Akari ISHISAKA

Quercetin (QUE), a flavonoid widely found in vegetables and fruits, is primarily metabolized through phase II conjugation pathways and circulates as various conjugates. We previously showed that QUE and its metabolites are transferred to neonatal mice via breast milk. However, as the dams in that study ingested QUE during pregnancy, placental transfer may also had occurred. Thus, this study aimed to investigate the placental transfer of QUE and its metabolites by quantifying their concentrations before parturition. ICR mice were fed a standard AIN-93G diet and mated, with gestational day 0 defined as the day of mating. On gestational day 14, the diet was switched to 1 % (w/w) QUE-supplemented AIN-93G. On gestational day 17, blood, liver, and placenta samples were collected from pregnant dams and fetuses. QUE and its metabolites were quantified using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. QUE and its metabolites were detected in the placenta and maternal liver, as well as in the fetal liver. The proportions of heteroconjugates (e.g., quercetin glucuronide sulfate and isorhamnetin glucuronide sulfate) in the placenta (59 %) and fetal liver (43 %) were lower than in maternal plasma (94 %). In contrast, monoconjugates (e.g., quercetin glucuronide, quercetin sulfate) and particularly free QUE were relatively abundant in both placenta and fetal liver. These findings suggest that heteroconjugates from maternal blood may be deconjugated in the placenta. To our knowledge, this is the first study to comprehensively analyze the placental transfer of QUE and its metabolites to fetuses in pregnant mice.

ABSTRACT Flavonoids are present in plant foods such as vegetables and fruits and exhibit various physiological effects, including antioxidant and anti-inflammatory properties. Ingested flavonoids are absorbed from the intestinal tract and circulated in the blood. Some studies have indicated the presence of flavonoids in breast milk. However, information on their metabolites and concentrations in breast milk and the subsequent transfer to and physiological functions in infants is limited. Therefore, this review presents a compilation of recent findings on the transfer of flavonoids to infants via breast milk and their bioactivities.