Screening for in vivo (anti)estrogenic activity of ephedrine and p-synephrine and their natural sources Ephedra sinica Stapf. (Ephedraceae) and Citrus aurantium L. (Rutaceae) in rats.

Formulations containing Ephedra sinica Stapf. (Ephedraceae) and Citrus aurantium L. (Rutaceae) are consumed worldwide for body weight control. Considering the related adverse effects and the risk potential, the aim of this study is to evaluate the effects of the thermogenic compounds ephedrine, p-sinephrine, E. sinica and C. aurantium in the female reproductive system through the uterotrophic assay in immature female rats. The animals (n = 6-7) received E. sinica 85.5 and 855.0 mg/kg/day, C. aurantium 25.0 and 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day for three consecutive days by oral gavage. For detection of antiestrogenicity, tamoxifen 20.0 mg/kg/day, E. sinica 855.0 mg/kg/day, C. aurantium 50.0 mg/kg/day, ephedrine 5.0 mg/kg/day and p-synephrine 50.0 mg/kg/day were administered to estrogen-treated females. Macroscopical alterations were evaluated in liver, kidneys, adrenals and uterus. All analyzed substances showed an antiestrogenic potential, but only ephedrine at 0.5 mg/kg/day presented a significative antiestrogenic effect (P < 0.01). Adrenals relative mass were reduced (P < 0.01) in all tested compounds when compared to the control, which seems to be related to the alfa-1-adrenoceptor agonist activity, which promote a vasoconstriction and reduction of the liquid in the organ. The endocrine system is highly complex and there are a number of ways in which a chemical may interfere with it, other in vivo and in vitro assays are being necessary to support this mechanism of action.