Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination

Autor: Estefanía Butassi, Maximiliano Sortino, Juan Carlos Ribas, Susana Zacchino, Laura Svetaz, Vanessa S. D. Carvalho, Ariel D. Quiroga, Juan Carlos G. Cortés
Přispěvatelé: Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Universidad Nacional de Rosario (Argentina), Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Svetaz, Laura A., Cortés, Juan C.G., Ribas, Juan C., Svetaz, Laura A. [0000-0002-1023-1641], Cortés, Juan C.G. [0000-0002-2395-6668], Ribas, Juan C. [0000-0001-6430-0895]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Antifungal Agents
Fungal membrane
MODE OF ANTIFUNGAL ACTION
Pharmaceutical Science
Virulence
Germ tube
Microbial Sensitivity Tests
Cell wall
03 medical and health sciences
chemistry.chemical_compound
FUNGAL MEMBRANE
0302 clinical medicine
ZUCCAGNIA PUNCTATA-LARREA NITIDA COMBINATION
Amphotericin B
Ergosterol
Candida albicans
Drug Discovery
Humans
Viability assay
SYNERGISM
030304 developmental biology
FUNGAL CELL WALL
Pharmacology
0303 health sciences
Plants
Medicinal
biology
Virulence factors
Plant Extracts
Chemistry
Mode of antifungal action
Zuccagnia punctata-Larrea nitida combination
Synergism
Ciencias Químicas
Fabaceae
Chitin synthase
Larrea
Corpus albicans
Yeast
Química Orgánica
Complementary and alternative medicine
Biochemistry
030220 oncology & carcinogenesis
Fungal cell wall
biology.protein
Molecular Medicine
VIRULENCE FACTORS
CIENCIAS NATURALES Y EXACTAS
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Popis: [Background] In our previous study the synergism of four combinations of Zuccagnia punctata (ZpE) and Larrea nitida (LnE) exudates with the reliable statistical-based MixLow method was assessed, and the markers of the most anti-C. albicans synergistic ZpE-LnE bi-herbal combination were quantified according to European Medicines Agency (EMA).
[Purpose] To study 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) and rate of killing of ZpE-LnE were assessed with the microbroth dilution and the time-kill assays respectively. Morphological alterations were observed with both confocal and fluorescence microscopy on the yeast Schizosaccharomyces pombe. The ergosterol exogenous assay, the quantification of ergosterol, the sorbitol as well as glucan synthase (GS) and chitin synthase (ChS) assays were used to detect the effects on the fungal membrane and cell wall respectively. The capacity of ZpE-LnE of inhibiting Candida virulence factors was assessed with previously reported methods. The effect of ZpE-LnE and of ZpE or LnE alone on cell viability was determined on human hepatoma cells line Huh7.
[Results] ZpE-Ln E was fungicidal killing C. albicans in a shorter time than amphotericin B and produced malformations in S. pombe cells. ZpE-LnE showed to bind to ergosterol but not to inhibit any step of the ergosterol biosynthesis. ZpE-LnE showed a low or moderate capacity of inhibiting GS and ChS. Regarding inhibition of virulence factors, ZpE-LnE significantly decreased the capacity of adhesion to eukaryotic buccal epithelial cells (BECs), did not inhibit the germ tube formation and 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.
[Conclusion] 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, make ZpE-LnE a good candidate for the development of a new antifungal bi-Herbal Medicinal Product.
S.Z. and M.S. acknowledge Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), PICT2014-1170 and PICT2016-1833 and National University of Rosario, Argentina (UNR) for funds. J.C.R. acknowledges MINECO (BIO2015-69958-P) and Junta de Castilla y León (CSI068P17), Spain for funds. A.D.Q. acknowledges ANPCyT (PICT2013-1440) and UNR for funds. E.B. acknowledges Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) for a doctoral fellowship. M.S., L.S. and A.D.Q. are members of the CONICET Researcher career; M.S., L.S., and E.B. belong to the teaching staff of Pharmacognosy area and M.S. belongs to the teaching staff of Mycological Area Faculty of Biochemical and Pharmaceutical Sciences, UNR.
Databáze: OpenAIRE
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