Ferulic acid altered IL-17A/IL-17RA interaction and protected against imiquimod-induced psoriasis-like skin injury in mice

摘要

Ferulic acid (FA), a phenolic phytochemical, is commonly found in grains, vegetables, and fruits. Interleukin-17A (IL-17A) and IL-17 receptor A (IL-17RA) interaction is one of important therapeutic targets for psoriasis. Here we analyzed the FA effects on IL-17A/IL-17RA interaction and psoriasis-like skin injury induced by imiquimod (IMQ). IL-17A-blocking assay and docking analysis showed that FA interacted with Trp-67, Gln-94, and Glu-95 residues of IL-17A via hydrogen bonds and consequently abolished the binding of IL-17RA to IL-17A. Mice were topically given with IMQ and orally given with various amounts of FA for 14 consecutive days. FA attenuated IMQ-induced psoriasis-like skin lesions in a dose-dependent manner, and the epidermal thickness of mice treated with 100 mg/kg FA was reduced by 53.48 +/- 4.44% in comparison with sham, Global analysis of differentially expressed genes showed that IMQ and FA significantly affected immune response, metabolism, and mitogen-activated protein kinase signaling pathways. Immunohistochemical staining showed that FA inhibited the infiltration and the cytokine secretion of Th17 cell, dendritic cell, and granulocyte subsets in psoriatic skin tissues. In conclusion, we newly identified that oral administration of FA protected against IMQ-induced psoriatic skin injury in mice. Moreover, its protection was associated with the interference of IL-17A/IL-17RA interaction.