Thuja sutchuenensis Franch. Essential Oil Ameliorates Atopic Dermatitis Symptoms in Mice by Modulating Skin Microbiota Composition and Reducing Inflammation.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by dysregulated immunity, skin barrier dysfunction, and cutaneous microbiome dysbiosis. While current therapies face limitations, Thuja sutchuenensis essential oil (TEO) shows promise due to its multi-target potential. We sought to explore the beneficial effects of TEO and delve into its mechanistic actions in a mouse model of AD. We combined network pharmacology with in vivo validation to evaluate the therapeutic efficacy and mechanisms of TEO in an AD model, and confirmed network-predicted targets in an in vitro inflammatory cell model. In AD mice, TEO alleviated pruritus and epidermal hyperplasia, suppressed systemic IL-4/TNF-α and IgE, and partially normalized serum ALB, LDL-C, and HDL-C. Microbial diversity increased after treatment, although potentially pathogenic taxa (Arthrobacter sp. and Corynebacterium mastitidis) remained enriched. Machine-learning analysis indicated the highest predicted metabolic activity in CK controls, whereas the AD and TEO groups showed elevated pathogenic phenotype scores. Network pharmacology prioritized active compounds [(E)-ligustilide, senkyunolide A, 3-butylisobenzofuran-1(3H)-one, butylated hydroxytoluene, Z-buthlidenephthalide, and β-Myrcene] and core targets (TNF, PTPRC, CCR5, JAK1), implicating T-cell receptor signaling, Staphylococcus aureus infection, and STAT3 pathways. Docking and molecular dynamics supported strong, stable binding of major constituents to JAK1, and Western blotting confirmed TEO-mediated inhibition of the JAK1/STAT3 axis. TEO effectively alleviates atopic dermatitis symptoms by modulating immune responses and enhancing microbial diversity. It targets key signaling pathways, such as JAK1/STAT3, highlighting its potential as a therapeutic option for AD.