FICZ

In vitro studies in cells show that CYP1 inhibition in the presence of FICZ results in enhanced AHR activation, suggesting that FICZ accumulates in the cell when its metabolism is blocked.^[1] FICZ significantly upregulates the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but does not affect the gene expression of other barrier-related proteins.^[2]

HaCaTcells or NHEKs (1×10⁴ cells/well) are platedon an 8-well μ-slide for 48 h, and treated with or without FICZ for 3 or 1 h, respectively. Then, the cells are washed with phosphate-buffered saline (PBS), fixed with acetone for 10 min, and blocked with 5% (w/v) bovine serum albumin in PBS for 30 min. The cells are then incubated with primary rabbit anti-AHR antibody (1:100) overnight at 4 ℃. Specific binding is detected using a horseradish peroxidase-conjugated goat anti-rabbit anti-body followed by tyramide labeling with green-fluorescent Alexa Fluor 488 for 1 h at room temperature in accordance with the manufacturer's instructions.

FICZ improves the atopic dermatitis-like skin inflammation, clinical scores, and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduces the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduces the gene expression of Il22.^[2]