Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin

PLoS One. 2014 Dec 15;9(12):e115359. doi: 10.1371/journal.pone.0115359. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Biological Availability
  • Cells, Cultured
  • Female
  • Glucuronides / metabolism*
  • Humans
  • Inflammation / drug therapy
  • Male
  • Mice
  • Resveratrol
  • Skin / metabolism
  • Skin Absorption*
  • Stilbenes / administration & dosage
  • Stilbenes / metabolism
  • Stilbenes / pharmacokinetics*
  • Stilbenes / therapeutic use

Substances

  • Glucuronides
  • Stilbenes
  • dihydroresveratrol
  • Resveratrol

Grants and funding

Itsuo Murakami was supported by a postdoctoral fellowship from Okinawa Intellectual Cluster Program. Romanas Chaleckis was supported by Japanese government (Monbukagakusho: MEXT) scholarship. This work was supported in part by grants from the Okinawa Intellectual Cluster Program, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and from Japan Science and Technology Agency (to H.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.