Therapeutic effects of jaceosidin on atopic dermatitis via ubiquitin-mediated JAK1 degradation
- Phytomedicine. 2026 Jun 17:159:158446. doi: 10.1016/j.phymed.2026.158446.
- 1. Dermatology Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- 2. Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
- 3. Dermatology Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: [email protected].
- 4. Dermatology Center, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China; Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: [email protected].
Background: Atopic dermatitis (AD) is a prevalent inflammatory skin disease with substantial clinical burden. Jaceosidin (JAC), a trihydroxy-dimethoxy flavone primarily isolated from Artemisia genus and several other Plants, possesses potent immunomodulatory and anti-inflammatory activities with therapeutic potential for inflammatory skin diseases. However, its precise anti-AD mechanism remains unclear.
Purpose: This study aimed to investigate the therapeutic efficacy of JAC against AD and elucidate its underlying mechanisms.
Methods: A murine AD model was established by repeated topical calcipotriol application, followed by topical JAC treatment for 7 consecutive days. Therapeutic efficacy was evaluated by ear thickness, dermatitis severity, and histopathology. TNF-α/IFN-γ-stimulated HaCaT cells and reconstructed human epidermis (RHE) models were further used for phenotypic validation and mechanistic analyses. RNA Sequencing, co-immunoprecipitation, and ubiquitination assays were performed.
Results: JAC significantly alleviated AD-like pathological manifestations in mice by reducing ear edema, mast cell infiltration, and Th2 cytokine production, while restoring epidermal barrier protein expression. Similar therapeutic effects were observed in TNF-α/IFN-γ-stimulated HaCaT cells and RHE models. Mechanistically, transcriptomic analysis identified SOCS4 as a key upstream regulator induced by JAC. JAC promoted SOCS4-mediated ubiquitin-proteasomal degradation of JAK1, leading to suppression of JAK1/STAT1 activation.
Conclusion: This study provides the first experimental evidence supporting the anti-AD effects of JAC across multiple preclinical models. JAC mitigates AD progression by restoring epidermal barrier integrity and modulating immune dysregulation through SOCS4-mediated degradation of JAK1 and subsequent suppression of JAK1/STAT signaling. These findings position JAC as a promising therapeutic candidate for AD.