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Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption

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...

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Autores principales: Chuang, Shih-Yi, Lin, Yin-Ku, Lin, Chwan-Fwu, Wang, Pei-Wen, Chen, En-Li, Fang, Jia-You
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748754/
https://www.ncbi.nlm.nih.gov/pubmed/29189718
http://dx.doi.org/10.3390/nu9121304
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author Chuang, Shih-Yi
Lin, Yin-Ku
Lin, Chwan-Fwu
Wang, Pei-Wen
Chen, En-Li
Fang, Jia-You
author_facet Chuang, Shih-Yi
Lin, Yin-Ku
Lin, Chwan-Fwu
Wang, Pei-Wen
Chen, En-Li
Fang, Jia-You
author_sort Chuang, Shih-Yi
collection PubMed
description 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 O(2)(•–) 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 O(2)(•–) 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.
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spelling pubmed-57487542018-01-07 Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption Chuang, Shih-Yi Lin, Yin-Ku Lin, Chwan-Fwu Wang, Pei-Wen Chen, En-Li Fang, Jia-You Nutrients Article 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 O(2)(•–) 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 O(2)(•–) 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. MDPI 2017-11-30 /pmc/articles/PMC5748754/ /pubmed/29189718 http://dx.doi.org/10.3390/nu9121304 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chuang, Shih-Yi
Lin, Yin-Ku
Lin, Chwan-Fwu
Wang, Pei-Wen
Chen, En-Li
Fang, Jia-You
Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title_full Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title_fullStr Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title_full_unstemmed Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title_short Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption
title_sort elucidating the skin delivery of aglycone and glycoside flavonoids: how the structures affect cutaneous absorption
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748754/
https://www.ncbi.nlm.nih.gov/pubmed/29189718
http://dx.doi.org/10.3390/nu9121304
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