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揭示新见解:香叶醇对多重耐药念珠菌菌株增强的抗念珠菌功效及作用机制创新

Unveiling novel insights: geraniol's enhanced anti-candida efficacy and mechanistic innovations against multidrug-resistant candida strains.

作者信息

da Silva Lisandra Juvêncio, Rodrigues Daniel Sampaio, de Farias Cabral Vitória Pessoa, da Silva Cecília Rocha, Sá Lívia Gurgel do Amaral Valente, de Andrade-Neto João Batista, Barbosa Amanda Dias, Flaresso Amanda Arrais, Rocha Sânia Nara Costa da, Cavalcanti Bruno Coelho, Moraes Manoel Odorico de, Rios Maria Erivanda França, Pampolha Filho Iri Sandro, Júnior Hélio Vitoriano Nobre

机构信息

School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.

Center for Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil.

出版信息

Braz J Microbiol. 2024 Dec;55(4):3721-3731. doi: 10.1007/s42770-024-01498-5. Epub 2024 Sep 19.

Abstract

OBJECTIVES

This study addressed the need for new treatments for severe Candida infections, especially resistant strains. It evaluated the antifungal potential of geraniol alone and with fluconazole against various Candida spp., including resistant strains, and investigated geraniol's mechanism of action using flow cytometry.

METHODS

The research assessed the inhibitory effects of geraniol on the growth of various Candida species at concentrations ranging from 110 to 883 µg/ml. The study also explored the potential synergistic effects when geraniol was combined with fluconazole. The mechanism of action was investigated through flow cytometry, with a particular emphasis on key enzymes associated with plasma membrane synthesis, membrane permeability changes, mitochondrial membrane depolarization, reactive oxygen species (ROS) induction, and genotoxicity.

RESULTS

Geraniol demonstrated significant antifungal activity against different Candida species, inhibiting growth at concentrations within the range of 110 to 883 µg/ml. The mechanism of action appeared to be multifactorial. Geraniol was associated with the inhibition of crucial enzymes involved in plasma membrane synthesis, increased membrane permeability, induction of mitochondrial membrane depolarization, elevated ROS levels, and the presence of genotoxicity. These effects collectively contributed to cell apoptosis.

CONCLUSIONS

Geraniol, alone and in combination with fluconazole, shows promise as a potential therapeutic option for Candida spp.

INFECTIONS

Its diverse mechanism of action, impacting crucial cellular processes, highlights its potential as an effective antifungal agent. Further research into geraniol's therapeutic applications may aid in developing innovative strategies to address Candida infections, especially those resistant to current therapies.

摘要

目的

本研究满足了对严重念珠菌感染(尤其是耐药菌株)新治疗方法的需求。它评估了香叶醇单独以及与氟康唑联合对包括耐药菌株在内的各种念珠菌属的抗真菌潜力,并使用流式细胞术研究了香叶醇的作用机制。

方法

该研究评估了香叶醇在110至883微克/毫升浓度范围内对各种念珠菌生长的抑制作用。该研究还探索了香叶醇与氟康唑联合时的潜在协同作用。通过流式细胞术研究作用机制,特别关注与质膜合成、膜通透性变化、线粒体膜去极化、活性氧(ROS)诱导和遗传毒性相关的关键酶。

结果

香叶醇对不同念珠菌属表现出显著的抗真菌活性,在110至883微克/毫升浓度范围内抑制生长。作用机制似乎是多因素的。香叶醇与抑制参与质膜合成的关键酶、增加膜通透性、诱导线粒体膜去极化、升高ROS水平以及存在遗传毒性有关。这些作用共同导致细胞凋亡。

结论

香叶醇单独以及与氟康唑联合,显示出作为念珠菌属感染潜在治疗选择的前景。其多样的作用机制影响关键细胞过程,突出了其作为有效抗真菌剂的潜力。对香叶醇治疗应用的进一步研究可能有助于开发创新策略来应对念珠菌感染,尤其是那些对当前疗法耐药的感染。

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