title: Paeonia lactifloraInhibits Cell Wall Synthesis and Triggers Membrane Depolarization inCandida albicans.
abstract: Fungal cell walls and cell membranes are the main targets of antifungals. In this study, we report on the antifungal activity of an ethanol extract fromPaeonia lactifloraagainstCandida albicans, showing that the antifungal activity is associated with the synergistic actions of preventing cell wall synthesis, enabling membrane depolarization, and compromising permeability. First, it was shown that the ethanol extract fromP. lactiflorawas involved in damaging the integrity of cell walls inC. albicans. In isotonic media, cell bursts ofC. albicansby theP. lactifloraethanol extract could be restored, and the minimum inhibitory concentration (MIC) of theP. lactifloraethanol extract againstC. albicanscells increased 4-fold. In addition, synthesis of (1,3)-β-D-glucan polymer was inhibited by 87% and 83% following treatment ofC. albicansmicrosomes with theP. lactifloraethanol extract at their 1× MIC and 2× MIC, respectively. Second, the ethanol extract fromP. lactiflorainfluenced the function ofC. albicanscell membranes.C. albicanscells treated with theP. lactifloraethanol extract formed red aggregates by staining with a membrane-impermeable dye, propidium iodide. Membrane depolarization manifested as increased fluorescence intensity by stainingP. lactiflora-treatedC. albicanscells with a membrane-potential marker, DiBAC4(3) ((bis-1,3-dibutylbarbituric acid) trimethine oxonol). Membrane permeability was assessed by crystal violet assay, andC. albicanscells treated with theP. lactifloraethanol extract exhibited significant uptake of crystal violet in a concentration-dependent manner. The findings suggest thatP. lactifloraethanol extract is a viable and effective candidate for the development of new antifungal agents to treatCandida-associated diseases.
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejongsi 30019, Republic of Korea.
authors.forename: Heung-Shick
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Korean Medicine, Semyung University, Jecheon 27136, Republic of Korea.
authors.forename: Younhee
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001463:Barbiturates; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects* / Q000473:pathology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002473:Cell Wall / Q000187:drug effects*; D000431:Ethanol; D005840:Gentian Violet / Q000494:pharmacology; D007555:Isoxazoles; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008861:Microsomes / Q000187:drug effects; D029596:Paeonia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011419:Propidium / Q000494:pharmacology; D011509:Proteoglycans; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001463:Barbiturates; D007555:Isoxazoles; D010936:Plant Extracts; D011509:Proteoglycans; D047071:beta-Glucans; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol; D011419:Propidium; D000431:Ethanol; C010770:polysaccharide-K; D005840:Gentian Violet
keywords: Antifungal; Candida albicans; Paeonia lactiflora; cell wall; membrane permeability; membrane potential