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Tytuł pozycji:

Diosmin restores the skin barrier by targeting the aryl hydrocarbon receptor in atopic dermatitis.

Tytuł:
Diosmin restores the skin barrier by targeting the aryl hydrocarbon receptor in atopic dermatitis.
Autorzy:
Lee J; Division of Functional Food Research, Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, South Korea.
Song KM; Division of Strategic Food Technology Research, Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, South Korea.
Jung CH; Division of Functional Food Research, Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, South Korea; Department of Food Biotechnology, Korea University of Science and Technology, Daejeon 34113, South Korea. Electronic address: .
Źródło:
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2021 Jan; Vol. 81, pp. 153418. Date of Electronic Publication: 2020 Nov 25.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: Stuttgart : Urban & Fischer Verlag
Original Publication: Stuttgart ; New York : G. Fischer, c1994-
MeSH Terms:
Basic Helix-Loop-Helix Transcription Factors/*metabolism
Dermatitis, Atopic/*drug therapy
Dermatologic Agents/*pharmacology
Diosmin/*pharmacology
Receptors, Aryl Hydrocarbon/*metabolism
Skin/*drug effects
Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cell Line ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; DNA-Binding Proteins/metabolism ; Dermatitis, Atopic/pathology ; Drug Evaluation, Preclinical/methods ; Filaggrin Proteins ; Gene Expression Regulation/drug effects ; Humans ; Intermediate Filament Proteins/genetics ; Intermediate Filament Proteins/metabolism ; Keratinocytes/drug effects ; Keratinocytes/metabolism ; Keratinocytes/pathology ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Phytochemicals/pharmacology ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/genetics ; Skin/metabolism ; Skin/pathology ; Th2 Cells/metabolism ; Transcription Factors/metabolism ; Up-Regulation/drug effects
Contributed Indexing:
Keywords: Aryl hydrocarbon receptor; Atopic dermatitis; Diosmin; Filaggrin; Normal human epidermal keratinocytes
Substance Nomenclature:
0 (AHR protein, human)
0 (Basic Helix-Loop-Helix Transcription Factors)
0 (DNA-Binding Proteins)
0 (Dermatologic Agents)
0 (FLG protein, human)
0 (Filaggrin Proteins)
0 (Intermediate Filament Proteins)
0 (Membrane Proteins)
0 (OVOL1 protein, human)
0 (Phytochemicals)
0 (Receptors, Aryl Hydrocarbon)
0 (Transcription Factors)
0 (loricrin)
7QM776WJ5N (Diosmin)
EC 1.14.14.1 (CYP1A1 protein, human)
EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
Entry Date(s):
Date Created: 20201210 Date Completed: 20210224 Latest Revision: 20211204
Update Code:
20240104
DOI:
10.1016/j.phymed.2020.153418
PMID:
33302042
Czasopismo naukowe
Background: Atopic dermatitis (AD) is an inflammatory chronic skin disease that is characterized by the dysfunction or lack of skin barrier proteins. Recent studies have proposed that the pharmacological upregulation of skin barrier proteins is an effective treatment for AD. Aryl hydrocarbon receptor (AhR) is a transcription factor that positively regulates the expression of skin barrier proteins upon its activation.
Purpose: This study aimed to identify AhR agonists from phytochemicals and investigate its effect on skin barrier restoration as well as its mechanisms of action in AD.
Study Design: A publicly available assay database and HaCaT cells stably transduced with a luciferase gene driven by an AhR-target gene promoter (CYP1A1) were used to screen for the activity of AhR agonists from phytochemicals. Normal human epidermal keratinocytes (NHEKs) and a human skin equivalent (HSE) model were used to investigate the effect of AhR agonists on skin restoration and its underlying mechanisms.
Methods: A Gaussia luciferase assaywas performed to screen for AhR agonist activity. Western blotting, qRT-PCR analysis, immunofluorescence, drug affinity responsive target stability assay, and siRNA-mediated AhR knockdown were performed in NHEKs. Hematoxylin and eosin staining was performed to measure epidermal thickness in the HSE model.
Results: Diosmin, a potential AhR agonist derived from natural products, upregulated the expression of skin barrier proteins (filaggrin and loricrin) and their upstream regulator (OVOL1) in NHEKs. Diosmin treatment also increased epidermal thickness in the HSE model. In addition, incubating NHEKs with diosmin restored the expression of skin barrier proteins and mRNAs that were suppressed by Th2 cytokines and inhibited STAT3 phosphorylation that was induced by Th2 cytokines. Diosmin also upregulated the expression of NQO1, a negative regulator of STAT3. Immunofluorescence results showed that diosmin stimulated AhR nuclear translocation, and the drug affinity responsive target stability assay revealed that this phytochemical directly bound to AhR. Furthermore, AhR knockdown abolished diosmin-induced filaggrin and loricrin expression.
Conclusion: These results suggest that diosmin is a potential treatment for AD that targets AhR.
(Copyright © 2020. Published by Elsevier GmbH.)

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