Qingre Chushi decoction ameliorates MC903-induced atopic dermatitis in association with reduced JAK-STAT6 activation and decreased CD206+IL-31+ macrophage abundance.

Qingre Chushi Decoction (QRCSD) is a traditional Chinese medicine formula used clinically for atopic dermatitis (AD), whereas its immunological basis remains poorly understood. This study investigated the therapeutic effects and associated immune changes of QRCSD in an MC903-induced murine AD model. The chemical profile of QRCSD was characterized by UPLC-Q-TOF-MS/MS, and four representative marker compounds, including chlorogenic acid, gentiopicroside, baicalin, and glycyrrhizic acid, were quantitatively determined by targeted UPLC-MS/MS in MRM mode for quality control. AD-like lesions were induced in male C57BL/6 J mice by topical MC903 application. Dermatitis severity, scratching behavior, and transepidermal water loss were assessed, while epidermal barrier proteins, pruritogenic mediators, circulating cytokines, and immune-cell profiles were evaluated by histological analysis, immunofluorscence, ELISA, and flow cytometry. QRCSD markedly reduced dermatitis severity, epidermal thickness, TEWL, scratching behavior, and mast-cell infiltration, while restoring filaggrin and involucrin expression and reducing TSLP and IL-31 levels. Circulating IL-4, IL-13, IL-17 A, IL-6, TNF-α, IFN-γ, and total IgE were also decreased. Flow cytometry revealed altered T-cell profiles following QRCSD treatment. In the QRCSD-H group, reduced eosinophil and macrophage proportions and decreased CD206+IL-31+ macrophages were observed in lesional skin. Transcriptomic and protein analyses further demonstrated JAK-STAT-associated immune changes, including decreased phosphorylation of JAK1, JAK3, and STAT6, accompanied by reduced Arg1 and CD206 expression. Collectively, QRCSD ameliorated MC903-induced AD and was associated with restored epidermal barrier function, altered systemic and cutaneous immune responses, reduced CD206+IL-31+ macrophage abundance, and decreased JAK-STAT6 pathway activation. These findings provide a biological basis for the immunoregulatory effects of QRCSD in AD.