Treatment with Qing'E, A Kidney-Invigorating Chinese Herbal Formula, Antagonizes the Estrogen Decline in Ovariectomized Mice

Abstract

A Chinese herbal preparation, Qing'E formula (QEF), has been used clinically for treating osteoporosis in postmenopausal women by virtue of its kidney-invigorating function; however, no evidence base links QEF to estrogen replacement therapy. In this study, we undertake a characterization of estrogenic activity of QEF using an in vivo model of ovariectomized (OVX) mice together with in vitro studies with the MCF-7 cells for further molecular characterization. OVX mice were treated intragastrically with QEF at doses of 0.85, 1.7, and 3.4 g/kg per day for 4 weeks. QEF treatments restored the estrus cycle and demonstrated significant estrogenic activity, as indicated by reversal of uterine atrophy (six-fold increase in uterine weight), reduction in rectal temperature, and increased expression (1.6-fold) of estrogen receptors (ERs) in the uterus. Notably, the largest changes in these three parameters were found at the lowest dose. At the highest dose of QEF, significant changes were found in adrenal gland weight (30% increase), serum estradiol (E(2)) (60% increase), and luteinizing hormone (LH) (17% decrease) compared with untreated OVX controls. The data suggest estrogenic responses induced by QEF show tissue variation that reflects different affinities of ERs for QEF components. QEF could significantly induce luciferase expression (2.7-fold compared with control) from an estrogen response element luciferase reporter and induced expression of ERalpha and ERbeta (1.2-fold and 1.7-fold respectively) in MCF-7 cells. Both activities were inhibited 80-90% by the estrogen antagonist ICI 182,780. This study demonstrates that QEF activity is mediated through estrogenic components and provides an evidence base for QEF treatment of postmenopausal symptoms.