Antifungal compounds from Zanthoxylum schinifolium seeds against tinea pedis fungus: Isolation, identification and mechanism of action.

Tinea pedis, a common superficial cutaneous fungal infection, substantially affects patients' quality of life and may also lead to complications such as secondary infections. Zanthoxylum schinifolium (ZS) seeds, a traditional dual-purpose resource with medicinal and culinary uses, possess various pharmacological properties, including lipid-lowering, antioxidant, and antibacterial effects. However, the specific active components and mechanisms underlying their inhibitory activities against tinea pedis remain unclear. This is the first study to isolate and identify four active compounds (fargesin, kobusin, prudomestin, and sesamin) from ZS seeds with inhibitory activities against tinea pedis. In vitro antifungal experiments demonstrated that these compounds exhibited significant inhibitory effects on Trichophyton rubrum and Trichophyton interdigitale, with kobusin showing the most potent antifungal activity, as indicated by a minimum inhibitory concentration of 0.039 mg/mL against both pathogens. Further studies revealed that kobusin inhibits spore germination and hyphal growth, disrupts cell membrane integrity and potential, and causes leakage of nucleic acids and proteins. Simultaneously, it causes severe damage to hyphal morphology and structure while inducing lipid peroxidation and reactive oxygen species accumulation, coupled with the suppression of antioxidant enzyme activity, ultimately triggering oxidative stress-mediated hyphal apoptosis. Additionally, it disrupts the cellular respiratory chain and energy metabolism, resulting in the comprehensive inhibition of the normal growth of T. rubrum. Notably, kobusin exhibits low cytotoxicity toward HEK 293 and RAW 264.7 cells. This study provides an important theoretical foundation for the development of ZS seeds as a natural antifungal agent.