Antifungal activity and mechanistic insights of total alkaloids from <i>Sophora flavescens</i> against <i>Candida albicans</i>

<i>Candida albicans</i> 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. <i>Sophora flavescens</i>, 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 <i>S. flavescens</i> (TASF) against <i>C. albicans</i>. 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 (<i>HWP1</i>, <i>ALS3</i>, <i>ECE1</i>, and <i>NRG1</i>) and upregulation of <i>TEC1</i>, suggesting inhibition of hyphal transition. These findings highlight TASF as a promising candidate for the development of new antifungal therapies.