title: In vitro antifungal activity of baicalin against Candida albicans biofilms via apoptotic induction.
abstract: The aim of this study was to investigate the antifungal activity of baicalin and its potential mechanism of action against Candida albicans biofilms. The standard techniques including microdilution method and checkerboard assay were employed to evaluate the susceptibilities of baicalin alone and in combination with fluconazole against planktonic and biofilm cells of C. albicans. Transmission electron microscope (TEM), scanning electron microscope (SEM), fluorescent microscope and flow cytometry were used to assess the apoptotic incidences induced by baicalin in biofilm cells. The expressions of four genes (RAS1, CAP1, PDE2 and TPK1) related to Ras-cAMP-PKA pathway were also analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results showed that minimum inhibitory concentration (MIC) and sessile minimum inhibitory concentration (SMIC50) of baicalin were 500 and 2000 μg/mL with fractional inhibitory concentration indexs (FICIs) ranging from 0.28 to 0.75. A series of events related to apoptosis were observed in baicalin-treated C. albicans biofilms, including extensive chromatin condensation along the nuclear envelope, ROS accumulation, MMP reduction, PS externalization, nuclear fragmentation, chromatin condensation, metacaspase activation and Cyt C release. Additionally, the expressions of RAS1 and TPK1 were up-regulated by 3.2 and 2.9 folds respectively, while those of CAP1 and PDE2 were down-regulated by 3.3 and 6.6 folds respectively after exposure to baicalin in biofilm cells. In conclusion, baicalin can suppress the development of C. albicans biofilms most likely due to inducing cell death via apoptosis.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: TianMing
authors.initials: T
authors.lastname: Wang
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: GaoXiang
authors.initials: G
authors.lastname: Shi
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China. Electronic address: sq@ahtcm.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Shao
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: DaQiang
authors.initials: D
authors.lastname: Wu
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: YuanYuan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: MengXiang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: YanYan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei 230038, China. Electronic address: wangchangzhong53@126.com.
authors.forename: ChangZhong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology*; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D015725:Fluconazole / Q000494:pharmacology; D020869:Gene Expression Profiling; D008826:Microbial Sensitivity Tests; D008853:Microscopy
chemical_list: D000935:Antifungal Agents; D005419:Flavonoids; C038044:baicalin; D015725:Fluconazole
keywords: Antifungal activity; Apoptosis; Baicalin; Biofilms; Candida albicans; Ras-cAMP-PKA