title: Inhibitory effect of Shikonin on Candida albicans growth.
abstract: Our study showed that Shikonin (SK) could provide an action against almost all Candida albicans isolates tested. More importantly, to some Fluconazole (FCZ)-resistant Candida albicans, the action of SK (MIC(80) value 4 µg/mL) was shown to be >16 times higher than that of FCZ (MIC(80) >64 µg/mL). To clarify the mechanism underlying this action, we performed a comparative study in untreated control C. albicans and C. albicans treated with SK. In this study, we found that SK treatment increased generation of endogenous reactive oxygen species (ROS) and decreased mitochondrial membrane potential. Furthermore, anti-oxidants N-acetylcysteine (NAC) and glutathione (GSH) could reduce the antifungal activity of SK significantly in C. albicans. Our analyses also identified 9 differentially expressed genes, which were related to glycolysis-related genes (CDC19 and HXK2), fermentation-related genes (ALD5 and ADH1), antioxidant defense-related genes (SOD2 and SOD5), thioredoxin reductase-related gene (TRR1), mitochondrial respiratory electron transport chain-related gene (MRF1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidoreductase-related gene (EBP1). These results suggest that mitochondrial aerobic respiration shift and endogenous ROS augmentation contribute to the action of SK against C. albicans.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Miao
authors.forename: LiuYa
authors.initials: L
authors.lastname: Zhao
authors.forename: ChunLi
authors.initials: C
authors.lastname: Li
authors.forename: QingHua
authors.initials: Q
authors.lastname: Shang
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.forename: ZiJin
authors.initials: Z
authors.lastname: Fu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: YuanYing
authors.initials: Y
authors.lastname: Jiang
authors.forename: YingYing
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D005978:Glutathione / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; C016101:shikonin; D005978:Glutathione; D000111:Acetylcysteine