Effects and Mechanisms of Lonicerin Against Atopic Dermatitis: An Integration of Bioinformatics Analysis and Experimental Validation

Abstract

ABSTRACT Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin condition that significantly diminishes the quality of life for affected individuals. Lonicerin (LON), a natural bioflavonoid, possesses immunomodulatory and anti‐inflammatory properties. Nevertheless, the potential protective effects of LON on AD, in addition to the underlying mechanisms involved, remain to be elucidated. In the current study, we investigated the therapeutic effects of LON in an AD mouse model induced by 1‐chloro‐2,4‐dinitrobenzene (DNCB) and tumor necrosis factor (TNF)‐α/interferon gamma (IFN)‐γ stimulated HaCaT cells. The results showed that LON significantly mitigated AD manifestations, such as restricting mast cell, CD4 + T, and CD8 + T cell infiltration, inhibiting serum IgE and IL‐6 concentrations, improving epidermis and dermis thicknesses, histamine release, scratching behavior, SCORAD index, and restoring epidermal barrier proteins. LON also reduced the expression levels of proinflammatory cytokines and chemokines in dorsal skin tissues and HaCaT cells. The analysis of the GSE32924 database, in conjunction with network pharmacology, disclosed that PPARα, JAK2, and STAT1 may potentially be the targets accountable for the therapeutic efficacy of LON. Furthermore, transcriptomics, immunofluorescence staining, PCR, Western blotting, and siRNA transfection, along with antagonist combinations, confirmed that LON regulated the skin inflammatory response involving PPARα activation and STAT1 inhibition. Taken together, our studies indicate that LON can suppress AD‐like skin inflammation both in vivo and in vitro. These findings imply that LON may serve as a possible alternative therapeutic treatment for AD or other skin‐related inflammatory diseases.

Affiliated Institutions

• Affiliated Hospital of Southwest Medical University CN
• Southwest Medical University CN
• Sichuan University CN

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