Kirenol, a diterpene active component from Siegesbeckia orientalis, alleviates atopic dermatitis by suppressing TYK2

作者：Chen Z, Wang Y, Guo H, Huang Z, Chen L, Dai W, Chen J, Zheng J, Liang Q, Xu W, Li X · 发表于：International immunopharmacology · 年份：2026 · DOI：10.1016/j.intimp.2026.116938 · 研究领域：Dermatitis, Atopic、TYK2 Kinase、Diterpenes、Anti-Inflammatory Agents、Sigesbeckia、Animals、Humans、Mice、RAW 264.7 Cells、Male、Dinitrochlorobenzene、Molecular Docking Simulation

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by severe pruritus, skin barrier dysfunction, and underlying immune dysregulation. Kirenol, a major active ingredient and quality control marker from Siegesbeckia orientalis L., has been shown to possess broad pharmacological properties, ranging from anti-arthritic and anti-tumor activities to therapeutic potential in cardiovascular medicine. However, its effect on atopic dermatitis has not yet been reported. AIM OF THE STUDY: This study aims to investigate the therapeutic efficacy and underlying molecular mechanisms of Kirenol in the treatment of atopic dermatitis. METHODS: ScRNA-seq data from skin tissues of 5 AD patients and 4 healthy donors was analyzed by Seurat in R. The direct interaction between Kirenol and Tyrosine Kinase 2 (TYK2) was assessed using molecular docking and cellular thermal shift assays (CETSA). In vitro, the anti-inflammatory mechanisms of Kirenol were evaluated in RAW264.7 murine macrophages and HaCaT human immortalized keratinocytes. In vivo, an AD murine model was established via 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. The therapeutic efficacy of Kirenol was evaluated based on clinical scoring and histological analysis. RESULTS: ScRNA-seq data analysis demonstrated that TYK2 expression was elevated in keratinocytes and macrophages of atopic dermatitis patients. Molecular docking and CETSA analyses confirmed that Kirenol directly...