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Wolfgang Wuttke - One of the best experts on this subject based on the ideXlab platform.

  • Absence of positive effect of black cohosh (Cimicifuga Racemosa) on fracture healing in osteopenic rodent model
    Phytotherapy Research, 2010
    Co-Authors: L. Kolios, Wolfgang Wuttke, F. Daub, Stephan Sehmisch, Karl Heinz Frosch, M. Tezval, K. M. Stuermer, E. K. Stuermer
    Abstract:

    The healing of predominantly metaphyseal fractures in postmenopausal osteoporosis is delayed and comparatively poor. Due to the potential side effects of HRT, natural alternatives are appealing. The aim of this study was to determine whether Cimicifuga Racemosa Extract BNO 1055 improves metaphyseal fracture healing in severe osteopenic bone in rats. Thirty-three 12-week-old female rats developed severe osteopenia during 10 weeks after ovariectomy. After metaphyseal tibial-osteotomy and standardized T-plate-osteosynthesis, the healing periods in ovariectomized rats (C), 17-α-estradiol (E) and Cimicifuga Racemosa (CR) supplemented diets were assessed for 35 days. Changes in callus morphology were evaluated qualitatively by biomechanical testing and quantitatively in microradiographies and fluorochrome-labeled histological sections. The CR-supplementation slightly improved callus quality and trabecular bone formation. It significantly enhanced the endosteal callus density compared to C group (Cl.Dn.e C: 59.08 ± 21.89, E: 45.95 ± 18.39, CR: 60.85 ± 18.66*), though most of the other morphological parameters examined showed no improvement. The time course of fracture healing did not change due to CR. Estrogen-supplementation enhanced the biomechanical properties of the fracture site. Trabecular bone was improved indicating the physiological endosteal healing process. The CR-supplementation did not exhibit positive effects in severe (senile) osteopenic fracture healing as seen in early (postmenopausal) osteoporosis in rats. Callus formation was slightly improved under CR. Estrogen improved fracture healing in severe osteopenic bone, while the extent of callus formation played a minor role. Copyright © 2010 John Wiley & Sons, Ltd.

  • Reprint of Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy?
    Maturitas, 2008
    Co-Authors: Wolfgang Wuttke, Christoph Gorkow, Hubertus Jarry, Volker Christoffel, Tamara Becker, Alexander Schultens, Dana Seidlova-wuttke
    Abstract:

    Abstract Objectives: This review presents findings with clear statements from the literature as well as own results of effects of soy, red clover and their isoflavones as well as of the Cimicifuga Racemosa Extract BNO 1055. Experimental and clinical effects on climacteric complaints, osteoprotective effects, activity in the urogenital tract, and risks concerning cardiovascular diseases and mammary and endometrial tissue will be compared, also in comparison to classical hormone preparations. The question whether soy and red clover products and/or Cimicifuga Racemosa (CR) preparations are endocrine disrupters or may fulfill the criteria of the so-called phyto-SERMs will be discussed. Methods: Review of selected publications since 1980 and summary of unpublished own results of the authors. Results: Experimental and clinical evidences suggest that soy/red clover and their isoflavones do not fulfill the criteria of an ideal SERM. They appear to have mild osteoprotective effects but do not improve climacteric complaints. Furthermore, they seem to stimulate uterine growth and mammary epithelial proliferation. In ovariectomized rats, the CR Extract BNO 1055 showed many of the beneficial effects of 17b-estradiol, including effects in the brain/hypothalamus to reduce serum LH levels, effects in the bone to prevent osteoporosis and estrogenic effects in the urinary bladder. The CR Extract BNO 1055 had no uterotrophic effect. Conclusion: If clinical studies confirm these results, the Cimicifuga Racemosa preparation BNO 1055 would appear as an ideal SERM and may therefore be an alternative to hormone replacement therapy.

  • first time proof of endometrial safety of the special black cohosh Extract actaea or Cimicifuga Racemosa Extract cr bno 1055
    Menopause, 2006
    Co-Authors: Karel Raus, Cosima Brucker, Christoph Gorkow, Wolfgang Wuttke
    Abstract:

    Objective: To investigate endometrial safety by assessment of endometrial biopsy samples and the tolerability and efficacy of the special Actaea or Cimicifuga Racemosa Extract (CR BNO 1055). Design: Four hundred postmenopausal women with symptoms related to estrogen deficiency were enrolled into a prospective, open-label, multinational, multicenter study. Treatment duration (daily dose corresponds to 40 mg of herbal drug) was 52 weeks. To determine the probability of endometrial hyperplasia and more serious adverse endometrial outcome, the point estimator and upper limit of 95% CI were calculated. Descriptive statistics were used to assess the secondary endpoints. Results: Endometrial safety has been proven because no case of hyperplasia or more serious adverse endometrial outcome occurred (point estimate: 0.0; upper limit of 95% CI: 0.011). Endometrial thickness, which was measured by endovaginal ultrasonography, did not show an increase. The number and intensity of hot flushes were markedly decreased. The dropout rate was less than 10%. The overall tolerability was good. Conclusions: The lack of endometrial proliferation and improvement of climacteric complaints as well as only a few gynecologic organ-related adverse events are reported for the first time after a treatment period of 1 year. Due to the improved benefit:risk ratio, it must be assumed that the Cimicifuga Racemosa special Extract BNO 1055 is a safe alternative for treatment of climacteric complaints.

  • inhibitory effects of a black cohosh Cimicifuga Racemosa Extract on prostate cancer
    Planta Medica, 2006
    Co-Authors: Dana Seidlovawuttke, Paul Thelen, Wolfgang Wuttke
    Abstract:

    The Cimicifuga Racemosa Extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore, we tested the capability of this Extract to inhibit formation and/or proliferation of tumors induced by subcutaneous (s. c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of 1 million cells, 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals and the size of the latter at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection, the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. The CR treatment did not affect serum testosterone levels significantly regardless of whether the animals developed tumors or not. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s.c. inoculation of LNCaP cells. Hence, the CR Extract may prove to be efficient in preventing and treatment of prostate cancer.

  • evidence for selective estrogen receptor modulator activity in a black cohosh Cimicifuga Racemosa Extract comparison with estradiol 17beta
    European Journal of Endocrinology, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Barbara Spengler, Volker Christoffel, Tamara Becker, Oda Hesse, Wolfgang Wuttke
    Abstract:

    Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. 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-17b (E2) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E2 or the CR Extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E2 and the CR Extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E2 and partially by CR supplementation. Conclusions: These data confirm the concept that the CR Extract BNO 1055 contains as yet unidentified substances with SERM properties which act in the hypothalamo/pituitary unit and in the bone but not in the uterus.

Hubertus Jarry - One of the best experts on this subject based on the ideXlab platform.

  • Reprint of Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy?
    Maturitas, 2008
    Co-Authors: Wolfgang Wuttke, Christoph Gorkow, Hubertus Jarry, Volker Christoffel, Tamara Becker, Alexander Schultens, Dana Seidlova-wuttke
    Abstract:

    Abstract Objectives: This review presents findings with clear statements from the literature as well as own results of effects of soy, red clover and their isoflavones as well as of the Cimicifuga Racemosa Extract BNO 1055. Experimental and clinical effects on climacteric complaints, osteoprotective effects, activity in the urogenital tract, and risks concerning cardiovascular diseases and mammary and endometrial tissue will be compared, also in comparison to classical hormone preparations. The question whether soy and red clover products and/or Cimicifuga Racemosa (CR) preparations are endocrine disrupters or may fulfill the criteria of the so-called phyto-SERMs will be discussed. Methods: Review of selected publications since 1980 and summary of unpublished own results of the authors. Results: Experimental and clinical evidences suggest that soy/red clover and their isoflavones do not fulfill the criteria of an ideal SERM. They appear to have mild osteoprotective effects but do not improve climacteric complaints. Furthermore, they seem to stimulate uterine growth and mammary epithelial proliferation. In ovariectomized rats, the CR Extract BNO 1055 showed many of the beneficial effects of 17b-estradiol, including effects in the brain/hypothalamus to reduce serum LH levels, effects in the bone to prevent osteoporosis and estrogenic effects in the urinary bladder. The CR Extract BNO 1055 had no uterotrophic effect. Conclusion: If clinical studies confirm these results, the Cimicifuga Racemosa preparation BNO 1055 would appear as an ideal SERM and may therefore be an alternative to hormone replacement therapy.

  • Cimicifuga Racemosa Extract for the treatment of climacteric complaints
    Journal of Endocrinology and Reproduction, 2006
    Co-Authors: W Wuttke, Hubertus Jarry, Dana Seidlovawuttke
    Abstract:

    Cimicifuga Racemosa (CR) is widely used to treat climacteric complaints. These complaints, particularly hot flushes, are associated with over-activity of GnRH pulse generator in the hypothalamus, which is significantly reduced by E 2 . These effects can be ideally studied in ovariectomized (ovx) rats. In the present contribution we show that over-activity of GnRH pulse generator in the rat model is reduced by E 2 and by CR BNO 1055 as reflected in the reduced LH pulse amplitudes. This effect is not mediated by the pituitary because the Extract had no effect on LH and TSH secretion but significantly inhibited prolactin release from cultured pituitary cells indicating the presence of dopaminergic compounds. Both, E 2 and CR treatment of ovx rats had profound effects on the expression of ER-alpha and ER-beta genes in the medio-basal hypothalamus and the preoptic area and both the compounds stimulated tyrosine hydroxylase gene expression in the preoptic area. This hypothalamic site is the location of GnRH perikarya. It can, therefore, be concluded that catecholaminergic mechanisms are involved in the modality by which the E 2 and CR inhibit the over-activity of the GnRH pulse generator in ovx rats and in postmenopausal women.

  • Cimicifuga Racemosa Extract bno 1055 inhibits proliferation of the human prostate cancer cell line lncap
    Phytomedicine, 2005
    Co-Authors: Hubertus Jarry, Paul Thelen, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Extracts from black cohosh (Cimicifuga Racemosa, CR) exert an anti-proliferative action in human breast cancer cell cultures, which has been attributed to an anti-estrogenic effect. However, CR constituents do not bind to either of the known estrogen receptors. Thus, the anti-tumor effect of CR me be mediated by mechanisms not involving these receptors. Polycyclic aromatic hydrocarbons are toxic environmental pollutants, which indirectly act as anti-estrogens by activating the aryl hydrocarbon receptor (AhR). The AhR is widely expressed in mammalian tissues and tumors. A recent screening study demonstrated activation of the AhR by a variety of herbal Extracts, among others, CR. Since activation of the AhR causes inhibition of growth of prostate cancer cells, we addressed the question, whether CR may not only inhibit growth of breast cancer — but also of prostate cancer cells. In the AhR ligand assay, the CR Extract BNO 1055 reduced tracer binding to 71% of the control demonstrating interaction of constituents of this Extract with the receptor. Under basal as well as under estradiol- and dihydrotestosterone stimulated conditions, the CR Extract dose dependently inhibited proliferation of LNCaP cells. A significant reduction of cell growth was observed at a concentration as low as 50 ng/ml. Thus, it is demonstrated for the first time that CR compounds potently inhibit the growth of human prostate cancer cells in vitro. This anti-proliferative effect may be mediated via the AhR.

  • evidence for selective estrogen receptor modulator activity in a black cohosh Cimicifuga Racemosa Extract comparison with estradiol 17beta
    European Journal of Endocrinology, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Barbara Spengler, Volker Christoffel, Tamara Becker, Oda Hesse, Wolfgang Wuttke
    Abstract:

    Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. 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-17b (E2) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E2 or the CR Extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E2 and the CR Extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E2 and partially by CR supplementation. Conclusions: These data confirm the concept that the CR Extract BNO 1055 contains as yet unidentified substances with SERM properties which act in the hypothalamo/pituitary unit and in the bone but not in the uterus.

  • in vitro effects of the Cimicifuga Racemosa Extract bno 1055
    Maturitas, 2003
    Co-Authors: Hubertus Jarry, Maria Metten, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Objectives: Extracts of Black cohosh ( Cimicifuga Racemosa or CR) have been used for the treatment of climacteric complaints since decades. Efficacy, particularly concerning neurovegetative and psychic symptoms, has been proven in clinical trials. As active principle yet unknown substances with selective estrogen receptor modulator (SERM) activity are assumed. Recently, evidence arose that CR may also contain dopaminergic compounds, which may contribute to the therapeutic activity of the Extract. Methods: Two subtypes of the estrogen receptor (ERα and ERβ) are known. To examine, whether active substances of CR Extract BNO 1055 (which is contained in Klimadynon® and Menofem®) bind to either of the two estrogen receptors, subtype-specific estrogen receptor ligand-binding assays with recombinant ERα or ERβ were conducted. A ligand-binding assay with recombinant dopamine D 2 -receptor protein was employed to assess possible dopaminergic activity in the CR Extract BNO 1055. Results: While a displacement of radiolabeled estradiol from binding sites of a cytosol preparation from procine and human endometrium by CR Extract BNO 1055 was shown no such displacement was achieved when either ERα or ERβ protein was used as ligands for tracer. Dopaminergic activity in the CR Extract BNO 1055 could be demonstrated with the D 2 -receptor assay. A countercurrent chromatography resulted in a separation of estrogenic and dopaminergic activity in two distinct fractions. Conclusions: It is suggested that not yet identified substances in the CR Extract BNO 1055 bind to a yet unknown estrogen-binding site in the endometrium. Also, yet unknown dopaminergic compounds may contribute to the pharmacological profile of CR Extract BNO 1055.

W Wuttke - One of the best experts on this subject based on the ideXlab platform.

  • antiosteoporotic effects of the special Cimicifuga Racemosa Extract bno 1055
    European Journal of Integrative Medicine, 2008
    Co-Authors: D Seidlovawuttke, W Wuttke
    Abstract:

    We and others have recently shown that Extracts of the rhizome of black cohosh (Cimicifuga Racemosa=CR) contains one or several substance(s) that prevent osteoporosis in gonadectomized female and male rats. In two double-blind placebo-controlled trials in postmenopausal women, surrogate parameters of bone metabolism were also improved, indicating the reduction of osteoclasts and a stimulation of osteoblast activity. The mechanisms of actions, however, still remained unknown. It is known that osteoblasts produce the ligand for the receptor activator of NF-kB (Rank), which stimulates osteoclastogenesis and function. Osteoprotegerin (OPG) is another osteoblast product and is a decoy receptor for RANKL. Its high production prevents RANKL to activate RANK and thereby OPG inhibits osteoclastogenesis and function. Furthermore, osteoblasts produce Osteocalcin, a protein that is essential for proper bone formation. To elucidate the function of the special CR Extract BNO 1055 serum concentrations of RANKL, OPG and Osteocalcin were measured in female and male rats treated with 33 mg of the CR Extract BNO 1055 orally over a period of 3 months. For positive control purposes, female ovariectomized rats were substituted with estradiol (E2) and males with E2 and testosterone (T). E2 and CR BNO 1055 suppressed serum RANKL concentrations in the serum significantly while E2 inhibited CR BNO 1055-stimulated Osteocalcin production, reflecting an increased serum concentration. The production of OPG was also inhibited by E2 but unaffected by CR BNO 1055. Quantitative computer tomography and histomorphometry indicated significantly less deterioration of the trabecular apparatus in the tibia in both CR BNO 1055- and E2- treated animals in comparison to castrated controls. These data indicate a specific effect of substances in CR BNO 1055, which inhibits osteoblast RANKL production. Thereby osteoclastogenesis and function are also inhibited, which may in part explain the antiosteoporotic effects of the CR Extract. In addition, the stimulation of Osteocalcin points to a stimulatory effect of CR BNO 1055 on bone formation. Thus, the effects of CR BNO 1055 and E2 differ in that E2 suppresses all osteoblast parameters and thereby also osteoclastogenesis, whereas CR BNO 1055 appears to inhibit osteoclastogenesis and function but simultaneously stimulates osteoblasts and thereby possibly osteogenesis.

  • Cimicifuga Racemosa Extract for the treatment of climacteric complaints
    Journal of Endocrinology and Reproduction, 2006
    Co-Authors: W Wuttke, Hubertus Jarry, Dana Seidlovawuttke
    Abstract:

    Cimicifuga Racemosa (CR) is widely used to treat climacteric complaints. These complaints, particularly hot flushes, are associated with over-activity of GnRH pulse generator in the hypothalamus, which is significantly reduced by E 2 . These effects can be ideally studied in ovariectomized (ovx) rats. In the present contribution we show that over-activity of GnRH pulse generator in the rat model is reduced by E 2 and by CR BNO 1055 as reflected in the reduced LH pulse amplitudes. This effect is not mediated by the pituitary because the Extract had no effect on LH and TSH secretion but significantly inhibited prolactin release from cultured pituitary cells indicating the presence of dopaminergic compounds. Both, E 2 and CR treatment of ovx rats had profound effects on the expression of ER-alpha and ER-beta genes in the medio-basal hypothalamus and the preoptic area and both the compounds stimulated tyrosine hydroxylase gene expression in the preoptic area. This hypothalamic site is the location of GnRH perikarya. It can, therefore, be concluded that catecholaminergic mechanisms are involved in the modality by which the E 2 and CR inhibit the over-activity of the GnRH pulse generator in ovx rats and in postmenopausal women.

  • Cimicifuga Racemosa Extract bno 1055 inhibits proliferation of the human prostate cancer cell line lncap
    Phytomedicine, 2005
    Co-Authors: Hubertus Jarry, Paul Thelen, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Extracts from black cohosh (Cimicifuga Racemosa, CR) exert an anti-proliferative action in human breast cancer cell cultures, which has been attributed to an anti-estrogenic effect. However, CR constituents do not bind to either of the known estrogen receptors. Thus, the anti-tumor effect of CR me be mediated by mechanisms not involving these receptors. Polycyclic aromatic hydrocarbons are toxic environmental pollutants, which indirectly act as anti-estrogens by activating the aryl hydrocarbon receptor (AhR). The AhR is widely expressed in mammalian tissues and tumors. A recent screening study demonstrated activation of the AhR by a variety of herbal Extracts, among others, CR. Since activation of the AhR causes inhibition of growth of prostate cancer cells, we addressed the question, whether CR may not only inhibit growth of breast cancer — but also of prostate cancer cells. In the AhR ligand assay, the CR Extract BNO 1055 reduced tracer binding to 71% of the control demonstrating interaction of constituents of this Extract with the receptor. Under basal as well as under estradiol- and dihydrotestosterone stimulated conditions, the CR Extract dose dependently inhibited proliferation of LNCaP cells. A significant reduction of cell growth was observed at a concentration as low as 50 ng/ml. Thus, it is demonstrated for the first time that CR compounds potently inhibit the growth of human prostate cancer cells in vitro. This anti-proliferative effect may be mediated via the AhR.

  • in vitro effects of the Cimicifuga Racemosa Extract bno 1055
    Maturitas, 2003
    Co-Authors: Hubertus Jarry, Maria Metten, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Objectives: Extracts of Black cohosh ( Cimicifuga Racemosa or CR) have been used for the treatment of climacteric complaints since decades. Efficacy, particularly concerning neurovegetative and psychic symptoms, has been proven in clinical trials. As active principle yet unknown substances with selective estrogen receptor modulator (SERM) activity are assumed. Recently, evidence arose that CR may also contain dopaminergic compounds, which may contribute to the therapeutic activity of the Extract. Methods: Two subtypes of the estrogen receptor (ERα and ERβ) are known. To examine, whether active substances of CR Extract BNO 1055 (which is contained in Klimadynon® and Menofem®) bind to either of the two estrogen receptors, subtype-specific estrogen receptor ligand-binding assays with recombinant ERα or ERβ were conducted. A ligand-binding assay with recombinant dopamine D 2 -receptor protein was employed to assess possible dopaminergic activity in the CR Extract BNO 1055. Results: While a displacement of radiolabeled estradiol from binding sites of a cytosol preparation from procine and human endometrium by CR Extract BNO 1055 was shown no such displacement was achieved when either ERα or ERβ protein was used as ligands for tracer. Dopaminergic activity in the CR Extract BNO 1055 could be demonstrated with the D 2 -receptor assay. A countercurrent chromatography resulted in a separation of estrogenic and dopaminergic activity in two distinct fractions. Conclusions: It is suggested that not yet identified substances in the CR Extract BNO 1055 bind to a yet unknown estrogen-binding site in the endometrium. Also, yet unknown dopaminergic compounds may contribute to the pharmacological profile of CR Extract BNO 1055.

  • pharmacology of Cimicifuga Racemosa Extract bno 1055 in rats bone fat and uterus
    Maturitas, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Volker Christoffel, Tamara Becker, W Wuttke
    Abstract:

    Abstract Objectives: Hormone replacement therapy (HRT) has therapeutic effects on climacteric complaints and prevents osteoporosis. Owing to the increased risks of breast cancer and cardiovascular diseases, patients look for alternatives. Cimicifuga Racemosa (CR) preparations might be an alternative, because they proved to reduce climacteric complaints as efficiently as conjugated estrogens without exerting estrogenic effects in the uterus. Whether CR has positive effects on bone and in fat tissue is currently unknown. Therefore, osteoprotective effects of the CR Extract BNO 1055 and an influence on fat tissue were studied in ovariectomized rats. Methods: Bone mineral density (BMD) of the tibia of ovariectomized (ovx) rats was determined by computer-assisted tomography (CT). CT scans of fat depots were perimetrically quantified. Bone turnover (osteocalcin, crosslaps) and lipocyte activity (leptin) were also determined. Uterine weights were measured and gene expression of estrogen-regulated uterine genes (IGF-1, ERβ) was determined by RT-PCR. Results: Treatment of the ovx rats over a period of 3 months with E 2 and the CR Extract BNO 1055 showed osteoprotective effects; both significantly reduced the loss of BMD in tibia. Serum osteocalcin levels were significantly reduced by both treatments, whereas only E 2 , but not BNO 1055, reduced serum crosslaps. A paratibial fat depot and serum leptin concentration were also significantly reduced. In contrast to E 2 , the CR Extract showed no effect on uterine weight and gene expression of E 2 -regulated genes. Conclusion: The CR Extract BNO 1055 exerted estrogenic effects in the bone (particularly in osteoblasts) and in fat tissue, but not in the uterus of ovx rats. The Extract appears to contain rat organ-specific selective estrogen receptor modulators (SERMs), and if these findings can be approved in human it may be an alternative to HRT.

Volker Christoffel - One of the best experts on this subject based on the ideXlab platform.

  • Reprint of Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy?
    Maturitas, 2008
    Co-Authors: Wolfgang Wuttke, Christoph Gorkow, Hubertus Jarry, Volker Christoffel, Tamara Becker, Alexander Schultens, Dana Seidlova-wuttke
    Abstract:

    Abstract Objectives: This review presents findings with clear statements from the literature as well as own results of effects of soy, red clover and their isoflavones as well as of the Cimicifuga Racemosa Extract BNO 1055. Experimental and clinical effects on climacteric complaints, osteoprotective effects, activity in the urogenital tract, and risks concerning cardiovascular diseases and mammary and endometrial tissue will be compared, also in comparison to classical hormone preparations. The question whether soy and red clover products and/or Cimicifuga Racemosa (CR) preparations are endocrine disrupters or may fulfill the criteria of the so-called phyto-SERMs will be discussed. Methods: Review of selected publications since 1980 and summary of unpublished own results of the authors. Results: Experimental and clinical evidences suggest that soy/red clover and their isoflavones do not fulfill the criteria of an ideal SERM. They appear to have mild osteoprotective effects but do not improve climacteric complaints. Furthermore, they seem to stimulate uterine growth and mammary epithelial proliferation. In ovariectomized rats, the CR Extract BNO 1055 showed many of the beneficial effects of 17b-estradiol, including effects in the brain/hypothalamus to reduce serum LH levels, effects in the bone to prevent osteoporosis and estrogenic effects in the urinary bladder. The CR Extract BNO 1055 had no uterotrophic effect. Conclusion: If clinical studies confirm these results, the Cimicifuga Racemosa preparation BNO 1055 would appear as an ideal SERM and may therefore be an alternative to hormone replacement therapy.

  • Cimicifuga Racemosa Extract bno 1055 inhibits proliferation of the human prostate cancer cell line lncap
    Phytomedicine, 2005
    Co-Authors: Hubertus Jarry, Paul Thelen, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Extracts from black cohosh (Cimicifuga Racemosa, CR) exert an anti-proliferative action in human breast cancer cell cultures, which has been attributed to an anti-estrogenic effect. However, CR constituents do not bind to either of the known estrogen receptors. Thus, the anti-tumor effect of CR me be mediated by mechanisms not involving these receptors. Polycyclic aromatic hydrocarbons are toxic environmental pollutants, which indirectly act as anti-estrogens by activating the aryl hydrocarbon receptor (AhR). The AhR is widely expressed in mammalian tissues and tumors. A recent screening study demonstrated activation of the AhR by a variety of herbal Extracts, among others, CR. Since activation of the AhR causes inhibition of growth of prostate cancer cells, we addressed the question, whether CR may not only inhibit growth of breast cancer — but also of prostate cancer cells. In the AhR ligand assay, the CR Extract BNO 1055 reduced tracer binding to 71% of the control demonstrating interaction of constituents of this Extract with the receptor. Under basal as well as under estradiol- and dihydrotestosterone stimulated conditions, the CR Extract dose dependently inhibited proliferation of LNCaP cells. A significant reduction of cell growth was observed at a concentration as low as 50 ng/ml. Thus, it is demonstrated for the first time that CR compounds potently inhibit the growth of human prostate cancer cells in vitro. This anti-proliferative effect may be mediated via the AhR.

  • evidence for selective estrogen receptor modulator activity in a black cohosh Cimicifuga Racemosa Extract comparison with estradiol 17beta
    European Journal of Endocrinology, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Barbara Spengler, Volker Christoffel, Tamara Becker, Oda Hesse, Wolfgang Wuttke
    Abstract:

    Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. 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-17b (E2) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E2 or the CR Extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E2 and the CR Extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E2 and partially by CR supplementation. Conclusions: These data confirm the concept that the CR Extract BNO 1055 contains as yet unidentified substances with SERM properties which act in the hypothalamo/pituitary unit and in the bone but not in the uterus.

  • in vitro effects of the Cimicifuga Racemosa Extract bno 1055
    Maturitas, 2003
    Co-Authors: Hubertus Jarry, Maria Metten, Barbara Spengler, Volker Christoffel, W Wuttke
    Abstract:

    Abstract Objectives: Extracts of Black cohosh ( Cimicifuga Racemosa or CR) have been used for the treatment of climacteric complaints since decades. Efficacy, particularly concerning neurovegetative and psychic symptoms, has been proven in clinical trials. As active principle yet unknown substances with selective estrogen receptor modulator (SERM) activity are assumed. Recently, evidence arose that CR may also contain dopaminergic compounds, which may contribute to the therapeutic activity of the Extract. Methods: Two subtypes of the estrogen receptor (ERα and ERβ) are known. To examine, whether active substances of CR Extract BNO 1055 (which is contained in Klimadynon® and Menofem®) bind to either of the two estrogen receptors, subtype-specific estrogen receptor ligand-binding assays with recombinant ERα or ERβ were conducted. A ligand-binding assay with recombinant dopamine D 2 -receptor protein was employed to assess possible dopaminergic activity in the CR Extract BNO 1055. Results: While a displacement of radiolabeled estradiol from binding sites of a cytosol preparation from procine and human endometrium by CR Extract BNO 1055 was shown no such displacement was achieved when either ERα or ERβ protein was used as ligands for tracer. Dopaminergic activity in the CR Extract BNO 1055 could be demonstrated with the D 2 -receptor assay. A countercurrent chromatography resulted in a separation of estrogenic and dopaminergic activity in two distinct fractions. Conclusions: It is suggested that not yet identified substances in the CR Extract BNO 1055 bind to a yet unknown estrogen-binding site in the endometrium. Also, yet unknown dopaminergic compounds may contribute to the pharmacological profile of CR Extract BNO 1055.

  • In vitro effects of the Cimicifuga Racemosa Extract BNO 1055.
    Maturitas, 2003
    Co-Authors: Hubertus Jarry, Maria Metten, Barbara Spengler, Volker Christoffel, Wolfgang Wuttke
    Abstract:

    Extracts of Black cohosh (Cimicifuga Racemosa or CR) have been used for the treatment of climacteric complaints since decades. Efficacy, particularly concerning neurovegetative and psychic symptoms, has been proven in clinical trials. As active principle yet unknown substances with selective estrogen receptor modulator (SERM) activity are assumed. Recently, evidence arose that CR may also contain dopaminergic compounds, which may contribute to the therapeutic activity of the Extract. Two subtypes of the estrogen receptor (ERalpha and ERbeta) are known. To examine, whether active substances of CR Extract BNO 1055 (which is contained in Klimadynon and Menofem) bind to either of the two estrogen receptors, subtype-specific estrogen receptor ligand-binding assays with recombinant ERalpha or ERbeta were conducted. A ligand-binding assay with recombinant dopamine D(2)-receptor protein was employed to assess possible dopaminergic activity in the CR Extract BNO 1055. While a displacement of radiolabeled estradiol from binding sites of a cytosol preparation from procine and human endometrium by CR Extract BNO 1055 was shown no such displacement was achieved when either ERalpha or ERbeta protein was used as ligands for tracer. Dopaminergic activity in the CR Extract BNO 1055 could be demonstrated with the D(2)-receptor assay. A countercurrent chromatography resulted in a separation of estrogenic and dopaminergic activity in two distinct fractions. It is suggested that not yet identified substances in the CR Extract BNO 1055 bind to a yet unknown estrogen-binding site in the endometrium. Also, yet unknown dopaminergic compounds may contribute to the pharmacological profile of CR Extract BNO 1055.

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  • Cimicifuga Racemosa Extract for the treatment of climacteric complaints
    Journal of Endocrinology and Reproduction, 2006
    Co-Authors: W Wuttke, Hubertus Jarry, Dana Seidlovawuttke
    Abstract:

    Cimicifuga Racemosa (CR) is widely used to treat climacteric complaints. These complaints, particularly hot flushes, are associated with over-activity of GnRH pulse generator in the hypothalamus, which is significantly reduced by E 2 . These effects can be ideally studied in ovariectomized (ovx) rats. In the present contribution we show that over-activity of GnRH pulse generator in the rat model is reduced by E 2 and by CR BNO 1055 as reflected in the reduced LH pulse amplitudes. This effect is not mediated by the pituitary because the Extract had no effect on LH and TSH secretion but significantly inhibited prolactin release from cultured pituitary cells indicating the presence of dopaminergic compounds. Both, E 2 and CR treatment of ovx rats had profound effects on the expression of ER-alpha and ER-beta genes in the medio-basal hypothalamus and the preoptic area and both the compounds stimulated tyrosine hydroxylase gene expression in the preoptic area. This hypothalamic site is the location of GnRH perikarya. It can, therefore, be concluded that catecholaminergic mechanisms are involved in the modality by which the E 2 and CR inhibit the over-activity of the GnRH pulse generator in ovx rats and in postmenopausal women.

  • inhibitory effects of a black cohosh Cimicifuga Racemosa Extract on prostate cancer
    Planta Medica, 2006
    Co-Authors: Dana Seidlovawuttke, Paul Thelen, Wolfgang Wuttke
    Abstract:

    The Cimicifuga Racemosa Extract BNO 1055 (CR) inhibits proliferation of human prostate cancer-derived LNCaP cells. Therefore, we tested the capability of this Extract to inhibit formation and/or proliferation of tumors induced by subcutaneous (s. c.) inoculation of LNCaP cells in immunodeficient nu/nu mice. After inoculation of 1 million cells, 12 of 18 animals developed solid tumors while tumor development was seen in only 5 of 18 CR-treated animals and the size of the latter at termination of the experiments 10 weeks after inoculation was significantly smaller than in the control animals. Upon histological inspection, the amount of tumor tissue in the control animals was significantly larger than in the CR-treated animals while in the latter connective tissue was predominant. The CR treatment did not affect serum testosterone levels significantly regardless of whether the animals developed tumors or not. It is concluded that compounds in CR inhibit tumor development, proliferation and dignity of the tumors following s.c. inoculation of LNCaP cells. Hence, the CR Extract may prove to be efficient in preventing and treatment of prostate cancer.

  • evidence for selective estrogen receptor modulator activity in a black cohosh Cimicifuga Racemosa Extract comparison with estradiol 17beta
    European Journal of Endocrinology, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Barbara Spengler, Volker Christoffel, Tamara Becker, Oda Hesse, Wolfgang Wuttke
    Abstract:

    Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. 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-17b (E2) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E2 or the CR Extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E2 and the CR Extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E2 and partially by CR supplementation. Conclusions: These data confirm the concept that the CR Extract BNO 1055 contains as yet unidentified substances with SERM properties which act in the hypothalamo/pituitary unit and in the bone but not in the uterus.

  • pharmacology of Cimicifuga Racemosa Extract bno 1055 in rats bone fat and uterus
    Maturitas, 2003
    Co-Authors: Dana Seidlovawuttke, Hubertus Jarry, Volker Christoffel, Tamara Becker, W Wuttke
    Abstract:

    Abstract Objectives: Hormone replacement therapy (HRT) has therapeutic effects on climacteric complaints and prevents osteoporosis. Owing to the increased risks of breast cancer and cardiovascular diseases, patients look for alternatives. Cimicifuga Racemosa (CR) preparations might be an alternative, because they proved to reduce climacteric complaints as efficiently as conjugated estrogens without exerting estrogenic effects in the uterus. Whether CR has positive effects on bone and in fat tissue is currently unknown. Therefore, osteoprotective effects of the CR Extract BNO 1055 and an influence on fat tissue were studied in ovariectomized rats. Methods: Bone mineral density (BMD) of the tibia of ovariectomized (ovx) rats was determined by computer-assisted tomography (CT). CT scans of fat depots were perimetrically quantified. Bone turnover (osteocalcin, crosslaps) and lipocyte activity (leptin) were also determined. Uterine weights were measured and gene expression of estrogen-regulated uterine genes (IGF-1, ERβ) was determined by RT-PCR. Results: Treatment of the ovx rats over a period of 3 months with E 2 and the CR Extract BNO 1055 showed osteoprotective effects; both significantly reduced the loss of BMD in tibia. Serum osteocalcin levels were significantly reduced by both treatments, whereas only E 2 , but not BNO 1055, reduced serum crosslaps. A paratibial fat depot and serum leptin concentration were also significantly reduced. In contrast to E 2 , the CR Extract showed no effect on uterine weight and gene expression of E 2 -regulated genes. Conclusion: The CR Extract BNO 1055 exerted estrogenic effects in the bone (particularly in osteoblasts) and in fat tissue, but not in the uterus of ovx rats. The Extract appears to contain rat organ-specific selective estrogen receptor modulators (SERMs), and if these findings can be approved in human it may be an alternative to HRT.