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Cited by 105Antifungal resistance and susceptibilityMagnolia and Illicium researchEssential Oils and Antimicrobial Activity

Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction

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Sun, Lingmei, Liao, Kai, Hang, Chengcheng, Wang, Dayong·2017·PLOS ONE
DOI 10.1371/journal.pone.0172228PMC PMC5305218
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Abstract

OBJECTIVE: To investigate the effects of honokiol on induction of reactive oxygen species (ROS), antioxidant defense systems, mitochondrial dysfunction, and apoptosis in Candida albicans. METHODS: To measure ROS accumulation, 2',7'-dichlorofluorescein diacetate fluorescence was used. Lipid peroxidation was assessed using both fluorescence staining and a thiobarbituric acid reactive substances (TBARS) assay. Protein oxidation was determined using dinitrophenylhydrazine derivatization. Antioxidant enzymatic activities were measured using commercially available detection kits. Superoxide dismutase (SOD) genes expression was measured using real time RT-PCR. To assess its antifungal abilities and effectiveness on ROS accumulation, honokiol and the SOD inhibitor N,N'-diethyldithiocarbamate (DDC) were used simultaneously. Mitochondrial dysfunction was assessed by measuring the mitochondrial membrane potential (mtΔψ). Honokiol-induced apoptosis was assessed using an Annexin V-FITC apoptosis detection kit. RESULTS: ROS, lipid peroxidation, and protein oxidation occurred in a dose-dependent manner in C. albicans after honokiol treatment. Honokiol caused an increase in antioxidant enzymatic activity. In addition, honokiol treatment induced SOD genes expression in C. albicans cells. Moreover, addition of DDC resulted in increased endogenous ROS levels and potentiated the antifungal activity of honokiol. Mitochondrial dysfunction was confirmed by measured changes to mtΔψ. The level of apoptosis increased in a dose-dependent manner after honokiol treatment. CONCLUSIONS: Collectively, these results indicate that honokiol acts as a pro-oxidant in C. albicans. Furthermore, the SOD inhibitor DDC can be used to potentiate the activity of honokiol against C. albicans.

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Authors
Sun, L., Liao, K., Hang, C., & Wang, D.
Affiliations
Southeast University (CN)
Corresponding author
Wang, Dayong
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2017-02-13
Volume
12
Issue
2
Pages
e0172228
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0172228
PMC
PMC5305218
OpenAlex
W2589075635
Cited by
105
References
42
Citations by year
2026: 1 · 2025: 10 · 2024: 15 · 2023: 8 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 29 · 2018: 8 · 2017: 3
FWCI
10.53
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (CN) (81302814)
  • Jiangsu Province Natural Science Foundation (BK20130640, BK20140624)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Rehabilitation › Magnolia and Illicium research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Essential Oils and Antimicrobial Activity
Keywords
honokiol, Candida albicans, reactive oxygen species, apoptosis, mitochondrial dysfunction, superoxide dismutase, lipid peroxidation, protein oxidation, antioxidant enzymes, mitochondrial membrane potential, antifungal activity, N,N-diethyldithiocarbamate, pro-oxidants
MeSH terms
Allyl Compounds, Anti-Infective Agents, Biphenyl Compounds, Candida albicans, Ditiocarb, Dose-Response Relationship, Drug, Drug Synergism, Microbial Sensitivity Tests, Microscopy, Fluorescence, Mitochondria, Oxidation-Reduction, Phenols, Superoxide Dismutase, Lipid Peroxidation, Gene Expression Regulation, Fungal, Gene Expression Regulation, Enzymologic, Apoptosis, Reactive Oxygen Species, Lignans, Reverse Transcriptase Polymerase Chain Reaction, Membrane Potential, Mitochondrial

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