Journal
RESEARCH IN MICROBIOLOGY
Volume 161, Issue 7, Pages 534-540Publisher
ELSEVIER
DOI: 10.1016/j.resmic.2010.05.002
Keywords
Punica granatum; Candida albicans; Synergism; Punicalagin; Antifungal activity; Electron microscopy
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Financiadora de Estudos e Projetos (FINEP)
- Capacitacao e Aperfeicoamento de Pessoal de Nivel Superior, (Capes)
- Fundacao Araucaria, and Programa de Pos-graduacao em Ciencias Farmaceuticas da Universidade Estadual de Maringa
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Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal activity against Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against Candida albicans and Candida parapsilosis, with MICs of 3.9 and 1.9 mu g/ml, respectively. The combination of punicalagin and fluconazole showed a synergistic interaction. MIC for fluconazole decreased twofold when combined with the extract. The FIG index was 0.25. The synergism observed in disk-diffusion and checkerboard assays was confirmed in time-kill curves. The effect of punicalagin on the morphology and ultrastructure in treated yeast cells was examined by scanning and transmission electron microscopy. An irregular budding pattern and pseudohyphae were seen in treated yeasts. By transmission electron microscopy, treated cells showed a thickened cell wall, changes in the space between cell wall and the plasma membrane, vacuoles, and a reduction in cytoplasmic content. Since the punicalagin concentration effective in vitro is achievable in vivo, the combination of this agent with fluconazole represents an attractive prospect for the development of new management strategies for candidiasis, and should be investigated further in in vivo models. Crown Copyright (C) 2010 Published by Elsevier Masson SAS. All rights reserved.
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