Efficacy of Berberine‐Mediated Photodynamic Therapy Against Trichophyton rubrum Infection

Objective To investigate the antifungal effects of berberine‐mediated photodynamic therapy (BBR‐PDT) against Trichophyton rubrum ( T. rubrum ) both in vitro and in vivo, and to elucidate its underlying mechanisms of action. Methods The minimum inhibitory concentration (MIC) of BBR‐PDT against T. rubrum was determined according to the CLSI M38‐A2 guidelines. The MTT assay was used to evaluate the effects of various BBR concentrations and light doses, with results subsequently validated by colony diameter measurements and spore germination assays. Intracellular reactive oxygen species (ROS) levels were measured using DCFH‐DA, and transmission electron microscopy (TEM) was used to assess cellular damage in T. rubrum . A guinea pig skin infection model was established, and therapeutic efficacy was evaluated using clinical skin scoring, fungal culture, and histopathological analysis (H&E staining). Results In vitro experiments showed that at a light dose of 96 J/cm 2 , the MIC of BBR was 12 μg/mL. Neither light irradiation alone nor BBR monotherapy exhibited antifungal activity. Combined treatment with 12 μg/mL BBR and 72 J/cm 2 blue light significantly inhibited radial hyphal growth and spore germination of T. rubrum . Mechanistic investigations revealed that BBR‐PDT significantly increased ROS levels within spores, and T. rubrum exhibited extensive cellular damage, including membrane rupture, cell wall loosening, cytoplasmic vacuolization, and organelle degeneration. In the guinea pig model, BBR‐PDT significantly reduced scaling, promoted hair regrowth, and improved clinical skin scores. Fungal colony counts from skin cultures were significantly reduced, and H&E staining demonstrated restoration of normal skin structure. Conclusion BBR‐PDT exerts antifungal effects via ROS‐mediated oxidative stress. This oxidative stress disrupts T. rubrum ultrastructure through multiple mechanisms. The therapy is effective against T. rubrum in vitro and in vivo. Therefore, BBR‐PDT holds promise as a treatment for dermatophyte infections.