Label-Free Quantitative Proteomic Analysis of 4-Aminopyridine-Induced Pruritic Skin in Mice Intervened by Trans-Nerolidol

Introduction: Essential oil of Cinnamomum camphora possesses antipruritic effects, and trans-nerolidol may be one of its active constituents. The proteomic analysis of itch mice induced by 4-aminopyridine (4-AP) and the effects of trans-nerolidol were investigated to delineate the possible underlying mechanism. Methods: Proteomic analysis of mouse skin was carried out using label-free nano LC-ESIOrbiTrap MS/MS technology. The biological information of differentially expressed proteins was analyzed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Animal behavior and skin histopathology were also observed. Results: Itch mice exhibited a licking reaction and skin inflammation, which were alleviated by trans-nerolidol. A total of 219 differentially expressed proteins were identified. Nine significant differential proteins, including Ephrin type-A receptor 2 (EphA2) and Zinc finger and BTB domain-containing protein 7A (Zbtb7a), were selected for further analysis. Discussions: EphA2 forward signaling can inhibit the MAPK pathway and LTB4 production to relieve itching. Zbtb7a might regulate the MAPK signaling pathway. EphA2 was validated, showing negative expression in the model group and positive expression in normal and transnerolidol administered groups. Conclusion: Trans-nerolidol demonstrated an antipruritic effect, and EphA2 and Zbtb7a are likely targets for the treatment of pruritus.