Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption

Shih Yi Chuang, Yin Ku Lin, Chwan Fwu Lin, Pei Wen Wang, En Li Chen, Jia You Fang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

64 Scopus citations

Abstract

Flavonoids are bioactive phytochemicals that exhibit protective potential against cutaneous inflammation and photoaging. We selected eight flavonoid aglycones or glycosides to elucidate the chemistry behind their skin absorption capability through experimental and computational approaches. The skin delivery was conducted using nude mouse and pig skins mounted on an in vitro Franz cell assembly. The anti-inflammatory activity was examined using the O2•– and elastase inhibition in activated human neutrophils. In the equivalent dose (6 mM) application on nude mouse skin, the skin deposition of naringenin and kaempferol was 0.37 and 0.11 nM/mg, respectively, which was higher than that of the other flavonoids. Both penetrants were beneficial for targeted cutaneous therapy due to their minimal diffusion across the skin. The absorption was generally greater for topically applied aglycones than glycosides. Although naringenin could be classified as a hydrophilic flavonoid, the flexibility of the chiral center in the C ring of this flavanone could lead to better skin transport than the flavonols and flavones with a planar structure. An optimized hydrophilic and lipophilic balance of the flavonoid structure was important for governing the cutaneous delivery. The hydrogen bond acceptor and stratum corneum lipid docking estimated by molecular modeling showed some relationships with the skin deposition. The interaction with cholesteryl sulfate could be a factor for predicting the cutaneous absorption of aglycone flavonoids (correlation coefficient = 0.97). Baicalin (3 μM) showed the highest activity against oxidative burst with an O2•– inhibition percentage of 77%. Although naringenin displayed an inhibition efficiency of only 20%, this compound still demonstrated an impressive therapeutic index because of the high absorption. Our data are advantageous to providing the information on the structure–permeation relationship for topically applied flavonoids.

Original languageEnglish
Article number1304
JournalNutrients
Volume9
Issue number12
DOIs
StatePublished - 12 2017

Bibliographical note

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Anti-inflammation
  • Cutaneous absorption
  • Flavonoid
  • Molecular modeling
  • Structure–permeation relationship

Fingerprint

Dive into the research topics of 'Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption'. Together they form a unique fingerprint.

Cite this