Opposite effects of vitamin C and vitamin E on the antifungal activity of honokiol

Abstract

The aim of the present study was to evaluate the effects of two well-known natural antioxidants, vitamin C (VC) and vitamin E (VE), on the antifungal activity of honokiol against Candida albicans. The broth microdilution method was employed to test the antifungal activities of honokiol with or without antioxidants in the medium against C. albicans strain. Intracellular reactive oxygen species and lipid peroxidation were determined by fluorescence staining assay. Mitochondrial dysfunction was assessed by detecting the mitochondrial DNA and the mitochondrial membrane potential. We observed that VC could significantly potentiate the antifungal activities of honokiol while VE reduced the effectiveness of honokiol against C. albicans. In addition, VC accelerated honokiol-induced mitochondrial dysfunction and inhibited glycolysis leading to a decrease in cellular ATP. However, VE could protect against mitochondrial membrane lipid peroxidation and rescue mitochondrial function after honokiol treatment. Our research provides new insight into the understanding of the action mechanism of honokiol and VC combination against C. albicans.

Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans

“…More detailedly, VC potentiated the antifungal activity of KPA, while VE reduced its effectiveness against C. albicans. As reported in other antifungal natural products, such as honokiol, the molecular mechanisms of these opposite effects have been reported by Sun Lingmei et al [14]. This discovery reminds the synergistic or antagonistic effect between KPA and VC or VE again, which may guide the clinical application of KPA to avoid VE and combine VC.…”

“…DCFH-DA was used to detect the level of intracellular ROS as previously reported [13,14]. SC5314 cells were treated with series concentrations of KPA or 1 μg/mL of AMB (positive control) in SD medium.…”

“…Knowing that mitochondrial membrane potential (mtΔψ) and intracellular ATP levels are important indicators of the mitochondrial structure and function, we examined the effect of KPA on the alteration of mtΔψ and ATP content as previously reported with some modification [13,14]. SC5314 cells (1 × 10 6 cells/mL) were treated with different concentrations of KPA in SD medium at 30˚C for 3 h and then stained with 5 μM Rh123 for 30 min in the dark, after three times washes with sterile PBS, cells were measured with a BioTek Synergy2 spectrofluorophotometer at 486 nm excitation and 525 nm emission and observed with the Olympus BX53F fluorescence microscope.…”

“…This experiment was also carried out in the presence of 5 mM Tu as previously reported [13]. Intracellular ATP levels were measured according to the previously reported method [14]. Treated SC5314 cells were disrupted by vortexing with glass beads, and the intracellular ATP levels were determined using an ATP Assay kit (Beyotime, Haimen, Jiangsu, PR China) according to the provided protocol.…”

“…SC5314 cells (1 × 10 6 cells/mL) were pre-incubation with or without Tu (5 mM), VC (10 mM) or VE (10 mM) in SD medium respectively for 1 h at 30˚C according to previously described method [13,14]. KPA was then added with a final concentration of 16 μg/mL before the incubation at 30˚C for additional 3 h. Drug free treatments with or without Tu, VC or VE served as control groups.…”