title: Prenylation enhances quercetin uptake and reduces efflux in Caco-2 cells and enhances tissue accumulation in mice fed long-term.
abstract: Prenyl flavonoids are widely distributed in plant foods and have attracted appreciable attention in relation to their potential benefits for human health. Prenylation may enhance the biological functions of flavonoids by introducing hydrophobic properties in their basic structures. Previously, we found that 8-prenyl naringenin exerted a greater preventive effect on muscle atrophy than nonprenylated naringenin in a mouse model. Here, we aimed to estimate the effect of prenylation on the bioavailability of dietary quercetin (Q). The cellular uptake of 8-prenyl quercetin (PQ) and Q in Caco-2 cells and C2C12 myotube cells was examined. Prenylation significantly enhanced the cellular uptake by increasing the lipophilicity in both cell types. In Caco-2 cells, efflux of PQ to the basolateral side was <15% of that of Q, suggesting that prenylation attenuates transport from the intestine to the circulation. After intragastric administration of PQ or Q to mice or rats, the area under the concentration-time curve for PQ in plasma and lymph was 52.5% and 37.5% lower than that of Q, respectively. PQ and its O-methylated form (MePQ) accumulated at much higher amounts than Q and O-methylated Q in the liver (Q: 3400%; MePQ: 7570%) and kidney (Q: 385%; MePQ: 736%) of mice after 18 d of feeding. These data suggest that prenylation enhances the accumulation of Q in tissues during long-term feeding, even though prenylation per se lowers its intestinal absorption from the diet.
authors.affiliation: Department of Food Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Mukai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujikura
authors.forename: Kaeko
authors.initials: K
authors.lastname: Murota
authors.forename: Mariko
authors.initials: M
authors.lastname: Uehara
authors.forename: Shoko
authors.initials: S
authors.lastname: Minekawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Matsui
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawamura
authors.forename: Hisao
authors.initials: H
authors.lastname: Nemoto
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D054876:Prenylation; D011794:Quercetin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011794:Quercetin