Honokiol kills Candida albicans through ROS accumulation and cell membrane destruction

Abstract:

[Objective] To investigate the inhibitory effect of honokiol on Candida albicans in vitro. [Methods] The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of magnolol for C. albicans were determined by microdilution method. Transmission electron microscopy was used to examine the effect of different concentrations of honokiol on the ultrastructure of C. albicans. Apoptosis of C. albicans caused by honokiol was analyzed by Annexin V-FITC/propidium iodide (PI) double staining and the accumulation of reactive oxygen species (ROS) in C. albicans cells was determined by DCFH-DA staining. The effects of honokiol on mitochondrial membrane potential and cell membrane permeability of C. albicans were analyzed by JC-1 staining and PI staining respectively. [Results] Honokiol had strong inhibitory effect on C. albicans, with MIC₉₀ of 16 µg/mL and MFC of 32 µg/mL. Honokiol affected cell wall, cell membrane, and cytoplasm of C. albicans, induced both apoptosis and necrosis in C. albicans, probably through ROS production and disruption of mitochondrial function. It also changed the permeability of cell membrane, leaded to the cell wall damage and the binding of ergosterol. [Conclusion] Inhibition of C. albicans by honikiol involves multiple mechanisms including ROS production accompanied by a series of cellular damages. Honikiol appears to be a potential antifungal drug candidate.