| Abstrakt: |
Background: Honokiol, a compound extracted from Magnolia officinalis, has antifungal activities by inducing mitochondrial dysfunction and triggering apoptosis in Candida albicans. However, the mechanism of honokiol-induced oxidative stress is poorly understood. The present investigation was designed to determine the specific mitochondrial reactive oxygen species (ROS)-generation component. Methods/results: We found that honokiol induced mitochondrial ROS accumulation, mainly superoxide anions (O2•−) measured by fluorescent staining method. The mitochondrial respiratory chain complex I (C I) inhibitor rotenone completely blocked O2•− production and provided the protection from the killing action of honokiol. Moreover, respiratory activity and the C I enzyme activity was significantly reduced after honokiol treatment. The differential gene-expression profile also showed that genes involved in oxidoreductase activity, electron transport, and oxidative phosphorylation were upregulated. Conclusions: The present work shows that honokiol may bind to mitochondrial respiratory chain C I, leading to mitochondrial dysfunction, accompanied by increased cellular superoxide anion and oxidative stress. General significance: This work not only provides insights on the mechanism by which honokiol interferes with fungal cell, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of M. officinalis as a Chinese medicine due to the toxic for mitochondria and suggests the possibility of using honokiol as chemosensitizer. [ABSTRACT FROM AUTHOR] |
