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Published on: January 13, 2023
Anticapsular and Antifungal Activity of α-Cyperone
Connor Horn1, Govindsamy Vediyappan1
1Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Abstract:
Fungal infections affect 300 million people and cause 1.5 million deaths globally per year. With the number of immunosuppressed patients increasing steadily, there is an increasing number of patients infected with opportunistic fungal infections such as infections caused by the species of Candida and Cryptococcus. In fact, the drug-resistant Can. krusei and the emerging pan-antifungal resistant Can. auris pose a serious threat to human health as the existing limited antifungals are futile. To further complicate therapy, fungi produce capsules and spores that are resistant to most antifungal drugs/host defenses. Novel antifungal drugs are urgently needed to fill unmet medical needs. From screening a collection of medicinal plant sources for antifungal activity, we have identified an active fraction from the rhizome of Cyperus rotundus, the nut grass plant. The fraction contained α-Cyperone, an essential oil that showed fungicidal activity against different species of Candida. Interestingly, the minimal inhibitory concentration of α-Cyperone was reduced 8-fold when combined with a clinical antifungal drug, fluconazole, indicating its antifungal synergistic potential and could be useful for combination therapy. Furthermore, α-Cyperone affected the synthesis of the capsule in Cryp. neoformans, a causative agent of fungal meningitis in humans. Further work on mechanistic understanding of α-Cyperone against fungal virulence could help develop a novel antifungal agent for drug-resistant fungal pathogens.
Insights
A natural compound, α-Cyperone from Cyperus rotundus, shows potent antifungal activity against Candida species and inhibits capsule formation in Cryptococcus neoformans, offering a potential new strategy for drug-resistant fungal infections.
Area of Science:
- Mycology
- Pharmacology
- Natural Product Chemistry
Background:
- Fungal infections cause 1.5 million deaths annually, with rising threats from drug-resistant species like Candida auris.
- Opportunistic fungal infections are increasing in immunosuppressed populations.
- Existing antifungal drugs are limited and often ineffective against fungal capsules and spores.
Purpose of the Study:
- To identify novel antifungal agents from medicinal plants.
- To investigate the antifungal activity of compounds from Cyperus rotundus.
- To explore the potential of α-Cyperone in combination therapy and against fungal virulence factors.
Main Methods:
- Screening of medicinal plant extracts for antifungal activity.
- Isolation and identification of active compounds, specifically α-Cyperone.
- Testing α-Cyperone's fungicidal activity against Candida species.
- Evaluating the synergistic effect of α-Cyperone with fluconazole.
- Assessing α-Cyperone's impact on Cryptococcus neoformans capsule synthesis.
Main Results:
- An active fraction from Cyperus rotundus rhizome containing α-Cyperone demonstrated fungicidal activity against Candida species.
- α-Cyperone showed an 8-fold reduction in minimal inhibitory concentration when combined with fluconazole, indicating synergy.
- α-Cyperone inhibited capsule synthesis in Cryptococcus neoformans.
Conclusions:
- α-Cyperone is a promising candidate for novel antifungal drug development.
- Combination therapy with α-Cyperone and fluconazole could enhance treatment efficacy.
- α-Cyperone's ability to disrupt fungal capsules suggests potential against virulent fungal pathogens.
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