Medicinal Botanicals: Modulation of Estrogen Action

Medicineal Botanicals:Modulation of Estrogen Action

Eagon, P.K., Hunter, D.S., Elm, M.S., Tress, N.B., Eagon, C.L. M.D. Anderson Cancer Center, Smithville, TX and University of Pittsburgh and VA Medical Center, Pittsburgh, PA

Medicinal Botanicals are of increasing interest to those seeking alternative health care and self-treatment for gynecological and menopausal symptoms. However, little is known about the safety, efficacy and hormonal properties of such products, an issue of concern to women with or at risk for breast and other hormone-responsive cancers.

Our previous studies have documented that several commonly used botanicals, including those in the current study, have potent estogenicity when tested in vivo in ovariectomized female rats. In this study, plant extracts were tested in an in vitro competitive estrogen receptor (ER) binding assay performed in parallel with diethylstilbestrol and genistein.

Extracts of several botanicals, including dang gui (dong quai), black cohosh, and hops, resulted in significant dose-dependent inhibition of radiolabeled estradiol (E2) binding to the ER, while milk thistle, licorice root, blue cohosh, and wild yam enhanced E2 binding to ER.

Wild yam and sqaw vine also enhanced binding of the radiolabeled synthetic progestin R5020 to cystolic progesterone receptor. Some extracts also were tested in a reporter gene assay for ER-mediated transactivation in transformed estrogen-responsive cells derived from an Eker rat uterine leiomyoma.

Milk thistle, licorice root, dang gui, hops and wild yam alone, like E2, were able to induce reporter gene expression in a dose-dependent manner. When tested additionally in the presence of a maximum stimulatory dose of E2, extracts that enhanced binding to the ER, i.e., milk thistle, licorice root, and blue cohosh, also enhanced reporter gene expression beyond that of E2 alone.

In contrast dang gui, which inhibited binding to the ER in vitro, also inhibited E2-induced reporter gene induction in the leiomyoma cells.

This work verifies that certain medicinal botanicals demonstrate significant estrogenic activities. In addition, it appears that at least some of these botanicals, in the presence of phsyiological levels of E2, may amplify or inhibit ER-mediated cellular events.

This work was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-97-1-7086.

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