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Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

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dc.contributor.author Starbuck, John M.
dc.contributor.author Llambrich, Sergi
dc.contributor.author González, Rubén
dc.contributor.author Albaigès-Ràfols, Júlia
dc.contributor.author Sarlé, Anna
dc.contributor.author Wouters, Jens
dc.contributor.author González, Alejandro
dc.contributor.author Sevillano, Xavier
dc.contributor.author Sharpe, James
dc.contributor.author Torre Fornell, Rafael de la
dc.contributor.author Dierssen, Mara
dc.contributor.author Velde, Greetje Vande
dc.contributor.author Martínez Abadías, Neus
dc.date.accessioned 2021-03-24T09:12:19Z
dc.date.available 2021-03-24T09:12:19Z
dc.date.issued 2021
dc.identifier.citation Starbuck JM, Llambrich S, Gonzàlez R, Albaigès J, Sarlé A, Wouters J et al. Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome. Sci Rep. 2021 Feb 25;11(1):4715. DOI: 10.1038/s41598-021-83757-1
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/46923
dc.description.abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
dc.description.sponsorship We acknowledge support from a 2016 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation IN[16]_CMA_BIO_0096 (NMA). We also acknowledge grant support from the following: CRG Awards for Collaborative Research Proposals, CRG Awards 2015-005822 (NMA, JA), Marguerite-Marie Delacroix Foundation fellowship (SL), Jerome Lejeune Foundation, #1782 (GVV, NMA), University of Central Florida start-up funds (JMS), American Association of Physical Anthropologists Professional Development Program Grant (JMS), Flemish Research Foundation (FWO) fellowship (GVV), and KU Leuven IF STG/15/024 (GVV), MINECO SAF2016-79956-R (MD), and the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Scientific Reports. 2021 Feb 25;11(1):4715
dc.rights © John M. Starbuck et al 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Te verd
dc.subject.other Down, Síndrome de
dc.title Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41598-021-83757-1
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-79956-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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