Anticapsular and Antifungal Activity of α-Cyperone

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.

α-Cyperone Protects Cardiomyocytes against Oxygen-Glucose Deprivation-Induced Inflammation and Oxidative Stress by Akt/FOXO3a/NF-κB Pathway

“…α -Cyperone is one of the main components of Cyperus rotundus oil and has diversified beneficial biological activities [ 5 ]. Related studies have exhibited that α -cyperone exerts antidepressant effects by enhancing neuroplasticity in mice through inhibition of SIRT3/reactive oxygen species- (ROS-) mediated NLRP3 inflammasomes [ 6 ].…”

Alpiniae oxyphylla fructus extract promotes longevity and stress resistance of C. elegans via DAF-16 and SKN-1

“…( Zhang H et al, 2021 ).The study found that atalpha-cyperone as a fungicidal antifungal agent that can synergize with the activity of a fluconazole antifungal drug that can be used in combination antifungal therapy and some results showed that atalpha-cyperone exerted neuroprotective effects against H 2 O 2 -induced cell apoptosis in SH-SY5Y cells. ( Horn and Vediyappan, 2021 ). As an Organic acids, it has been reported that gluconic acid can also be considered a marker of oxidative stress and some results indicated that supplementation with glucose oxidase could increase antioxidant capacity, immune function and improve the intestinal microbiota composition of broilers.…”

Emerging Antifungal Targets and Strategies

“…Mayer and Kronstad [ 126 ] demonstrated inhibitory effect of Bacillus safensis , which potently blocked several key C. neoformans virulence factors, such as reduction in overall cell size and completely block fungal capsule formation. α-Cyperone, from the rhizome of Cyperus rotundus , could be used for the interference with Cryptococcus morphology since it reduces the thickness of capsule in C. neoformans [ 97 ].…”