title: Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.
abstract: Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms.
authors.affiliation: a Department of Dentistry , State University of Paraiba , Campina Grande , PB , Brazil ;
authors.forename: Jozinete Vieira
authors.initials: JV
authors.lastname: Pereira
authors.affiliation: b Division of Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences , Piracicaba Dental School, University of Campinas , Piracicaba , SP , Brazil ;
authors.forename: Irlan Almeida
authors.initials: IA
authors.lastname: Freires
authors.affiliation: b Division of Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences , Piracicaba Dental School, University of Campinas , Piracicaba , SP , Brazil ;
authors.forename: Aline Rogéria
authors.initials: AR
authors.lastname: Castilho
authors.affiliation: b Division of Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences , Piracicaba Dental School, University of Campinas , Piracicaba , SP , Brazil ;
authors.forename: Marcos Guilherme
authors.initials: MG
authors.lastname: da Cunha
authors.affiliation: c Department of Pharmacy , State University of Paraiba , Campina Grande , PB , Brazil.
authors.forename: Harley da Silva
authors.initials: Hda S
authors.lastname: Alves
authors.affiliation: b Division of Pharmacology, Anesthesiology and Therapeutics, Department of Physiological Sciences , Piracicaba Dental School, University of Campinas , Piracicaba , SP , Brazil ;
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Rosalen
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal; D000067996:RAW 264.7 Cells; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology; D029632:Sapotaceae / Q000737:chemistry; D027842:Syzygium / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D005419:Flavonoids; D010936:Plant Extracts; D012503:Saponins
keywords: Antifungals; flavonoids; natural products; saponins