Antifungal activity of Punicalagin–nystatin combinations against Candida albicans
Rafaela Alves da Silva
Integrated Research Center, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Investigation, Methodology, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorBella Luna Colombini Ishikiriama
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorMarcelo Milanda Ribeiro Lopes
Integrated Research Center, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Investigation, Writing - original draft
Search for more papers by this authorRicardo Dias de Castro
Department of Clinical and Social Dentistry, Federal University of Paraíba, Castelo Branco III, João Pessoa, Brazil
Contribution: Methodology, Validation, Writing - original draft
Search for more papers by this authorCindy Ruiz Garcia
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorVinicius Carvalho Porto
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Formal analysis, Writing - original draft
Search for more papers by this authorCarlos Ferreira Santos
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Funding acquisition, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Karin Hermana Neppelenbroek
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Correspondence
Karin Hermana Neppelenbroek, Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, 17012-901 Bauru, São Paulo, Brazil.
Email: [email protected]
Contribution: Project administration, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorVanessa Soares Lara
Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorRafaela Alves da Silva
Integrated Research Center, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Investigation, Methodology, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorBella Luna Colombini Ishikiriama
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Investigation, Writing - review & editing
Search for more papers by this authorMarcelo Milanda Ribeiro Lopes
Integrated Research Center, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Investigation, Writing - original draft
Search for more papers by this authorRicardo Dias de Castro
Department of Clinical and Social Dentistry, Federal University of Paraíba, Castelo Branco III, João Pessoa, Brazil
Contribution: Methodology, Validation, Writing - original draft
Search for more papers by this authorCindy Ruiz Garcia
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorVinicius Carvalho Porto
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Formal analysis, Writing - original draft
Search for more papers by this authorCarlos Ferreira Santos
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Funding acquisition, Writing - original draft, Writing - review & editing
Search for more papers by this authorCorresponding Author
Karin Hermana Neppelenbroek
Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Correspondence
Karin Hermana Neppelenbroek, Department of Prosthodontics and Periodontics, Bauru School of Dentistry, University of São Paulo (USP), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, 17012-901 Bauru, São Paulo, Brazil.
Email: [email protected]
Contribution: Project administration, Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorVanessa Soares Lara
Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of Dentistry, University of São Paulo (USP), Bauru, Brazil
Contribution: Conceptualization, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
Search for more papers by this authorAbstract
Objectives
Oral candidiasis is the most common opportunistic fungal infection of oral mucosa and results from an overgrowth of Candida, especially Candida albicans. The potential anti-C. albicans and cytotoxicity of punicalagin (PCG), isolated from Punica granatum, alone or with nystatin (NYS) were evaluated.
Methods
Activity of compounds alone or in combinations was determined against two C. albicans strains (ATCC 90028 and SC5314). Minimal inhibitory concentration (MIC)-50 and Minimum Fungicidal Concentration (MFC) were assessed by XTT assay and CFU counts, respectively. For combinations, determination of fractional inhibitory concentration index was performed. Ergosterol pathway was investigated as a possible PCG antifungal mechanism. Cytotoxicity assays were undertaken on human primary oral keratinocytes and gingival fibroblasts incubated with antifungal concentrations of PCG and/or NYS for 24 hr.
Results
Combination of NYS and PCG increased antifungal efficacy, compared with compounds tested alone. Combinations 4 (PCG-6.25 μg/ml; NYS-3.9 μg/ml) and 5 (PCG-12.5 μg/ml; NYS-1.95 μg/ml) were more effective since they reduced the MIC-50 of PCG (50 μg/ml) by 8 and 4 times, respectively, increased the candidal inhibition and nullified the PCG cytotoxicity for keratinocytes. PCG antifungal mechanism did not involve ergosterol biosynthesis pathway.
Conclusions
The favorable outcomes for combination of PCG and NYS encourage further testing this therapeutic strategy against C. albicans.
CONFLICTS OF INTEREST
None to declare.
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