| endocrine activity
Studies of the Chinese traditional medicine, shengma, showed that injections of the extract increased uterine weight and "established the estrous cycles" of immature adolescent and climacteric female rats. In adolescent rats, ovarian weight and the number of corpora lutea also increased (Chang & But 1986). ÒShengmaÓ refers to several species of Cimicifuga, viz., C. heracleifolia Kom., C. dahurica (Turcz.) Maxim., or C. foetida L.; it is not clear from the original reference which of these species was used in these experments, or whether a mixture was used.
Constituents of Cimicifuga racemosa rhizome can bind to estrogen receptors in rat uteri and pituitary glands, but some controversy exists as to what estrogenic effects result from occupying these sites. Duker et al. (1991) characterized pharmacological responses to various chromatographically separated fractions of C. racemosa lipophilic extract in ovarectomized rats. Fractionation studies using ovariectomized rats resulted in the isolation of three endocrinologically active fractions: fraction I inhibited 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, and did not suppress 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 explain that the lack of an effect on 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 not confirmed, and is speculation. 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). While this and other studies (Jarry & Harnischfeger 1985) on ovarectomized rats, as well as menopausal women, demonstrated reduced lutenizing hormone (LH) levels, a new study (Einer-Jensen 1996) indicates a lack of estrogenic effects in rats and mice. A recent study also states that no significant decrease in LH (or other hormonal changes) or other measures of estrogenic activity (e.g. increased vaginal epithelium thickness) are attributable to the Cimicifuga racemosa preparation, Remifemin (Liske 1998), at least when the new lower dose (now recommended by the manufacturers of Remifemin; cf. Schaper & BrŸmmer 1997) is used. Numerous studies have consistently shown no effect on follicle stimulating hormone (FSH).
Isopropanolic aqueous extracts of Cimicifuga racemosa inhibit in vitro proliferation of estrogen-dependent breast cancer cell lines in a dose-dependent manner. This is interpreted as an estrogen-receptor blockade by the extract (Nesselhut et al. 1993). In a follow-up study, Cimicifuga prevented the stimulation of estrogen-dependent cancer cells when estrogen was added in vitro. Tamoxifen and Cimicifuga 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, submitted).
Two recent studies of other Cimicifuga species, C. foetida and C. heracleifolia, demonstrated inhibition of parathyroid hormone-induced bone resorption in tissue culture (Li et al. 1996) and in ovarectomized rats (Li et al. 1995). This anti-osteoporotic effect has not, as yet, been discussed in the literature, in terms of Cimicifuga racemosa's estrogen receptor-binding activity, although mention was made of C. racemosa's positive influence on osteoporotic states by Murray (1997).
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