Evaluation of the Estrogenic Activity of Green and Fermented Aspalathus linearis (Rooibos) Extracts

Abstract The presence of plant polyphenols with pharmacophoric features similar to estrogens in an Aspalathus linearis (rooibos) extract warranted the in vitro evaluation of the estrogenic activity of green and fermented rooibos extracts (n = 18). Whole-cell receptor binding assays demonstrated that compounds found within the rooibos extracts interact with both estrogen receptor (ER) subtypes, as they displaced radiolabeled E2. Although the extracts were much less potent than E2 in inducing agonism in promoter-reporter luciferase assays, most extracts displayed ERβ selectivity with higher efficacy via ERβ than via ERα. In contrast, extract potencies were generally comparable to ICI-182,780, an ER antagonist, in antagonizing E2, while their efficacies showed no ER-subtype selectivity. The preference of selected water extracts (WEs) to signal via ERβ was apparent in their inability to induce progesterone receptor (PGR) mRNA expression, an ERα-activated gene. Furthermore, the lack of PGR stimulation was consistent with Western blot assay results, where most WEs downregulated PR-B protein expression after shorter treatment times (2 or 4 h) and inhibited E2-induced PR-B protein expression after 24 or 48 h. To our knowledge, this study is the first to report that rooibos possesses antiestrogenic activity. This warrants further research for identifying the active compound(s) underlying the antiestrogenic effect, and for supporting the potential of rooibos as a therapeutic agent in diseases regulated by E2, such as ER-positive breast cancer.