23 research outputs found
Silymarin is a selective estrogen receptor β (ERβ) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats
Silymarin is a widely used standardized mixture of flavonolignans and its major component Silybinin binds to cytosolic estrogen receptors. Here, we demonstrate that this binding is exclusive to the estrogen receptor beta (ERbeta). Treatment of ovariectomized (ovx) rats with silymarin or estradiol (E-2) may allow differentiation of biological effects mediated by the ERalpha or ERbeta. E-2 inhibited serum LH, cholesterol, LDL and HDL concentrations in the blood and increased gene expression of IGF1, HbEGF and C3 in the uterus, while silymarin was totally ineffective or antagonistic in altering these parameters. Both, E-2 and silymarin inhibited expression of uterine ERbeta gene. Hence, in the pituitary, liver (where the lipoproteins are synthesized) and uterus E-2 acts primarily via the ERalpha. Exclusive estrogenic effects of silymarin were observed in the metaphysis of the femur (W), on osteoblast parameters (gene expression of IGF1, TGFbeta1, osteoprotegerin, collagen-1alpha1, osteocalcin (OC)) and on the osteoclast activity marker tartrate resistant acid phosphatase (TRAP) gene expression of adult ovx rats. Our RT-PCR method detects ERbeta gene expression in all organs including developing bones but not in the ME of adult ovx rats. We conclude therefore, that the effects of silymarin in this part of the bone cannot be exerted via the ERalpha because it does not bind to this receptor subtype. Despite the failure to detect ERbeta mRNA in the MF of our animals the possibility exists that ERbeta protein is present and may mediate the effects of silymarin. Another possibility may be that the effect of silymarin and therefore possibly also of E-2 in the MF may be mediated via other possibly not yet identified receptors or via an ERbeta splice variant which is not detected by our PCR-method. (C) 2003 Elsevier Ltd. All rights reserved
Black cohosh (Cimicifuga racemosa) is a non-estrogenic alternative to hormone replacement therapy
Hormone replacement therapy is still a popular and most effective treatment for vasomotor symptoms and bone loss prevention in the postmenopause but it is not without risks. This has driven many climacteric women to seek for alternatives, chiefly natural products. Phytoestrogens containing soy or red clover preparations, however, when taken at the recommended daily doses, proved to be ineffective to ameliorate climacteric complaints and to prevent osteoporosis. Cimicifuga racemosa (CR) preparations, on the other hand, have been shown to ease climacteric distress. There is a widespread, but false, belief that the efficacy of CR preparations is linked to the presence of phytoestrogens in the plant. This review aims at summarizing the available in vitro and in vivo evidence showing that compounds in CR extracts do not bind to oestrogen receptors and thus do not exert any estrogenic effects in the uterus and mammary gland, as shown in vivo in experiments on ovariectomized rats and clinically in postmenopausal women. Studies in ovariectomized rats and in women suffering from climacteric complaints have indicated that substances with neurotransmitter-like activities affect beneficially postmenopausal symptoms such as hot flushes. Some of these compounds, such as actein-like triterpenes with GABA-ergic activity and a serotonin analogue, are present and have been identified in the CR extracts. We conclude that these activities explain most likely the beneficial effects of CR extracts on climacteric complaints