lignans and Candidiasis

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.. 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.. 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.. 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.

Topics: Antifungal Agents; Biphenyl Compounds; Candida albicans; Candidiasis; Electron Transport Complex I; Fungal Proteins; Gene Expression Regulation, Fungal; Humans; Lignans; Magnolia; Oxidative Stress; Superoxides

Styraxjaponoside C was investigated with respect to its antifungal activity and mechanisms of action. Devoid of hemolytic activity, Styraxjaponoside C demonstrated an antifungal effect against the human pathogenic yeast Candida albicans in an energy-independent manner. To characterize the mechanisms of the antifungal activity of Styraxjaponoside C, fluorescence analysis with membrane probe 1,6-diphenyl-1,3,5-hexatriene, and flow cytometric analysis on C. albicans were conducted. The results showed that Styraxjaponosdie C induced cytoplasmic membrane perturbation. The current study suggested that Styraxjaponoside C was active against C. albicans with membrane-active mechanisms.

Topics: Antifungal Agents; Candida albicans; Candidiasis; Cell Membrane; Colony Count, Microbial; Diphenylhexatriene; Energy Metabolism; Fluorescent Dyes; Glucosides; Humans; Lignans; Magnetic Resonance Spectroscopy; Mycelium; Plant Bark; Plant Extracts; Styrax

To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida albicans.. A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of C. albicans. In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK. In the in vitro study, synergism was observed in all 24 FLC-resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by Delta E models. No antagonistic activity was observed in any of the strains tested. These positive interactions were also confirmed by using the time-killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC. In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study.. Synergistic activity of HNK and FLC against clinical isolates of FLC-resistant C. albicans was observed in vitro and in vivo.. This report might provide a potential therapeutic method to overcome the problem of drug-resistance in C. albicans.

Topics: Animals; Antifungal Agents; Biphenyl Compounds; Candida albicans; Candidiasis; Colony Count, Microbial; Drug Resistance, Fungal; Drug Synergism; Fluconazole; Humans; Lignans; Mice; Microbial Sensitivity Tests; Microbial Viability; Treatment Outcome