Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.

<h4>Background</h4>Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergis...

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Autores principales: Janina K Hellmann, Sylvia Münter, Michael Wink, Friedrich Frischknecht
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:f129cbd08d4b4d59a51d7463f29d46ee2021-11-25T06:26:48ZSynergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.1932-620310.1371/journal.pone.0008682https://doaj.org/article/f129cbd08d4b4d59a51d7463f29d46ee2010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20072627/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergistic effects between such potential drug candidates and adjuvants. To probe for such effects, we tested the green tea compound epigallocatechin gallate (EGCG) and the membrane permeabilising digitonin on Plasmodium sporozoite motility and viability.<h4>Methodology/principal findings</h4>Green fluorescent P. berghei sporozoites were imaged using a recently developed visual screening methodology. Motility and viability parameters were automatically analyzed and IC50 values were calculated, and the synergism of drug and adjuvant was assessed by the fractional inhibitory concentration index. Validating our visual screening procedure, we showed that sporozoite motility and liver cell infection is inhibited by EGCG at nontoxic concentrations. Digitonin synergistically increases the cytotoxicity of EGCG on sporozoite survival, but shows an additive effect on sporozoite motility.<h4>Conclusions/significance</h4>We proved the feasibility of performing highly reliable visual screens for compounds against Plasmodium sporozoites. We thereby could show an advantage of administering mixtures of plant metabolites on inhibition of cell motility and survival. Although the effective concentration of both drugs is too high for use in malaria prophylaxis, the demonstration of a synergistic effect between two plant compounds could lead to new avenues in drug discovery.Janina K HellmannSylvia MünterMichael WinkFriedrich FrischknechtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8682 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Janina K Hellmann
Sylvia Münter
Michael Wink
Friedrich Frischknecht
Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
description <h4>Background</h4>Most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. However, little is known about synergistic effects between such potential drug candidates and adjuvants. To probe for such effects, we tested the green tea compound epigallocatechin gallate (EGCG) and the membrane permeabilising digitonin on Plasmodium sporozoite motility and viability.<h4>Methodology/principal findings</h4>Green fluorescent P. berghei sporozoites were imaged using a recently developed visual screening methodology. Motility and viability parameters were automatically analyzed and IC50 values were calculated, and the synergism of drug and adjuvant was assessed by the fractional inhibitory concentration index. Validating our visual screening procedure, we showed that sporozoite motility and liver cell infection is inhibited by EGCG at nontoxic concentrations. Digitonin synergistically increases the cytotoxicity of EGCG on sporozoite survival, but shows an additive effect on sporozoite motility.<h4>Conclusions/significance</h4>We proved the feasibility of performing highly reliable visual screens for compounds against Plasmodium sporozoites. We thereby could show an advantage of administering mixtures of plant metabolites on inhibition of cell motility and survival. Although the effective concentration of both drugs is too high for use in malaria prophylaxis, the demonstration of a synergistic effect between two plant compounds could lead to new avenues in drug discovery.
format article
author Janina K Hellmann
Sylvia Münter
Michael Wink
Friedrich Frischknecht
author_facet Janina K Hellmann
Sylvia Münter
Michael Wink
Friedrich Frischknecht
author_sort Janina K Hellmann
title Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
title_short Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
title_full Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
title_fullStr Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
title_full_unstemmed Synergistic and additive effects of epigallocatechin gallate and digitonin on Plasmodium sporozoite survival and motility.
title_sort synergistic and additive effects of epigallocatechin gallate and digitonin on plasmodium sporozoite survival and motility.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/f129cbd08d4b4d59a51d7463f29d46ee
work_keys_str_mv AT janinakhellmann synergisticandadditiveeffectsofepigallocatechingallateanddigitoninonplasmodiumsporozoitesurvivalandmotility
AT sylviamunter synergisticandadditiveeffectsofepigallocatechingallateanddigitoninonplasmodiumsporozoitesurvivalandmotility
AT michaelwink synergisticandadditiveeffectsofepigallocatechingallateanddigitoninonplasmodiumsporozoitesurvivalandmotility
AT friedrichfrischknecht synergisticandadditiveeffectsofepigallocatechingallateanddigitoninonplasmodiumsporozoitesurvivalandmotility
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