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Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of g...

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Detalles Bibliográficos
Autores principales: Pazin, W.M., Vilanova, N., Voets, I.K., Soares, A.E.E., Ito, A.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Associação Brasileira de Divulgação Científica 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437936/
https://www.ncbi.nlm.nih.gov/pubmed/30916221
http://dx.doi.org/10.1590/1414-431X20198281
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author Pazin, W.M.
Vilanova, N.
Voets, I.K.
Soares, A.E.E.
Ito, A.S.
author_facet Pazin, W.M.
Vilanova, N.
Voets, I.K.
Soares, A.E.E.
Ito, A.S.
author_sort Pazin, W.M.
collection PubMed
description It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (l(o)) and liquid-disordered (l(d)) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of l(o) phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.
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spelling pubmed-64379362019-04-17 Effects of artepillin C on model membranes displaying liquid immiscibility Pazin, W.M. Vilanova, N. Voets, I.K. Soares, A.E.E. Ito, A.S. Braz J Med Biol Res Research Article It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (l(o)) and liquid-disordered (l(d)) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of l(o) phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface. Associação Brasileira de Divulgação Científica 2019-03-25 /pmc/articles/PMC6437936/ /pubmed/30916221 http://dx.doi.org/10.1590/1414-431X20198281 Text en https://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pazin, W.M.
Vilanova, N.
Voets, I.K.
Soares, A.E.E.
Ito, A.S.
Effects of artepillin C on model membranes displaying liquid immiscibility
title Effects of artepillin C on model membranes displaying liquid immiscibility
title_full Effects of artepillin C on model membranes displaying liquid immiscibility
title_fullStr Effects of artepillin C on model membranes displaying liquid immiscibility
title_full_unstemmed Effects of artepillin C on model membranes displaying liquid immiscibility
title_short Effects of artepillin C on model membranes displaying liquid immiscibility
title_sort effects of artepillin c on model membranes displaying liquid immiscibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437936/
https://www.ncbi.nlm.nih.gov/pubmed/30916221
http://dx.doi.org/10.1590/1414-431X20198281
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