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Synergistic Antifungal Activity of Isoquercitrin: Apoptosis and Membrane Permeabilization Related to Reactive Oxygen Species in Candida albicans
Author(s) -
Kim Suhyun,
Woo EunRhan,
Lee Dong Gun
Publication year - 2019
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1973
Subject(s) - reactive oxygen species , candida albicans , oxidative stress , superoxide dismutase , antioxidant , apoptosis , chemistry , biochemistry , antifungal drug , fluconazole , biology , microbiology and biotechnology , pharmacology , antifungal
Isoquercitrin (ISO), one of phytochemical isolated from aerial parts of Aster yomena , has been reported to have antifungal activity. However, the synergistic effect and the mechanism of ISO in combination with conventional antifungal agents are poorly understood. Therefore, synergistic antifungal effect between ISO and conventional antifungal agents was investigated. ISO at non‐antifungal concentration interacts synergistically with amphotericin B (AMB) and fluconazole (FLC), but the combination with flucytosine (5‐FC) showed no interaction. ISO disrupted an antioxidant system by inhibiting the activity of superoxide dismutase. This redox imbalance was shown to induce intracellular reactive oxygen species (ROS) accumulation and oxidative stress. ISO combined with FLC caused metacaspase activation and DNA condensation, markers of apoptosis, higher than the combination with ISO/AMB. In contrast, ISO with AMB synergistically stimulated membrane permeabilization compared to ISO/FLC. Scavenging ROS consequently reduced the synergy‐induced apoptosis and membrane permeabilization, indicating combinations induced ROS were associated with the synergy effect of ISO. In conclusion, AMB and FLC enhanced the antifungal potency of ISO through oxidative stress when used in synergy. © 2018 IUBMB Life, 71(1):283–292, 2019