Deconjugation of soy isoflavone glucuronides needed for estrogenic activity

Abstract

Soy isoflavones (SIF) are present in the systemic circulation as conjugated forms of which the estrogenic potency is not yet clear. The present study provides evidence that the major SIF glucuronide metabolites in blood, genistein-7-O-glucuronide (GG) and daidzein-7-O-glucuronide (DG), only become estrogenic after deconjugation. The estrogenic potencies of genistein (Ge), daidzein (Da), GG and DG were determined using stably transfected U2OS-ERα, U2OS-ERβ reporter gene cells and proliferation was tested in T47D-ERβ cells mimicking the ERα/ERβ ratio of healthy breast cells and inT47D breast cancer cells. In all assays applied, the estrogenic potency of the aglycones was significantly higher than that of their corresponding glucuronides. UPLC analysis revealed that in U2OS and T47D cells, 0.2-1.6% of the glucuronides were deconjugated to their corresponding aglycones. The resulting aglycone concentrations can account for the estrogenicity observed upon glucuronide exposure. Interestingly, under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating these glucuronides than human breast tissue S9 fraction. Our study confirms that SIF glucuronides are not estrogenic as such, and that the small % of deconjugation in the cell is enough to explain the slight bioactivity observed for the SIF-glucuronides. Species differences in deconjugation capacity should be taken into account when basing risk-benefit assessment of these SIF for the human population on animal data.

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

“…In our study, the observed differences could be explained by the higher proportion of free isoflavones (aglycones) in rodents than in humans (Setchell et al, 2011) as it is hypothesized that aglycone forms are more bioactive than conjugated forms (M. A. Islam et al, 2015).…”

Red Maca (Lepidium meyenii) did not affect cell viability despite increased androgen receptor and prostate-specific antigen gene expression in the human prostate cancer cell line LNCaP

“…As red Maca aqueous extract also contains other organic compounds such as polyphenols, tanins, saponins, alkaloids, steroids or glycosides with oestrogenic and androgenic activity (Dini, Tenore, & Dini, 2002; Piacente, Carbone, Plaza, Zampelli, & Pizza, F I G U R E 1 Red Maca aqueous extract did not affect viability of LNCaP cells. Another possibility is that glucosinolates could need to be metabolised for activating anticancer properties in the prostate cancer cells (Islam et al, 2015). At 24 or 48 hr after treatment, cultured cells were processed to measure their viability as described in the Material and Methods section.…”

In vitro‐in silico‐based analysis of the dose‐dependent in vivo oestrogenicity of the soy phytoestrogen genistein in humans

“…The genistein conjugates tested so far, including genistein‐7‐O‐glucuronide (G‐7G), genistein‐7‐O‐sulfate (G‐7S) and genistein‐4′‐O‐sulfate (G‐4′S), appeared inactive in assays for oestrogenicity, leading to the conclusion that the action of the soy phytoestrogen genistein will be mainly related to the plasma and tissue concentration of the free aglycone (Yuan et al, ; Islam et al, ).…”