Antifungal activity and mechanistic insights of total alkaloids from Sophora flavescens against Candida albicans

Candida albicans is a major opportunistic fungal pathogen that causes a wide spectrum of infections, adversely affecting both physical and mental health. The rising incidence of antifungal resistance underscores the urgent need for novel therapeutic agents. Sophora flavescens, a traditional Chinese medicinal herb known for its antimicrobial and anti-inflammatory properties, has shown potential as an antifungal agent. This study evaluated the antifungal activity of total alkaloids from S. flavescens (TASF) against C. albicans. TASF demonstrated potent antifungal effects with an MIC of 40 mg/mL and MFC of 80 mg/mL. It induced intracellular ROS accumulation, impaired biofilm formation, and reduced cell adhesion. SEM analysis revealed significant morphological damage, including membrane rupture. Gene expression analysis indicated downregulation of virulence-associated genes (HWP1, ALS3, ECE1, and NRG1) and upregulation of TEC1, suggesting inhibition of hyphal transition. These findings highlight TASF as a promising candidate for the development of new antifungal therapies.