Genistein‐ and daidzein 7‐O‐β‐D‐glucuronic acid retain the ability to inhibit copper‐mediated lipid oxidation of low density lipoprotein

Abstract

Two isoflavones in vivo metabolites, genistein-7-O-beta-D-glucuronic acid (G7G) and daidzein-7-O-beta-D-glucuronic acid (D7G) were synthesised chemically. The ability of these metabolites to scavenge an organic radical was measured by the trolox equivalent antioxidant capacity (TEAC) assay, while their reducing ability was measured by the ferric reducing antioxidant power (FRAP) assay. The TEAC and FRAP values of G7G were 45 and 51% of that of genistein, while those of D7G were 52 and 77% of that of daidzein, respectively. A direct assessment of G7G and D7G antioxidant activity by their ability to delay copper(II)-mediated lipid oxidation of human LDL showed that these metabolites retained the ability to prevent oxidation in the lipid phase, but activity was diminished compared to their corresponding aglycones. However, G7G and D7G also decreased the rate of lipid oxidation to 53 and 86% of control without isoflavones, respectively, indicating a continuous exchange of antioxidants between the aqueous environment and the LDL lipid phase during the whole oxidation period.

Biotransformed product, genistein 7-O-phosphate, enhances the oral bioavailability of genistein

“…Previous reports suggested that genistein was a substrate for several intestinal efflux transporters such as the ABCG2 gene product breast cancer resistance protein (BCRP) (Enokizono et al, 2007) and was reported to be mainly metabolized by UDP glucuronosyltransferase (UGT) to genistein glucuronide (Kgomotso et al, 2008), which can restrict systemic exposure after oral administration. G7P could be a promising alternative to genistein in increasing the contact of genistein to the epithelial membrane by improving aqueous solubility and likely by contributing to saturate intestinal efflux and metabolism, thus enhancing transepithelial flux and increasing systemic exposure (Heimbach, Fleisher, & Kaddoumi, 2007).…”

“…Structure-activity relationship studies revealed that genistein had a 48-fold higher affinity for ER β than isoflavone daidzein because of an additional hydroxyl biophore and a 9.1-Å intramolecular distance between biophores (Larrosa, González-Sarrías, García-Conesa, Tomás-Barberán, & Espín, 2006;Morito et al, 2001). Hence, genistein is the most potent antioxidant and estrogenically active molecule among phytoestrogenic isoflavones (Kgomotso, Chiu, & Ng, 2008).…”

“…These disadvantages lead to the depletion of genistein absorption from dietary intake and contribute to its poor oral bioavailability. In addition, genistein's significant first-pass metabolism (glucuronidation and sulfation) affects its bioavailability (Kgomotso et al, 2008;Sepehr, Cooke, Robertson, & Gilani, 2007), which might limit its pharmaceutical and nutraceutical effects.…”

Breast Cancer Resistance Protein (ABCG2) Determines Distribution of Genistein Phase II Metabolites: Reevaluation of the Roles of ABCG2 in the Disposition of Genistein

“…On the other hand, although generally less active than the aglycone, genistein glucuronides retain the ability to prevent lipid oxidation and possess modest activity to enhance human natural killer cells at nutritionally relevant concentrations (Zhang et al, 1999b;Kgomotso et al, 2008). In addition, genistein conjugates including sulfates can serve as the reservoir of parent compound in vivo by being substrates for futile (both enteric and enterohepatic) recycling and for hydrolysis in tissues (Sfakianos et al, 1997;Chen et al, 2003).…”

Mechanisms of anti-atherosclerotic functions of soy-based diets

“…However, Kapiotis et al [87] have reported that only genistein (2.5 μM), not daidzein, inhibits in vitro LDL oxidation. Interestingly, equol and 8-hydroxydaidzein, principal metabolites of daidzein, are potent inhibitors of oxLDL generation than the parent daidzein [89,90]. These in vitro studies have also been supported by in vivo animal studies.…”