Downregulation of aryl hydrocarbon receptor-mediated gene expression by Fraglide-1, a PPARγ agonist isolated from aromatic vinegar

Abstract

Fraglide-1 (FG1), a lactone isolated from the traditional Chinese Zhenjiang aromatic vinegar Kozu, has previously demonstrated antiobesity, antifungal, and antioxidant properties. Given the role of the aryl hydrocarbon receptor (AhR) in the pathogenesis of atopic dermatitis and its association with the neurotrophic factor artemin, we investigated the potential of FG1 as an AhR ligand in this study. Docking simulations revealed promising interactions between FG1 and AhR. Subsequent cell-based reporter assays using a human skin keratinocyte cell line showed that FG1 effectively suppressed the AhR-mediated induction of genes with a xenobiotic response element (AhR/XRE), which in turn downregulated the expression of artemin, a biomarker of atopic dermatitis. FG1 demonstrated not only comparable efficacy but also superior safety compared with the known AhR inhibitor StemRegenin 1. These results not only underscore the therapeutic promise of FG1 in atopic dermatitis but also reinforce its previously known bioactivities, such as antiobesity, antifungal, and antioxidant effects, which indicate that it is a versatile compound with multiple health benefits.