title: Isolation of (-)-olivil-9'-O-β-d-glucopyranoside from Sambucus williamsii and its antifungal effects with membrane-disruptive action.
abstract: In this study, we isolated (-)-olivil-9'-O-β-d-glucopyranoside (OLI9G), a phytochemical from the stem bark of Sambucus williamsii, and investigated the antifungal mechanism of OLI9G against Candida albicans. First of all, the antifungal susceptibility testing and hemolysis assay showed that OLI9G exerted a potent activity without hemolysis compared to the activity of amphotericin B. To investigate the mechanism of action of OLI9G, we first examined membrane depolarization using cyanine dye, 3,3'-dipropylthiacarbocyanine iodide (diSC35). The results showed that OLI9G significantly changed the fungal membrane potential. To further understand this activity on the membrane, we did the propidium iodide (PI) influx assay. From the results, OLI9G caused membrane permeabilization in the fungal membrane, and the three dimensional (3D) flow cytometric contour plot from the PI influx assay further showed that the cells had shrunk due to the membrane damage. Finally, the membrane-active mechanism of OLI9G was confirmed by synthesizing a model membrane, calcein-encapsulating large unilamellar vesicles (LUVs). The calcein leakage showed the membrane-disruptive effects caused by direct action of OLI9G. In conclusion, the current study suggests that OLI9G exerts its antifungal activity through a membrane-disruptive action.
authors: College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea. dglee222@knu.ac.kr
authors: Hyemin
authors: H
authors: Choi
authors: Juneyoung
authors: J
authors: Lee
authors: Young Su
authors: YS
authors: Chang
authors: Eun-Rhan
authors: ER
authors: Woo
authors: Dong Gun
authors: DG
authors: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D005658:Fungi / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D027923:Sambucus / Q000737:chemistry*; D053835:Unilamellar Liposomes
chemical_list: D000935:Antifungal Agents; D005452:Fluoresceins; D017705:Lignans; D053835:Unilamellar Liposomes; C476392:olivil; C007740:fluorexon