Evaluation of the medicinal botanical Rhodiola rosea for estrogenicity

Abstract

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Our previous work has identified numerous plant extracts that interact with estrogen receptor (ER) and induce estrogenic responses in ovariectomized (OVX) female rats and in cell lines. While many such botanicals are traditionally used for gynecological complaints, others are used for different purposes and thus their estrogenicity was unexpected. Rhodiola rosea Crassulaceae (RR) root, also known as roseroot, Arctic root, or goldenroot, is a medicinal botanical with a long history of use as a strengthening tonic and an adaptogen. RR has been used to relieve perimenopausal symptoms such as fatigue, depression, and cognitive and memory problems. Recent studies have shown antimutagenic and anticarcinogenic effects in vitro and in vivo, and that RR increases effectiveness of cancer chemotherapeutic agents while protecting bone marrow stem cells and hepatocytes against chemotoxicity. Since patients who have or are at risk for hormone-responsive cancers might seek to avoid estrogenic agents, the aim of this study was to determine if a standard extract of RR (3% rosavins: 1% salidrosides) demonstrates estrogenic activity, using in vivo and in vitro measures. In an in vitro competitive ER binding assay, significant dose-dependent inhibition of radiolabeled estradiol (E₂) binding to ER was observed with RR. When fed to ovariectomized (OVX) female rats at a dose equivalent to 30% of the recommended human dose for 30 days, RR did not increase uterine weight, reduce serum LH levels, nor alter serum E₂ levels or hepatic estrogen 2-hydroxylase (E2OHase) activity. Further, in OVX rats treated with E₂, administration of RR resulted in enhanced (30%, p<0.05) hepatic E2OHase activity and a slight reduction (10-20%, NS) in serum E₂ levels; however, RR did not alter uterine weight nor LH levels in the E₂-treated rats beyond that observed with E₂ alone. In other studies, possible proliferative effects of RR were examined using MCF-7 breast cancer cells. At 24 hours after seeding, cells were counted (zero time) and parallel flasks were treated with E₂ (1nM), or RR at low (.065μg/ml) or high (.065mg/ml) doses, or a combination of RR and E₂; a non-treatment group was used as control. After 24, 48, and 72 hours of exposure, cells were counted and the medium and treatment renewed. Growth of cells treated with high dose RR, with or without E₂, was identical to that of E₂-treated or untreated control cells, respectively, while low dose RR exhibited a slight stimulation of growth. These studies demonstrate that RR interacts with the ER, suggesting estrogenic or antiestrogenic potential. However, treatment of OVX rats did not invoke estrogenic responses in uterus or pituitary. Further, when administered with estradiol, RR does not potentiate estrogen action in OVX rats, and appears to increase metabolism of E₂. This work suggests that RR, when taken orally, is unlikely to present an estrogenic risk to women who may seek to avoid such agents.