Naringin-generated ROS promotes mitochondria-mediated apoptosis in Candida albicans.

Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O ) and hydroxyl radicals (OH ). Reactive oxygen species (ROS) have a serious impact on Ca signaling and the production of mitochondrial ROS. After exposure to enhanced O and OH , mitochondrial Ca overload and mitochondrial O generation were confirmed in C. albicans. It was verified that mitochondrial O transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin-generated O and OH damage the mitochondria and that mitochondrial dysfunction-mediated apoptosis is novel antifungal mechanism of naringin.