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.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.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.doi http://dx.doi.org/10.1038/s41598-021-83757-1
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/46923
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Scientific Reports. 2021 Feb 25;11(1):4715
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-79956-R
  • 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.accessRights info:eu-repo/semantics/openAccess
  • 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.type.version info:eu-repo/semantics/publishedVersion

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