The non-estrogenic alternative for the treatment of climacteric complaints: Black cohosh (Cimicifuga or Actaea racemosa).

In postmenopausal women estrogens in combination with progestins have beneficial effects on climacteric complaints and on osteoporosis but this hormone replacement therapy (HRT) bears the risk of increased mammary carcinomas and cardiovascular diseases. Phytoestrogens at low doses have little or no effects on climacteric complaints, at high doses they mimic the effects of estrogens. Therefore other plant derived substances are currently intensively investigated. Extracts of the rhizome of black cohosh (Cimicifuga racemosa=CR) did not bind to estrogen receptors and were shown to be devoid of estrogenic effects on mammary cancer cells in vitro and on mammary gland and uterine histology in ovariectomized rats. In addition in this rat model the special extract CR BNO 1055 inhibited the occurrence of hot flushes and development of osteoporosis. In postmenopausal women CR BNO 1055 reduced major climacteric complaints as effectively as conjugated estrogens and significantly more than placebo. Similar data were published for other European CR preparations whereas 2 US American preparations were ineffective. This was most likely due to the too high doses or due to the adulteration with Asian Cimicifuga preparations. In all European studies neither effects in the uterus nor in mammary glands were observed. The effective compounds in CR are most likely neurotransmitter-mimetic in nature: dopaminergic, noradrenergic, serotoninergic and GABAergic effects were demonstrated and some have been structurally identified. We conclude that CR extracts at low doses are effective to ameliorate climacteric complaints but are devoid of adverse estrogenic effects. These finding strengthens the role of CR extracts as substitutes for HRT. This article is part of a special issue entitled: Special Issue on Phytoestrogens.

Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055.

This study aimed to investigate the mechanisms underlying the anti-proliferative effects of the ethanolic Cimicifuga racemosa extract BNO-1055 on prostate cells and evaluate its therapeutic potential. BNO-1055 dose-dependently attenuated cellular uptake and incorporation of thymidine and BrdU and significantly inhibited cell growth after long-time exposure. Similar results were obtained using saponin-enriched sub-fractions of BNO-1055. These inhibitory effects of BNO-1055 could be mimicked using pharmacological inhibitors and isoform-specific siRNAs targeting the equilibrative nucleoside transporters ENT1 and ENT2. Moreover, BNO-1055 attenuated the uptake of clinically relevant nucleoside analogs, e.g. the anti-cancer drugs gemcitabine and fludarabine. Consistent with inhibition of the salvage nucleoside uptake pathway BNO-1055 potentiated the cytotoxicity of the de novo nucleotide synthesis inhibitor 5-FU without significantly altering its uptake. Collectively, these data show for the first time that the anti-proliferative effects of BNO-1055 result from hindered nucleoside uptake due to impaired ENT activity and demonstrate the potential therapeutic use of BNO-1055 for modulation of nucleoside transport.