Ameliorative effects and mechanisms of paeonol against rosacea through network pharmacology and experimental validation.

Rosacea is a long-term and relapsing inflammatory skin disorder resulting from dysfunction of the immune and/or neurovascular systems. Paeonol (Pae), the primary active component extracted from Moutan Cortex, exhibits various pharmacological effects, including anti-inflammatory and antioxidant properties. This study aimed to evaluate the therapeutic efficacy of Paeonol in treating rosacea and to investigate the underlying mechanisms of its action. Bioinformatics analysis was employed to assess the overlap between rosacea pathogenesis and the pharmacological targets of Pae. An LL-37-induced rosacea-like mouse model was established to evaluate the therapeutic effects of Pae in vivo. Histopathological analysis was performed to assess skin lesions, angiogenesis, immune cell infiltration, and cytokine production. The involvement of the S100A9-NF-κB pathway was investigated to elucidate the molecular mechanism. Bioinformatics analysis predicted potential overlapping molecular targets between rosacea pathogenesis and paeonol.In vivo, Pae intervention markedly ameliorated rosacea-like skin lesions. Mechanistically, Pae suppressed the production of S100A9 through modulation of the LL-37 and NF-κB pathways. This study indicates that paeonol mitigates skin lesions in LL-37-induced rosacea-like mice, and these therapeutic effects are correlated with the modulation of the S100A9-NF-κB signaling axis, suggesting its potential as a promising candidate agent for rosacea-like inflammation intervention.