Potent In Vitro Synergism of Fluconazole and Osthole against Fluconazole-Resistant Candida albicans
Open accessAbstract
Osthole is a natural coumarin that exhibits wide biological and pharmacological activities such as neuroprotective, osteogenic, immunomodulation, antitumor, and anti-inflammatory effects. In this study, we investigated the antifungal effects of osthole in vitro . A checkerboard microdilution assay showed that osthole has significant synergistic effect with fluconazole against fluconazole-resistant Candida albicans . Similar results were obtained from a growth curve assay. Meanwhile, XTT reduction assay demonstrated the synergism of fluconazole and osthole against C. albicans biofilm formation. Microarray results showed that the expression of genes involved in the oxidation-reduction process, energy metabolism, and transportation changed significantly after the combined treatment with fluconazole and osthole, and further results showed that endogenous reactive oxygen species (ROS) was significantly increased in the combination group. In conclusion, these results demonstrate the synergism of fluconazole and osthole against fluconazole-resistant C. albicans and indicate that endogenous ROS augmentation might contribute to the synergism of fluconazole and osthole.
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Baicalin, berberine, and osthole can elevate ROS levels in C. albicans, thereby bolstering antifungal potency of azoles.
“Our previous investigations have demonstrated that baicalin, berberine, and osthole can elevate ROS levels in C. albicans, thereby bolstering the antifungal potency of azoles58–60.”
From Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities (2025) · cites this paper as [60]
The Results report that osthole elevated ROS in C. albicans and that combining it with fluconazole produced a larger ROS increase. The Introduction and Discussion report antifungal synergy, but say ROS augmentation *might* contribute to it; they do not establish the claim’s causal “thereby.” This paper supports the osthole portion of the multi-citation sentence, not the claims about baicalin or berberine. (LLM, conf=0.86)
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“Our previous investigations have demonstrated that baicalin, berberine, and osthole can elevate ROS levels in C. albicans , thereby bolstering the antifungal potency of azoles 58 – 60 .”
Self-citation
- Authors
- Li, D.-D., Chai, D., Huang, X.-W., Guan, S.-X., Du, J., Zhang, H.-Y., Sun, Y., & Jiang, Y.-Y.
- Affiliations
- Clinical Pharmacy Center, Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
- Chinese PLA General Hospital (CN)
- Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China
- ORCID
- Sun, Yan
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2017-08
- Volume
- 61
- Issue
- 8
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5527582
- OpenAlex
- W2626051938
- Cited by
- 42
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 10 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 1
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81573724, 81501730)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Food Science › Essential Oils and Antimicrobial Activity
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- osthole, fluconazole, Candida albicans, antifungal synergy, fluconazole resistance, coumarins, biofilm formation, reactive oxygen species, gene expression profiling, combination antifungal therapy
- MeSH terms
- Antifungal Agents, Candida albicans, Candidiasis, Coumarins, Drug Synergism, Drug Therapy, Combination, Microbial Sensitivity Tests, Fluconazole, Gene Expression Regulation, Fungal, Reactive Oxygen Species, Oxidative Stress, Drug Resistance, Fungal
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