Resveratrol metabolism in HepG2 (human hepatocytes), HaCaT (human keratinocytes), and C2C12 (mouse myoblasts)

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.

Cells were treated with 0, 20 or 200 µM RESV for 4 h. After washing with PBS, cells were lysed, and metabolites were extracted and analyzed by LC-MS. Peak areas metabolites were normalized by peak areas of spiked internal standards (10 nmol 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and piperazine-N,N’-bis(2-ethanesulfonic acid) (PIPES). 3 samples for each condition (except for HaCaT 200 µM, 2 samples).

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

SUBMITTER: Romanas Chaleckis 

PROVIDER: MTBLS127 | MetaboLights | 2014-12-15

REPOSITORIES: MetaboLights