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Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination.
Phytomedicine. 2019 Feb 15; 54:291-301.P

Abstract

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.

Authors+Show Affiliations

Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina.Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina.Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina; Area Micología y Centro de Referencia en Micología (CEREMIC), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina.Area Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina; Instituto de Fisiología Experimental (IFISE), Consejo de Investigaciones Científicas y Técnicas (CONICET-UNR), Suipacha 531, 2000 Rosario, Argentina.Instituto de Biología Funcional y Genómica y Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, 37007 Salamanca, Spain.Instituto de Biología Funcional y Genómica y Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, 37007 Salamanca, Spain.Instituto de Biología Funcional y Genómica y Departamento de Microbiología y Genética, Consejo Superior de Investigaciones Científicas (CSIC)/Universidad de Salamanca, 37007 Salamanca, Spain.Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Argentina. Electronic address: szaabgil@citynet.net.ar.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30668380

Citation

Butassi, Estefanía, et al. "Approaches to the Mechanism of Antifungal Activity of Zuccagnia punctata-Larrea Nitida Bi-herbal Combination." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 54, 2019, pp. 291-301.
Butassi E, Svetaz LA, Sortino MA, et al. Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination. Phytomedicine. 2019;54:291-301.
Butassi, E., Svetaz, L. A., Sortino, M. A., Quiroga, A. D., Carvalho, V. S. D., Cortés, J. C. G., Ribas, J. C., & Zacchino, S. A. (2019). Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 54, 291-301. https://doi.org/10.1016/j.phymed.2018.06.045
Butassi E, et al. Approaches to the Mechanism of Antifungal Activity of Zuccagnia punctata-Larrea Nitida Bi-herbal Combination. Phytomedicine. 2019 Feb 15;54:291-301. PubMed PMID: 30668380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Approaches to the mechanism of antifungal activity of Zuccagnia punctata-Larrea nitida bi-herbal combination. AU - Butassi,Estefanía, AU - Svetaz,Laura A, AU - Sortino,Maximiliano A, AU - Quiroga,Ariel D, AU - Carvalho,Vanessa S D, AU - Cortés,Juan C G, AU - Ribas,Juan C, AU - Zacchino,Susana A, Y1 - 2018/07/06/ PY - 2018/04/26/received PY - 2018/06/20/revised PY - 2018/06/26/accepted PY - 2019/1/23/pubmed PY - 2019/6/25/medline PY - 2019/1/23/entrez KW - Fungal cell wall KW - Fungal membrane KW - Mode of antifungal action KW - Synergism KW - Virulence factors KW - Zuccagnia punctata-Larrea nitida combination SP - 291 EP - 301 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 54 N2 - 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. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/30668380/Approaches_to_the_mechanism_of_antifungal_activity_of_Zuccagnia_punctata_Larrea_nitida_bi_herbal_combination_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(18)30235-6 DB - PRIME DP - Unbound Medicine ER -