Distribution of RESV and its metabolite peaks in mouse tissues after oral and skin administration

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.

RESV (1 mg in 200 µl saline) was orally administered to hairless mice or 1 mg RESV dissolved in ethanol was applied on the dorsal skin of hairless mice. After 4 h mice were sacrificed, metabolites were extracted from the tissues and analyzed by the LC-MS. Peak areas of metabolites were normalized by the peak areas of spiked internal standards (10 nmol 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and piperazine-N,N’-bis(2-ethanesulfonic acid) (PIPES).

INSTRUMENT(S): LTQ Orbitrap Classic (Thermo Scientific)

SUBMITTER: Romanas Chaleckis 

PROVIDER: MTBLS125 | MetaboLights | 2014-12-15

REPOSITORIES: MetaboLights