Atopic dermatitis (AD) leading to the dysfunction or lack of skin barrier proteins, is a well known inflammatory chronic skin disease. The pharmacological up regulation of skin barrier proteins is being reviewed as a promising treatment for AD nowadays. Aryl hydrocarbon receptor (AhR) is a transcription factor, which on activation emphatically regulates the expression of skin barrier proteins.

A study published by Lee J. et al aimed to identify AhR agonists from phytochemicals and investigate their effect on skin barrier restoration, along with their mechanisms of action in AD.

The study utilized a Gaussia luciferase assay performed to screen for AhR agonist activity. Normal human epidermal keratinocytes (NHEKs) underwent Western blotting, qRT-PCR analysis, immunofluorescence, drug affinity responsive target stability assay, and siRNA-mediated AhR knockdown for the sake of the study. Along with, to measure the epidermal thickness in the human skin equivalent (HSE) model, Hematoxylin and eosin staining was done.

The researchers found that 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. Treatment with Diosmin also improved epidermal thickness in the HSE model.

Also, Diosmin incubated NHEKs reestablished the expression of skin barrier proteins and mRNAs that were suppressed by Th2 cytokines and inhibited STAT3 phosphorylation that was induced by Th2 cytokines. Along with this, Diosmin was also seen upregulating the expression of NQO1 (a negative regulator of STAT3). Diosmin also showed stimulated AhR nuclear translocation in immunofluorescence

The drug affinity responsive target stability assay showed that diosmin directly bound to AhR. Also, AhR knockdown ended diosmin-induced filaggrin and loricrin expression.

Thus they concluded that diosmin is a potential treatment for AD which targets AhR.

Source:  Lee, J, Song, KM, Jung, CH. Diosmin restores the skin barrier by targeting the aryl hydrocarbon receptor in atopic dermatitis. Phytomedicine, 2021.  doi: 10.1016/j.phymed.2020.153418.