What is Black Cohosh ?Black Cohosh - A Lady's Herb.
Content:
- .Botanical Data of Black Cohosh.
- .Narrative History of Black cohosh.
- .Application and Uses of Black cohosh.
- .Phytochemicals,constituents and functional mechanism of Black Cohosh.
- .Historical Development of Black Cohosh.
- .Modern Use and application of Black cohosh.
- .Black Cohosh Physiology.
- .Clinical studies of Black Cohosh.
- .Dosage and other comments.
- .Skunk Bugbane and Application.
- .How Search engine think about black cohosh.
Clinical studies of Black Cohosh.
Preclinical Studies:
Cardiovascular and Circulatory Functions:
Actein is hypotensive in cats and rabbits, but not consistently in dogs (Newall et al., 1996; Duke, 1985). Newall et al. (1996) cited a study showing that actein causes peripheral vasodilation and an increase in peripheral blood flow in patients diagnosed with peripheral arterial disease; their blood pressure (normal or hypertensive) was unchanged by this treatment.
Endocrine and Hormonal Functions:
Hypothalamic and Pituitary Functions:
An alcoholic extract of black cohosh root administered to ovariectomized rats as part of their diet at (1/3 the human dose equivalent for 3 weeks) was reported to increase uterine weight and raise serum ceruloplasmin levels, both results indicative of an estrogenic activity (Eagon, 1999; Eagon et al., 1997). In evaluating the hypothalamic/pituitary response of the test animals, Eagon et al. (1998) quantified luteinizing hormone (LH) levels. Black cohosh extract produced a significant (p:less than 0.05) decrease of 25%.
Reproductive Hormone Interactions:
Foster (1999) refers to a study by Freudenstein and Bodinet in which an extract of black cohosh rhizome was shown not to stimulate proliferation of estrogen receptor-positive MCF-7 breast cancer cells. The extract was also found to increase the growth-inhibitory effect of tamoxifen on the cells. The authors concluded that extracts of the herb can be safely taken by patients who are susceptible to breast cancer (See Contraindications).
Zava et al. (1998) reported only little estrogenic and estrogen receptor-binding bioactivity from a 50% ethanol/water extract of black cohosh in vitro. In further contrasting results, studies in rats (Eagon et al., 1997, 1998) as well as menopausal women (Jarry and Harnischfeger, 1985a) have demonstrated reduced luteinizing hormone (LH) levels from black cohosh. However, a study by Einer-Jensen et al. (1996) indicated a lack of estrogenic effects in mice and rats, and Liske (1998) (See Clinical Studies) states that no significant decrease in LH (or other hormonal changes), or other measures of estrogenic activity (e.g., increased vaginal epithelium thickness), were attributable to the black cohosh preparation Remifemin, at least with the new lower dose now recommended by the manufacturers (Schaper and Brummer GmbH, 1997).
Black cohosh prevented the stimulation of estrogen-dependent cancer cells when estrogen was added in vitro. Tamoxifen and black cohosh may act synergistically to block estrogenic proliferation of breast cancer cells, because the combined inhibitory effect was greater than the sum of the effect of each substance alone (Nesselhut et al., 1998). Isopropanolic aqueous extracts of black cohosh inhibit in vitro proliferation of estrogen-dependent breast cancer cell lines in a dose-dependent manner. This activity has been interpreted as an estrogen-receptor blockade (Nesselhut et al., 1993).
Constituents of black cohosh rhizome can bind to estrogen receptors in rat uteri and pituitary glands, but some controversy exists as to what estrogenic effects result from the binding of these sites. Duker et al. (1991) characterized pharmacological responses to various chromatographically separated fractions of black cohosh lipophilic extract in ovariectomized rats. Fractionation studies using ovariectomized rats resulted in the isolation of 3 endocrinologically-active fractions: fraction I inhibited luteinizing hormone (LH) secretion but did not bind to estrogen receptors; fractions IV to VI were active in both assays, while fraction VIII displayed the most potency in estrogen receptor assays, without suppressing LH secretion after chronic treatment. This fraction did inhibit LH after a single acute injection; single injections of estradiol showed a similar activity profile. The authors explained that the lack of an effect on follicle stimulating hormone (FSH) inhibition is due to FSH secretion being under the control of steroids plus inhibin, while LH secretion is mediated only by gonadal steroids. The authors speculated that fraction VIII, which acutely but not chronically inhibited LH secretion, may contain estrogenically-active compounds which are rapidly metabolized so that only a transient suppressive effect on LH secretion is produced. This may provide a rationale for the demonstrated clinical efficacy of black cohosh in the treatment of menopausal hot flashes; the pulsatile release of LH is inhibited, but overall LH levels are not suppressed. At present this explanation is speculative. Fraction I, which was non-estrogenic but did suppress LH secretion, may have contained alpha-2 agonists similar to clonidine, which suppresses LH secretion without binding to the estrogen receptor (Duker et al., 1991; Jarry and Harnischfeger, 1985).
Studies on the Chinese traditional medicine shengma (Actaea = Cimicifuga spp.) showed that injections of the extract increased uterine weight and "established the estrus cycles" of immature adolescent and climacteric female rats. In adolescent rats, ovarian weight and the number of corpora lutea increased (Chang and But, 1986). "Shengma" refers to several species of black cohosh, viz., A. heracleifolia Kom., A. dahurica (Turcz.) Maxim., or A. foetida L. It is not clear from the original reference which of these species was used in these experiments, or whether a mixture was used.
Integumentary, Muscular, and Skeletal Functions:
Osteoporosis
Two recent studies of other Actaea species (A. foetida and A. heracleifolia) demonstrated inhibition of parathyroid hormone-induced bone resorption in tissue culture (Li et al., 1996a), and in ovariectomized rats (Li et al., 1995). This anti-osteoporotic effect has yet to be discussed in the literature in terms of estrogen receptor-binding activity of black cohosh, although mention was made of a positive influence on osteoporotic states (Murray, 1997).
Li et al. (1996/97) reported a significant (approximately 10%) increase in spinal bone mineral density in ovariectomized rats fed a low calcium diet following administration of ethyl acetate-soluble fractions of Actaea heracleifolia and Actaea foetida (100 mg/kg/day, p.o.). The fractions prevented osteoporosis-like bone loss. Four triterpenoids derived from these species also showed calcium level decreasing activity in low calcium diet rats (25 mg/kg, p.o.), implicating them as the active constituents.
Clinical Studies for hot flashes:
There have been 3 double-blind RCT's of black cohosh for hot flashes. All have tested a formulation called Remifemin which is manufactured in Germany but widely available in the United States.
Lehmann et al. (1988) found it to be equal in efficacy to estrogen, although the study's small size (n=60) limited its power to detect clinically significant differences.
Stoll et al (1987) randomized 80 women to black cohosh, estrogen, or placebo. Women who took black cohosh had fewer hot flashes, although the trial's methodology is called into question by the fact that women who took estrogen did not do better than those who took placebo.
Jacobson et al (2001) compared black cohosh to placebo in women with breast cancer, the majority of whom were also taking tamoxifen. Symptoms of hot flashes were no different between the two groups.
There is no data to support the use of black cohosh for its other purposes.
Neurological, Psychological, and Behavioral Functions:
Receptor and Neurotransmitter Mediated Functions
Analgesic, hypothermic and antipyretic effects have also been documented for Asian species (Sakuri and Nagai, 1996; Chang and But, 1986). Other pharmacological actions are reported for Actaea species known as shengma, as discussed in Chang and But (1986). Experimentally-induced convulsions in mice were reportedly suppressed by an alcoholic extract of A. dahurica.
Shengma (Actaea = Cimicifuga species) binds to serotonin (5HT1A) receptors (Liao et al., 1995) in vitro, and displays serotonin-blocking activities in animal studies (Yoo et al., 1995). Shengma species, A. dahurica rhizome tincture, and cimifugin are all reported to have sedative effects (Chang and But, 1986).
Reproductive Functions
Pregnancy and Labor Disorders:
Black cohosh has a documented uterine stimulant effect and can induce labor, according to a NAPRALERT summary (1997). Although extensively used by the Eclectic medical doctors of North America for specific conditions of pregnancy, labor and postpartum, there are no recent studies clarifying the pharmacological effects of black cohosh during pregnancy and labor. Studies from the 1920s showed that black cohosh stimulated the non-pregnant uterus of the guinea pig and cat, but depressed the pregnant uterus. The resinous cimicifugin had no effect on isolated intestine or uterus of animals (Brinker, 1996). Shengma species inhibited smooth muscle contraction of isolated intestinal tissue strips and pregnant uterine tissue, but failed to stimulate nonpregnant uterus and urinary bladder tissue strips (Chang and But, 1986).
Immune Functions; Inflammation and Disease
Cancer
Cytotoxicity
Weak cytotoxic activity against cultured HeLa cells has been reported (NAPRALERT, 1997).
Infectious Diseases
Microbial Infections
Black cohosh extracts are mostly without antibacterial, antifungal, or antiviral activity, although Staphylococcus aureus is the exception, according to NAPRALERT (1997). For Shengma species, antimicrobial activity was found only in vitro (Chang and But, 1986).
Inflammatory Response:
Extracts of shengma species may have anti-inflammatory activity (Hirabayashi et al., 1995; Sakurai and Nagai, 1996). Ferulic and isoferulic acid were believed to be at least partly responsible for these anti-inflammatory effects. Anti-inflammatory activity in agar- or dextran-induced paw edema in rats has been demonstrated for ferulic acid, Actaea dahurica, and Actaea simplex when administered by the intragastric route (Chang and But, 1986).
Today in Germany, black cohosh preparations are used in the treatment of menopause to improve symptoms such as hot flashes, depression and sleep disturbance. In 1985, German researchers found that black cohosh produced an effect on serum concentrations of pituitary hormone levels, including a significant and selective reduction of luteinizing hormone (while not significantly effecting levels of prolactin and follicle stimulating hormone). Hot flashes have been linked to a significant spike in the release of luteinizing hormone. The study provided a way to measure the endocrinological, particularly estrogenic effects, of black cohosh. A follow-up study failed to identify a single chemical component responsible for the luteinizing hormone suppressing activity, leading researchers to believe that synergistic effects of several chemical fractions were involved in the biological activity, competing with estradiol for binding sites on receptor proteins.
Reproductive Disorders:
Menopause:
An open study was conducted with 60 female patients under 40 years of age who had ovarian functional deficits following hysterectomy and at least one functional ovary remaining (Lehmann-Willenbrock and Riedel, 1988). One group received Remifemin? tablets (two 1-mg tablets, twice a day), a second group received estriol (one mg daily), and a third group received conjugated estrogens (1.25 mg/day); a fourth group received a combination of estrogen-gestagen (dose not specified). Evaluation criteria were the Kupperman Menopause Index, assay of serum FSH and LH levels, and evaluation of trophic disturbances in the genitals. All forms of therapy resulted in similar positive responses, with no significant differences between the 4 groups. There was improvement in the profile of complaints of post-operative ovarian functional deficits, significant declines in the Kupperman Menopause Index, and a moderate and insignificant decline in serum gonadotropin concentration.
A randomized, double-blind study was conducted with 80 female volunteers with menopausal symptoms (Stoll, 1987). Patients received Remifemin? (2 mg twice a day), or conjugated estrogens (0.625 mg) or placebo for 12 weeks. Patients treated with Remifemin? showed a significant increase in proliferation of vaginal epithelium compared to those on estrogens and placebo, or significant improvements of somatic and psychological parameters (Kupperman Menopause Index, Hamilton Anxiety Scale) compared to estrogen or placebo. No clear improvements were seen in the placebo group.
The makers of Remifemin (Schaper and Brummer GmbH, 1997) describe a multi-center controlled, randomized, double-blind clinical study of 152 women (ages 43-60) with neurovegetative climacteric complaints in pre- or postmenopause. All patients entering the study had a Kupperman Menopause Index of 20, indicating that they all suffered at least a moderate degree of menopausal complaints. No placebo was used in the experimental design. Instead, the patients were administered one of two doses (either two tablets or one tablet twice daily for 3 months) according to a double-blind, randomized protocol. Examination took place before treatment commenced, at two, 4, and 8 weeks, and at the conclusion of the study. Efficacy was measured using the Kupperman Menopause Index, Self-Assessment Depression Scale, the Clinical Global Impression scale, vaginal cytology indexes, and for hormone status, tests were made for luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta-estradiol (E2), prolactin, and sex hormone binding globulin (SHBG) levels. A summary of outcomes showed a statistically significant decrease in the Kupperman Menopause Index and Self-Assessment Depression Scale with Remifemin at both dosage levels. Efficacy was rated as good or very good by both doctors and patients in about 80% of the cases. The treatments at both dosage ranges were rated as well-tolerated by 95% of the women, and at 92% by their doctors. The company reported "no conspicuous changes" in vaginal cytology parameters, nor in the course of hormone concentrations for treatments at both dosage levels. Although no details are given on adverse effects, no evidence of serious adverse events or clinical toxicological effects were found (Schaper and Brummer GmbH, 1997).
Duker et al. (1991) investigated the effect of a standardized Remifemin ethanolic extract (4 mg twice daily for 8 weeks) on LH and FSH secretion in 110 menopausal women who had received no previous hormonal therapy. Hot flashes are the most common climacteric symptom in menopause, and are closely related to pulsatile LH release. After 8 weeks, LH but not FSH levels (by radioimmunoassay) were significantly reduced in patients receiving Remifemin, but not in those given placebo; FSH levels were similar in both groups.
A 6-month open study was conducted on 50 female patients with severe menopausal symptoms, who were converted from an estrogen injection regime to oral Remifemin (two 1-mg tablets twice daily), with additional hormonal injections given in cases of severe complaints (Peth, 1987). Over the course of the study, clear improvements were observed in symptoms as measured by the Menopausal Index (reduction from 17.6 to 9.2, p less than 0.001). Over half (56%) of the patients required no further hormone injections; additional hormone injections were needed in only 18% of the patients. Side effects were minimal and well-tolerated and 82% of the patients reported the effects of the Remifemin therapy as good or very good.
An open comparative study was conducted on 60 female patients being treated for menopausal symptoms over 12 weeks (Warnecke, 1985). Patients received Remifemin (40 drops twice daily), or conjugated estrogens (0.625 mg/day) or diazepam (2 mg/day). Patients showed similar cytologic responses to Remifemin and estrogens as measured by proliferation and maturation of vaginal epithelial cells. No cytological changes were observed in patients under diazepam therapy. All 3 forms of therapy showed comparable positive responses on neurovegetative and psychological symptoms, as measured by the Self-Assessment Depression Scale (SDS), the Hamilton Anxiety Scale (HAMA), and the Clinical Global Impression scale.
Two open studies were carried out on 50 women (Vorberg, 1984) and 36 women (Daiber, 1983). All had menopausal complaints, and hormone therapy had been either contraindicated by the patients or refused. Patients received 40 drops, twice daily for 3 months (note: this dose corresponds to 80 mg/day of herbal drug, or 4 standardized tablets containing a total of 4 mg triterpene glycosides, calculated as 27-deoxyactein). Responses were measured using the Kupperman Menopause Index, the Clinical Global Impression scale, and the Profile of Mood States. Patients showed significant decreases in the Kupperman Menopause Index after 12 weeks of therapy, positive responses in the Clinical Global Impression scale, and improvements in psychological symptoms, including decreases in weariness, despondency and ill-humor, and increased motivation and positive mood.
An open multi-center, multi-clinic, retrospective study was published in Germany in 1982. In total, 131 general practitioners provided data on 629 female patients with menopausal complaints. Some of the patients (n=327) had received no previous treatment, 204 women had been previously treated with hormones, 35 had received psychopharmaceutical treatments, 11 had been treated with a combination of psychopharmaceuticals and hormone therapy, and no specific pretreatment data was available for 12 subjects. Clear improvements in neurovegetative complaints (hot flashes, profuse perspiration, headache, vertigo, heart palpitation, ringing in the ears) and psychological disturbances (nervousness, irritability, sleep disturbances, depressive moods) were experienced by approximately 80% of the patients after 4 weeks of therapy. After 6-8 weeks, all symptoms abated in approximately 40% to 50% of the patients, and were markedly reduced or improved in an additional 30% to 40%. Overall improvement rates (abolished or ameliorated symptoms) ranged from 76% to 93% of patients. The Remifemin? dosage regime (40 drops of Remifemin? standardized extract twice daily for 6-8 weeks) lacked side effects, or had only minor side effects in 93% of the patients (Foster, 1999).
A recent product surveillance study of 911 post-, pre- and peri-menopausal women with psychovegetative complaints reported putative synergistic effects for the combination of black cohosh (A. racemosa) and St. John's wort (Hypericum perforatum) standardized extracts in the management of psychological symptoms (Liske et al., 1997).
Recent clinical studies have shed further light on the herb's effects. A 1982 an open multi-center German clinical study involving data on 629 patients from 131 general practitioners and gynecologists was published. The researchers found that after six to eight weeks of treatment, 80 percent of patients had beneficial effects. In over 49 percent of volunteers there was dramatic relief in reduction of hot flashes, sweating, headache, vertigo, palpitation and tinnitus, while over 39 percent reported significant reductions of these symptoms, along with a lessening of nervousness, irritability and depression. Side effects (unspecified gastrointestinal problems) were reported for seven percent of the women. None of the side effects were serious enough to discontinue treatment.
A 1987 German double blind study compared estrogen replacement therapy with black cohosh for three months in eighty women. Thirty received a black cohosh extract (8 mg per day), 30 received black cohosh, and 20 volunteers received placebo. The black cohosh preparation was well-tolerated and produced significant improvement in the test parameters, which included menopausal symptoms as measured by the Kupperman Menopausal Index, depressive symptoms as measured by the Hamilton Anxiety Scale, as well as its effect on vaginal epithelium cells. The author concluded that black cohosh not only produced safe and efficacious results, but compared to estrogen replacement therapy, is suitable as a treatment of choice in menopausal symptoms.
In 1991 German research group conducted a study involving 110 menopausal women. They demonstrated for the first time in a clinical trial that the extract selectively suppresses luteinizing hormone secretion in menopausal women, and further confirms an estrogenic effect of the alcoholic fractions of black cohosh root.
These limited clinical studies provide encouraging results setting the stage for further, larger scale controlled clinical studies in the future.
Clinical studies exist to support the primary application of black cohosh for the treatment of perimenopausal symptoms such as hot flash, headache, vertigo, heart palpitations, ringing in the ears, and associated psychological symptoms, including irritability, sleep disturbances, and depressive moods. Black cohosh extract has also been used successfully in women under 40 for treatment of hormonal insufficiencies resulting from ovariectomy/hysterectomy. Treatment requires at least eight weeks to alleviate symptoms. Clinical studies have ranged in length from 8 weeks to as long as 6 months.
Reference:
1.What is Black Cohosh ?Black Cohosh - A Lady's Herb.
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