title: Fungicidal effect of isoquercitrin via inducing membrane disturbance.
abstract: Isoquercitrin is a flavonoid isolated from Aster yomena, which has been used as a traditional medicinal herb. In the present study, we investigated the antifungal activity and the underlying mechanism of isoquercitrin. Isoquercitrin had a potent effect in the susceptibility test against pathogenic fungi and almost no hemolysis. Propidium iodide and potassium release assays were conducted in Candida albicans, and these studies confirmed that isoquercitrin induced membrane damage, thereby, increasing permeability. Membrane potential was analyzed using 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)], and the transition of membrane potential was indicated by an increased fluorescence intensity. To further analyze these results using model membranes, giant unilamellar vesicles and large unilamellar vesicles that encapsulated calcein were prepared and the detection of calcein leakage from liposomes indicated that membrane was disturbed. We further verified membrane disturbance by observing the disordered status of the lipid bilayer with 1,6-diphenyl-1,3,5-hexatriene fluorescence. Moreover, changes in size and granularity of the cell were revealed in flow cytometric analysis. All these results suggested the membrane disturbance and the degree of disturbance was estimated to be within a range of 2.3 nm to 3.3 nm by fluorescein isothiocyanate-dextran analysis. Taken together, isoquercitrin exerts its fungicidal effect by disturbing the membrane of cells.
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: JiEun
authors.initials: J
authors.lastname: Yun
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Heejeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Hae Ju
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.affiliation: School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea. Electronic address: dglee222@knu.ac.kr.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D031173:Aster Plant / Q000737:chemistry*; D052160:Benzothiazoles; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D002232:Carbocyanines; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003911:Dextrans; D004161:Diphenylhexatriene; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010946:Plants, Medicinal; D011794:Quercetin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D056910:Republic of Korea; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D052160:Benzothiazoles; D002232:Carbocyanines; D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D053835:Unilamellar Liposomes; C015219:fluorescein isothiocyanate dextran; C016527:isoquercitrin; D004161:Diphenylhexatriene; C012944:3,3'-dipropyl-2,2'-thiadicarbocyanine; D011794:Quercetin; D016650:Fluorescein-5-isothiocyanate; C007740:fluorexon
keywords: Antifungal activity; Isoquercitrin; Membrane disturbance; Phytochemical