on MCF-7 estrogen-responsive breast cancer cell line was due to the induction of apoptosis [17].

Associations of Cimicifuga with chemical compounds

• The black cohosh preparation and one of the herbal combinations exhibited strong estrogen-antagonistic effects [7].
• Additional quinoid metabolites were formed from hydroxytyrosol and dihydroxyphenyl lactic acid, neither of which had been isolated previously from black cohosh [18].
• Caffeic acid, fukinolic acid as well as cimicifugic acids A, B, E and F isolated from the rhizomes of Cimicifuga racemosa (Ranunculaceae) inhibited the activity of neutrophil elastase (EC 3.4.21.37) in a dose-dependent manner [19].
• Black cohosh rhizomes were extracted with methanol/water and fractionated by solvent-solvent partitioning to yield three fractions: hexane, ethyl acetate and water [20].
• Based on these studies, structurally characteristic product ions and neutral molecule losses were identified, which were then used during LC/MS/MS with product ion scanning, precursor scanning and constant neutral loss scanning to detect caffeic acid derivatives in a crude extract of black cohosh [21].

Gene context of Cimicifuga

• Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant [4].
• We present a study on the mass spectral as well as the binding properties of three triterpene glycosides (cimicifugoside, cimiracemoside F, 27-deoxyactein) contained in black cohosh to the ligand binding domain of estrogen receptor beta (ER-beta) [6].
• OBJECTIVES: In this study, the effects of the Cimicifuga racemosa (CR) preparation CR BNO 1055 on markers of bone metabolism, hormones, sex hormone-binding globulin (SHBG), lipometabolism, vaginal maturity, and routine laboratory parameters were compared with those of conjugated estrogens (CE) and placebo [14].
• Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta [15].
• Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo [22].

Analytical, diagnostic and therapeutic context of Cimicifuga

• The black cohosh extracts increased the cytotoxicity of doxorubicin and docetaxel and decreased the cytotoxicity of cisplatin, but did not alter the effects of radiation or 4-hydroperoxycyclophosphamide (4-HC), an analog of cyclophosphamide which is active in cell culture [23].
• Its mechanism of action may involve estrogenic effects, but new data dispute the estrogenic theory and indicate that extracts of black cohosh do not bind to the estrogen receptor, up-regulate estrogen-dependent genes, or stimulate the growth of estrogen-dependent tumors in animal models [24].

References