Sclareolide as Antifungal Strategy Against Cryptococcus neoformans: Unveiling Its Mechanisms of Action

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorSIMTS-
Autor(es): dc.contributorUniversity of Atacama-
Autor(es): dc.contributorCIT-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidad Tecnológica Metropolitana (UTEM)-
Autor(es): dc.creatorGaneshkumar, Arumugam-
Autor(es): dc.creatorLima, Patricia Michelle Nagai de-
Autor(es): dc.creatorHaribabu, Jebiti-
Autor(es): dc.creatorBorges, Bruno Montanari-
Autor(es): dc.creatorPreite, Nycolas Willian-
Autor(es): dc.creatorLoures, Flavio Vieira-
Autor(es): dc.creatorArulraj, Arunachalam-
Autor(es): dc.creatorJunqueira, Juliana Campos-
Data de aceite: dc.date.accessioned2025-08-21T16:42:12Z-
Data de disponibilização: dc.date.available2025-08-21T16:42:12Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/microorganisms12112324-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/309329-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/309329-
Descrição: dc.descriptionCryptococcal infection commonly begins as an opportunistic infection in humans, however, this can escalate to a systemic or life-threatening form in immunocompromised individuals. Here, we aim to identify novel antifungal molecules from plants resources. Sclareolide, a phytochemical classified as a sesquiterpene lactone, was assessed against Cryptococcus neoformans H99. Sclareolide exhibited promising antifungal properties with a minimum inhibitory concentration (MIC) of 16 µg/mL. Additionally, the C. neoformans growth rate was significantly affected by sclareolide treatment in a concentration-dependent manner, as observed through a time killing assay, with a significant reduction at MIC × 8 compared to the control by 48 h. To elucidate the underlying mechanisms of sclareolide antifungal activity, fluorescence-based methods were employed. Propidium iodide (PI) accumulation assay indicated a reduction in C. neoformans membrane integrity, with values as low as 6.62 ± 0.18% after treatment. Moreover, sclareolide at MIC × 4 and MIC × 8 significantly increased the production of reactive oxygen species (ROS) and reduced the mitochondrial membrane potential (MMP), suggesting oxidative stress and mitochondrial dysfunction in C. neoformans. Sclareolide did not induce caspase-dependent apoptosis, suggesting a non-apoptotic mechanism. Further, a checkerboard experiment was performed to assess potential synergistic interaction with Amphotericin B, however, no synergism was observed. Moving on, sclareolide at 128 µg/mL did not exhibit toxicity in Galleria mellonella, further supporting its potential as a safe antifungal agent. These findings suggest that the antifungal activity of sclareolide against C. neoformans is mediated by oxidative stress. Further in vivo and pharmacokinetic studies are recommended to explore the potential of sclareolide as a prototype for the development of novel anti-cryptococcal therapies.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionUniversidad de Atacama-
Descrição: dc.descriptionDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology Sao Paulo State University (UNESP)-
Descrição: dc.descriptionDepartment of Materials Physics Saveetha School of Engineering Saveetha Institute of Medical and Technical Sciences SIMTS, Chennai, Tamil Nadu-
Descrição: dc.descriptionFaculty of Medicine University of Atacama, Los Carreras 1579-
Descrição: dc.descriptionChennai Institute of Technology CIT, Tamil Nadu-
Descrição: dc.descriptionInstitute of Science and Technology Federal University of Sao Paulo (UNIFESP)-
Descrição: dc.descriptionDepartamento de Electricidad Facultad de Ingeniería Universidad Tecnológica Metropolitana (UTEM), Av. José Pedro Alessandri 1242, Santiago-
Descrição: dc.descriptionDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology Sao Paulo State University (UNESP)-
Descrição: dc.descriptionCAPES: CAPES-88887.890668/2023-00-
Descrição: dc.descriptionUniversidad de Atacama: DIUDA-88231R3-
Idioma: dc.languageen-
Relação: dc.relationMicroorganisms-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectantifungals-
Palavras-chave: dc.subjectCryptococcus-
Palavras-chave: dc.subjectphytochemicals-
Palavras-chave: dc.subjectROS and MMP-
Palavras-chave: dc.subjectsclareolide-
Título: dc.titleSclareolide as Antifungal Strategy Against Cryptococcus neoformans: Unveiling Its Mechanisms of Action-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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