Sodium new houttuyfonate inhibits the growth of Trichophyton spp. by potentially inducing oxidative stress and metabolic disruption.

INTRODUCTION: Dermatophytes are a group of common pathogenic fungi that infect the skin, nails, and hair of humans and other animals, affecting approximately 25% of the global human population. Their antifungal resistance has intensified, underscoring the urgent need for novel antifungal agents. Sodium new houttuyfonate (SNH), a derivative of the Houttuynia cordata Thunb., a plant native to Southeast Asian, shows broad-spectrum antimicrobial activity, but its effects on dermatophytes are unclear. METHODS: The in vitro activity of SNH against Trichophyton mentagrophytes standard strain ATCC MYA-4439 and Trichophyton rubrum clinical strain S136 was evaluated through broth dilution assays, growth assays on solid medium, conidia germination rate assessments, biomass quantification, reactive oxygen species (ROS) production assay, with its mechanism further investigated by RNA-seq and qPCR. RESULTS: SNH exhibited a minimum inhibitory concentration of 100 μg/ml against both strains, significantly suppressing colony expansion, conidia germination, biomass and promoting the production of ROS. Transcriptome analysis revealed SNH upregulated peroxisome biogenesis gene (PEX5) while downregulating superoxide dismutase (SOD), and dysregulated key energy metabolism genes (ICL, HK, GLU). DISCUSSION: These findings demonstrate that SNH possesses potent antifungal activity against dermatophytes, primarily by disrupting redox homeostasis and interfering with energy metabolism. This provides a theoretical basis for its potential development as an antifungal agent.