Download Black cohosh

FEATURE
By WENDELL L. COMBEST, Ph.D., Associate Professor of Pharmacology,
Department of Biopharmaceutical Sciences, Shenandoah University School of
Pharmacy, Winchester, VA.
lack cohosh (Cimicifuga racemosa), of the family
Ranunculaceae, is a hardy perennial indigenous to
the eastern U.S. but widely cultivated as an attractive garden ornamental. The plant can grow to a height of 8
feet. It has large, irregular, tooth-edged leaves and a flower
stalk supporting tall plumes of fragrant white flowers, which
bloom from June through September. It prefers rich sandy
soil, and is most often found growing in woodland habitats.
The name “cohosh” is derived from an Algonquian word
meaning “rough,” which describes the knotty texture of the
rhizome.1 The rhizomes are dark brownish-black in colour,
hence the name black cohosh. The roots and rhizome – which
have a bitter, acrid taste – are the medicinally useful part of
the plant. The Latin name Cimicifuga means “bug-repellent,”
reflecting one of its popular uses. There are 15 species
comprising the genus Cimicifuga, and various species in
Europe are referred to by the common name “bugbane” for
its purported insect-repelling activity.
B
CHEMICAL COMPOSITION
AND ACTIVE CONSTITUENTS
benefit of black cohosh is in the treatment of postmenopausal
symptoms. Eight clinical trials have been published since the
early 1980s; most of the studies have been carried out in
Germany. The German Commission E approves black cohosh
for “premenstrual discomfort, dysmenorrhea, or menopausal
neurovegetative ailments.” One of the first studies involved
36 postmenopausal women treated with Remifemin (an alcoholic extract of black cohosh roots).4 Remifemin is a
brand-name product (manufactured by Schaper and
Brummer in German) and is standardized to contain triterpene glycoside, usually 1 mg of 27-deoxyacteine per tablet.
Treatment for 12 weeks resulted in a decrease in menopausal
symptoms, with no reported side effects. These results were
supported by a similar study published the next year.5 This
12-week study of 50 postmenopausal women assessed symptoms utilizing the Profile of Mood States (POMS) and Clinical
Global Impression Scale (CGI).
Remifemin treatment resulted in
a significant improvement in
both the POMS and CGI scales.
The only side effect noted was
mild gastrointestinal disturbances in four patients.
This popular native American
herb is used worldwide to treat
menopausal symptoms.
The rhizomes and roots
contain triterpene glycosides
actein, cimicifugoside, and 27deoxyactein, which are
considered the main active
constituents.2 Eight newly described glycosides have recently
been isolated and characterized from the Japanese species
Cimicifuga simplex.3 Other constituents include the alkaloid
n-methylcytisine along with many other related quinolizidine
alkaloids, the isoflavone formononetin, and the phenolic acids
isoferulic and salicylic acids, as well as various tannins.
Several studies have
compared Remifemin to conventional treatment of
menopausal symptoms with various forms of estrogen or
diazepam (Valuim). One study compared the efficacy of
Remifemin in treating menopausal symptoms to hormone
treatment or therapy with a psychotropic drug in 60 patients.6
Remifemin (two 1 mg tablets twice daily), conjugated estro-
MEDICINAL USES AND PHARMACOLOGY
gens (Premarin, 0.625 mg/day) or diazepam (Valium, 2
Native Americans used the roots and rhizomes for a variety of ailments, including menstrual cramps and pain
associated with labour and delivery. Eclectic physicians in the
U.S during the 1800s used black cohosh to treat uterine difficulties, stimulate menstrual flow, and reduce discomforts
during labour. It was one of the main ingredients in Lydia
Pinkham’s Vegetable Compound, which was one of the most
popular patent remedies for “women’s complaints” during
this period. Black cohosh has been used in Germany since the
mid-1950s for treatment of menopausal symptoms.
Clinical Studies: The strongest evidence for a clinical
mg/day) was given for three months. Remifemin was found
10
to be more effective than Premarin or Valium in relieving the
depressive mood and anxiety associated with menopause.
These results were further supported in a study involving 80
patients who were treated for 12 weeks with either
Remifemin (8 mg daily), conjugated estrogens (0.625 mg
daily) or placebo.7 Remifemin was more effective in reducing
anxiety, atrophic vaginitis, and the frequency of hot flashes. In
another clinical trial, 60 women who had hysterectomies with
at least one remaining ovary were given either estriol (1 mg
COMMUNICATION NOVEMBER/DECEMBER 2000
daily), conjugated estrogens (1.25 mg daily), estrogen-gesta-
in ovariectomized rats. Extracts from two Cimicifuga species
daily).8
(Cimicifuga heracleifolia and Cimicifuga dahoric) have been
gen (Trisequens, 1 tablet daily), or Remifemin (8 mg
Menopausal symptoms, such as hot flashes and nervousness,
used extensively as antipyretic, analgesic, and anti-inflamma-
were significantly reduced by all treatments, with no differ-
tory agents in Japanese oral medicine. Ferulic acid (FA) and
ences noted between the various therapies. Remifemin’s
isoferulic acid (IFA) were found to be active anti-inflamma-
ability to improve menopausal symptoms was compared to
tory compounds in methanol extracts of the roots of these
previous therapy with estrogen replacement or psychoactive
species.14 These compounds were found to inhibit interleukin-
drugs in 629 female
patients.9
Remifemin treatment for 6 – 8
8 production in response to influenza virus infections in vitro
weeks improved menopausal symptoms in more than 80% of
and in vivo. The in vitro studies were done in a murine
women. The only side effect reported was mild GI distress in
macrophage cell line infected with influenza virus. The in
7% of the patients. One study examined the effectiveness of
vivo study involved injecting mice with the influenza virus
Remifemin in 50 women who had discontinued estrogen
with and without prior oral administration (5
Remifemin was administered for 6
mg/mouse/day) of Cimicifuga extracts, 0.5 mg/mouse/day
months. Effectiveness was evaluated by a gynecologist as
of FA, or 0.125 mg/mouse/day of IFA. The three treatments
very good in 21 patients and good in 20 patients, with little
reduced IL-8 levels in bronchoalveolar lavage obtained two
effect seen in 9 patients.
days after infection. These results indicate that at least two
replacement
therapy.10
A double-blind trial in 10 postmenopausal women, in
which half were treated with Remifemin (8 mg daily) for 8
weeks, resulted in significant improvements in menopausal
components in Cimicifuga may be responsible for the
extract’s analgesic and anti-inflammatory activity.
Limited data is available for additional effects of black
symptoms for those receiving Remifemin.11 Blood levels of
cohosh root extracts. The steroidal triterpene derivative action
luteinizing hormone (LH), but not follicle stimulating
was shown to lower blood pressure in rabbits and cats, but
hormone (FSH), were significantly reduced in the treatment
not dogs.15 This hypotensive effect has not been demonstrated
group. Many of the symptoms of menopause are believed to
in humans. Root extracts from Cimicifuga foetida and
result from elevated blood levels of LH.
Cimicifuga heraclefolia species were recently shown to inhibit
Animal and In Vitro Studies: The effects of an orally
parathyroid hormone-induced bone reabsorption in tissue
administered ethanolic extract of black cohosh rhizomes on
culture and in ovariectomized rats.16 Isopropanolic extracts of
uterine growth in immature mice and on vaginal cornification
Cimicifuga racemosa were shown to inhibit the proliferation
in ovariectomized rats were
investigated.12
Results revealed
of estrogen-dependent breast cancer cell lines in a dose-
no signs of estrogenic growth of uterine or vaginal tissues.
dependent manner.17
This study suggests that the beneficial effects of black cohosh
SIDE EFFECTS AND TOXICITY
are not due to a classic estrogen trophic effect in these tissues.
The FDA lists black cohosh as an herb of “undefined
In another study, lipophilic extracts of black cohosh roots
safety.” The German Commission E notes no contraindica-
were subjected to gel-exclusion chromatography, with various
tions, with occasional gastric upsets likely due to the high
fractions tested for their ability to reduce LH secretion in
tannin content. Because of the lack of long-term toxicity stud-
ovariectomized rats and to compete with 17-b-estradiol bind-
ies, its use is recommended for no more than six months.
ing sites in uterine tissue.11 Several fractions had LH-reducing
Black cohosh is contraindicated in pregnancy, and large doses
activity, whereas others were able to compete for the estrogen
could result in miscarriage.18 No reports of adverse effects on
receptor. The results of this study suggest the presence of
lactation or in nursing children have been made. No drug
multiple constituents in black cohosh roots that could act
interactions have been noted. Remifemin has often been used
synergistically to bring about a coordinated pharmacological
in conjunction with estrogen replacement therapy, with no
response.
reported adverse effects.
The above study supports an earlier investigation of chromatographically separated fractions from methanol extracts
of black cohosh rhizomes.13 At least three fractions were
found that could either decrease LH blood levels in ovariectomized rats or compete with estrogen in an in vitro estrogen
receptor assay. One of the isolated fractions was further characterized and found to include the isoflavon formononetine.
Isolated formononetine was shown to be a competitor for
estrogen in the receptor assay, but failed to decrease LH levels
COMMUNICATION NOVEMBER/DECEMBER 2000
DOSAGE FORMS AND RECOMMENDATIONS
All clinical studies (mostly Germany-based) have utilized
the alcoholic extract of Cimicifuga racemosa Remifemin.
Nearly 10 million one-month supplies of Remifemin were sold
in Australia, Germany, and the United States in 1996.20 Clinical
trial results indicate that dosages of 4-8 mg per day were effective in reducing many of the symptoms of menopause. ■
References available on request to MSP.
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