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dc.contributor.author
Butassi, Estefanía  
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Svetaz, Laura Andrea  
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Sortino, Maximiliano Andrés  
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Quiroga, Ariel Dario  
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Carvalho, Vanessa S. D.  
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Cortés, Juan C. G.  
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Ribas, Juan C.  
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Zacchino, Susana Alicia Stella  
dc.date.available
2020-11-26T14:58:23Z  
dc.date.issued
2019-02  
dc.identifier.citation
Butassi, Estefanía; Svetaz, Laura Andrea; Sortino, Maximiliano Andrés; Quiroga, Ariel Dario; Carvalho, Vanessa S. D.; et al.; Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination; Elsevier Gmbh; Phytomedicine; 54; 2-2019; 291-301  
dc.identifier.issn
0944-7113  
dc.identifier.uri
http://hdl.handle.net/11336/119104  
dc.description.abstract
Background: In our previous study we assessed the synergism of four combinations of Zuccagnia punctata (ZpE) and Larrea nitida (LnE) with the reliable statistical-based MixLow method and found the most anti-C. albicans synergistic ZpE-LnE bi-herbal combination whose composition was quantified by a valid method, according to European Medicines Agency (EMA). Purpose: The purpose of this research was to advance in the study of the mechanisms of action as well as the cytotoxic properties of the ZpE-LnE most synergistic combination found in the previous work. Materials and methods: Minimum Fungicidal Concentration (MFC) of ZpE-LnE was assessed with the microbroth dilution method of the Clinical and Laboratory Standard Institute (CLSI) and the rate of killing was determined with the time-kill assay in the range 0?24h. The morphological alterations were observed with both confocal and fluorescence microscopies on the model yeast Schizosaccharomyces pombe. The ergosterol exogenous assay, the quantification of ergosterol, the sorbitol assay as well as glucan synthase (GS) and chitin synthase (ChS) assays were used to detect the inhibition of the fungal membrane and cell wall respectively. The capacity of ZpE-LnE of inhibiting Candida virulence factors such as adherence to buccal epithelial cells (BECs), germ tube inhibition, and inhibition of phospholipases, proteinases and haemolysins secretion, were assessed with previously reported methods. The effect of ZpE-LnE and each ZpE or LnE alone on cell viability against human hepatoma cell line Huh7 was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. Results: ZpE-LnE was fungicidal rather than fungistatic, killing C. albicans in a shorter time than amphotericin B (AmpB). ZpE-LnE produced malformations in S. pombe cells likely due to a damage in the plasma membrane or the cell wall. ZpE-LnE showed to bind to the membrane ergosterol in the exogenous ergosterol assay, but not to inhibit any step of the ergosterol biosynthesis. ZpE-LnE showed a low or moderate capacity of inhibiting GS and ChS of the fungal cell wall. Regarding the effect on virulence factors, ZpE-LnE significantly decreased the capacity of adhesion to eukaryotic BECs, did not inhibit the germ tube formation and completely inhibited the secretion of phospholipases and proteinases but not of haemolysins. ZpE-LnE demonstrated very low toxicity on Huh7 cells, much lower than that each extract alone. Conclusions: The fungicidal properties of ZpE-LnE against C. albicans, its dual mechanism of action targeting the fungal membrane´s ergosterol as well as the cell wall, its capacity of inhibiting several important virulence factors added to its low toxicity, makes this combination a good candidate for the development of a new antifungal bi-Herbal Medicinal Product.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Elsevier Gmbh  
dc.rights
info:eu-repo/semantics/restrictedAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
MODE OF ANTIFUNGAL ACTION  
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ZUCCAGNIA PUNCTATA-LARREA NITIDA COMBINATION  
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FUNGAL CELL WALL  
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FUNGAL MEMBRANE  
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VIRULENCE FACTORS  
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SYNERGISM  
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Química Orgánica  
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Ciencias Químicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2020-07-01T20:38:49Z  
dc.journal.volume
54  
dc.journal.pagination
291-301  
dc.journal.pais
Alemania  
dc.journal.ciudad
Berlín  
dc.description.fil
Fil: Butassi, Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina  
dc.description.fil
Fil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina  
dc.description.fil
Fil: Sortino, Maximiliano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro de Estudios Fotosintéticos y Bioquímicos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina  
dc.description.fil
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina  
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Fil: Carvalho, Vanessa S. D.. Instituto de Biología Funcional y Genómica; España. Consejo Superior de Investigaciones Científicas; España  
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Fil: Cortés, Juan C. G.. Instituto de Biología Funcional y Genómica; España. Consejo Superior de Investigaciones Científicas; España  
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Fil: Ribas, Juan C.. Instituto de Biología Funcional y Genómica; España. Consejo Superior de Investigaciones Científicas; España  
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Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina  
dc.journal.title
Phytomedicine  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0944711318302356  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.phymed.2018.06.045