A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.

Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to...

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Autores principales:	Rodrigo Pérez-Arancibia, Jose Luis Ordoñez, Alexis Rivas, Philippe Pihán, Alfredo Sagredo, Ulises Ahumada, Andrés Barriga, Ivette Seguel, César Cárdenas, Rene L Vidal, Claudio Hetz, Carla Delporte
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09c5db5cd2124294b99d7d3027698aea
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spelling	oai:doaj.org-article:09c5db5cd2124294b99d7d3027698aea2021-12-02T20:08:56ZA phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.1932-620310.1371/journal.pone.0254834https://doaj.org/article/09c5db5cd2124294b99d7d3027698aea2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254834https://doaj.org/toc/1932-6203Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer´s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native U. molinae on reducing protein aggregation using cellular models of Huntington´s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19-1 genotype (ETE 19-1) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19-1 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from U. molinae berries that reduce the load of protein aggregates in living cells.Rodrigo Pérez-ArancibiaJose Luis OrdoñezAlexis RivasPhilippe PihánAlfredo SagredoUlises AhumadaAndrés BarrigaIvette SeguelCésar CárdenasRene L VidalClaudio HetzCarla DelportePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254834 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo Pérez-Arancibia Jose Luis Ordoñez Alexis Rivas Philippe Pihán Alfredo Sagredo Ulises Ahumada Andrés Barriga Ivette Seguel César Cárdenas Rene L Vidal Claudio Hetz Carla Delporte A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
description	Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer´s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native U. molinae on reducing protein aggregation using cellular models of Huntington´s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19-1 genotype (ETE 19-1) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19-1 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from U. molinae berries that reduce the load of protein aggregates in living cells.
format	article
author	Rodrigo Pérez-Arancibia Jose Luis Ordoñez Alexis Rivas Philippe Pihán Alfredo Sagredo Ulises Ahumada Andrés Barriga Ivette Seguel César Cárdenas Rene L Vidal Claudio Hetz Carla Delporte
author_facet	Rodrigo Pérez-Arancibia Jose Luis Ordoñez Alexis Rivas Philippe Pihán Alfredo Sagredo Ulises Ahumada Andrés Barriga Ivette Seguel César Cárdenas Rene L Vidal Claudio Hetz Carla Delporte
author_sort	Rodrigo Pérez-Arancibia
title	A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
title_short	A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
title_full	A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
title_fullStr	A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
title_full_unstemmed	A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.
title_sort	phenolic-rich extract from ugni molinae berries reduces abnormal protein aggregation in a cellular model of huntington's disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/09c5db5cd2124294b99d7d3027698aea
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A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.

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