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Herbs: Cimicifuga aka Actea racemosa



Taxonomy keeps changing: Linnaeus put it in Actaea genus, Nuttall later reclassfied to Cimicifuga based on dry follicle fruits, but more recent data has recategorized it back to genus Actaea. My prof still calls it Cimicifuga out of habit. Blue cohosh (Caulophyllum thalictroides) is another genus entirely.

History: Long used in treatment of gynecological and menopausal complaints, well known in German literature.

FAMILY: Ranunculaceae
COMMON NAMES: black cohosh, black bugbane, snakeroot, fairy candle, black snakeroot, bugwort, rattleroot, rattletop, rattleweed, and macrotys

HABIT
Woodland and meadow herbaceous perennial, native to eastern North America from southern Ontario south to central Georgia and west to Missouri and Arkansas.

DESCRIPTION
Insects avoid it. Large, tripinnately compound glabrous leaves from underground rhizome, basal leaves up to 1m long with coarsely toothed edge. Flowering white in late spring early summer, racemes up to 50cm long wihtout petals or sepals. Distinct sweet/unpleasant smell. Fruit is dry follicle 5-10mm long containing several seeds. Needs moist soil, does not tolerate heat/dryness.

USES
uterine complaints such as poor tone, menstrual cramps, and postmenopausal vaginal dryness
premenstrual tension, hot flashes
bone building: treatment and prevention of osteoporosis
control sx while weaning from H.R.T.
reducing menopausal symptoms following ovarian surgery
treatment of "deep dark depression" per Dr Frances
Native Americans use it to tx sore throats, kidney problems, and depression
has been used as an abortifacient
malaise, kidney disorders, malaria, rheumatism, colds, cough,
constipation, hives, backache, to induce lactation
in 19th-century America used as home remedy for rheumatism and fever, a diuretic, and to bring on menstruation

Black cohosh was extremely popular among a group of alternative practitioners who called black cohosh "macrotys" and prescribed it for rheumatism, lung conditions, neurological conditions, and conditions that affected women's reproductive organs (including menstrual problems, inflammation of the uterus or ovaries, infertility, threatened miscarriage, and relief of labor pains).

ACTIONS
binds serotonin receptors with high affinity
stimulates osteoblasts
stimulates endometrium??
increases blood flow to pelvic area??
mild estrogenic effect due to the binding of isoflavone to estrogen receptors??
decreases LH output by the anterior pituitary-->estrogenic effect??
no estrogen-like effects in estrogen sensitive breast cancer cells
(not contraindicated in breast cancer patients)
noted to inhibit the cell proliferating effects of actual estrogens

works on opiate receptors: Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Because the opiate system in the brain is intimately associated with mood, temperature, and sex hormonal levels, the activity of black cohosh extracts at the human μ opiate receptor (hMOR) expressed in Chinese hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2-propanol extracts of black cohosh effectively displaced the specific binding of [3H]DAMGO to hMOR. Further studies of the clinically used ethanol extract indicated that black cohosh acted as a mixed competitive ligand, displacing 77 ± 4% [3H]DAMGO to hMOR (Ki = 62.9 μg/mL). Using the [35S]GTPγS assay, the action of black cohosh was found to be consistent with an agonist, with an EC50 of 68.8 ± 7.7 μg/mL. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms.

CONSTITUENTS
triterpene glycosides (e.g. cycloartanes) reduce cytokine-induced bone loss (osteoporosis)
by blocking osteoclastogenesis
tannins inhibit iron absorption
extracts standardized by content of a saponin named 26-deoxyactein (aka 27-deoxyactein)

A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative, cimicifugic acid G (2), together with 15 known polyphenols, protocatechuic acid, protocatechualdehyde, p-coumaric acid, caffeic acid, methyl caffeate, ferulic acid, ferulate-1-methyl ester, isoferulic acid, 1-isoferuloyl-β-d-glucopyranoside, fukinolic acid, and cimicifugic acids A, B, and D−F, were isolated from an extract of the rhizomes and roots of black cohosh (Actaea racemosa). The structures of the new compounds were determined on the basis of NMR spectroscopic analysis. Compounds 1 and 2 displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay with IC50 values of 26 and 37 μM, respectively. Other antioxidants identified from A. racemosa include cimicifugic acid A (3), cimicifugic acid B (4), and fukinolic acid (5). Compounds 1 and 2 also exhibited a small stimulating effect on the growth of MCF-7 breast cancer cell proliferation 1.24-fold (14 μM) and 1.14-fold (10 μM), respectively, compared to untreated cells.

A compound recently identified in black cohosh (fukinolic acid) was shown to have estrogenic activity in vitro [10]. Other active compounds appear to include triterpene glycosides (including actein and cimicifugoside), resins (including cimicifugin), and caffeic and isoferulic acids [19].


SEs
No mutagenic or toxic effects have noted from the ingestion of Cimicifuga
not dangerous short term http://www.informapharmascience.com/doi/abs/10.1517/14740338.3.6.615
not recommended during menses, may increase/prolong bleeding??
not recommended for long term use: 6 mo limit???
some studies have suggested that long-term use may promote metastasis of cancer tissue in mice
(did not increase incidence of primary breast cancer, but increased mets of pre-existing breast cancer to the lungs)(study quoted above disputes this)
liver damage in some pts???
??? other: dizziness, headaches, seizures; diarrhea; nausea and vomiting; sweating; constipation; low blood pressure and slow heartbeats; and weight problems

DOSAGES
not for longterm use, up to 60 months OK?
Remifemin = commercial standardized black cohosh preparation w/ 20 mg of root per tablet
commercial preparations usu contain 1 mg total triterpene saponins in each 20-mg dose

ON ACTIONS by Stansbury
One recent study evaluated the effects of Cimicifuga versus a placebo in 110 menopausal women. The women were given 8 mg of Cimicifuga or the placebo per day for 8 weeks, and then blood levels of LH (Luteinizing hormone) and FSH (Follicle stimulating hormone) were checked. The LH levels were lower in the women who were given the Cimicifuga, than those receiving placebo. The FSH levels were similar in both groups. This indicates that Cimicfuga may have an estrogenic effect. The brain secretes LH to stimulate the ovaries to produce estrogen. As the ovaries cease ovulating and release less estrogen, the brain starts secreting more LH in attempts to raise the estrogen level. LH levels are higher in postmenopausal women than in menstruating women. If Cimicifuga reduces the levels of LH, it suggests it has an estrogen promoting effect. Early studies noted Cimicifuga to suppress LH but later studies could not confirm this action. (other sources says that 3 out of 4 studies have not supported any action on FSH and LH levels)

Animal studies have shown Cimicifuga constituents to bind estrogen receptors in the uterus and pituitary , but do not appear to affect estrogen via LH. , Thus the mechanism of any estrogenic effect on the tissues by Cimicifuga is yet unknown, but may involve the isoflavones.

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