Trans-resveratrol alleviates inflammation and improves skin barrier function via aryl hydrocarbon receptor pathway in...

The aryl hydrocarbon receptor (AHR) is a regulator of epidermal homeostasis and a promising target for cosmetic and dermatological ingredients aimed at improving skin barrier function and reducing inflammation. This study investigated the potential of the natural polyphenol trans-resveratrol (RSV), a compound of cosmetic interest, to modulate downstream AHR signalling and restore epidermal integrity in a model of skin compromised by a pro-inflammatory environment.

A reconstructed human epidermis (RhE) was exposed to a cytokine cocktail (IL-4, IL-13, TNF-α) to induce a phenotype mimicking some aspects of atopic eczema, namely inflammation, oxidative stress and barrier disruption, features also prevalent in sensitive and reactive skin conditions. The effects of RSV were evaluated by assessing inflammatory mediators, oxidative stress-related markers, aryl hydrocarbon receptor signalling and epidermal barrier-associated proteins using molecular, biochemical and histological analyses.

Cytokine exposure induced a pronounced inflammatory response, activation of aryl hydrocarbon receptor signalling, oxidative stress-related gene expression and dysregulation of barrier-related markers. Treatment with RSV attenuated the inflamed phenotype by reducing IL1A mRNA expression and IL-1α secretion, attenuating oxidative stress-associated AHR target gene responses through downregulation of CYP1A1 and CYP1B1, while maintaining AHR and HMOX1 expression and modulating barrier-associated gene expression, particularly by downregulating CASP14 and upregulating the tight junction protein occludin (OCLN).

These findings provide mechanistic evidence in a human epidermis model that RSV can counteract inflammation, mitigate oxidative stress and support epidermal barrier homeostasis, actions mediated, at least in part, through modulation of AHR downstream signalling. This supports the potential of resveratrol as a multifunctional active ingredient in cosmetic and dermatological formulations designed to strengthen the skin barrier and calm sensitive or compromised skin.