# In Silico Target Discovery of Kaempferol: Therapeutic Effect of Kaempferol on Atopic Dermatitis through Regulation of Aryl Hydrocarbon Receptor

## TL;DR

This study explores how kaempferol, a plant compound, may treat atopic dermatitis by regulating the aryl hydrocarbon receptor.

## Contribution

The study identifies kaempferol as a novel regulator of the aryl hydrocarbon receptor for atopic dermatitis treatment.

## Key findings

- Kaempferol regulates epidermal differentiation proteins through the AhR pathway in HaCaT cells.
- Kaempferol shows therapeutic effects in AD-induced mouse models and human skin models.
- Kaempferol enhances epidermal terminal differentiation via AhR signaling in keratinocytes.

## Abstract

The aryl hydrocarbon receptor (AhR) is known to bind several exogenous ligands such as natural plant flavonoids, synthetic polycyclic aromatic hydrocarbons, and dioxin-like compounds, but its association with kaempferol (KF) is unknown. Therefore, in this study, AhR was explored as an atopic dermatitis (AD)-regulating target of KF for AD regulation using in silico prediction, and pharmacological prediction and various AD-induced models confirmed that KF exhibited pharmacological activity through AhR regulation. Also, the results of the study showed that KF regulated epidermal differentiation terminal proteins through the AhR pathway in HaCaT cells stimulated with TNF-α/IFN-γ, and the therapeutic effect of KF was also proven in an AD-induced mouse model and a reconstructed human skin model. In this study, AhR was explored as a KF–AD combined treatment target through in silico prediction analysis, and KF was proven to have an AD treatment effect through AhR regulation in vitro and vivo and in the reconstructed human skin model. In particular, KF can be used as a potent inducer of AhR signaling because it protects against AD by enhancing epidermal terminal differentiation through the AhR-mediated pathway in keratinocytes.