title: Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.
abstract: Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.
authors.affiliation: Geriatric unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Murakami
authors.affiliation: Geriatric unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan; G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Onna-son, Okinawa, Japan.
authors.forename: Romanas
authors.initials: R
authors.lastname: Chaleckis
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Onna-son, Okinawa, Japan.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Pluskal
authors.affiliation: Geriatric unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ito
authors.affiliation: Geriatric unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Hori
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Onna-son, Okinawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ebe
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Onna-son, Okinawa, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
authors.affiliation: Geriatric unit, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondoh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D005260:Female; D020719:Glucuronides / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D000077185:Resveratrol; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D020719:Glucuronides; D013267:Stilbenes; C544754:dihydroresveratrol; D000077185:Resveratrol