A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington’s disease
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 29, 2021
- Source ID
- 10.1371/journal.pone.0254834
Entities
People
- Alexis Rivas
- Alfredo Sagredo
- Andrés Barriga
- Carla Delporte
- Claudio Hetz
- César Cárdenas
- Ivette Seguel
- Jose Luis Ordoñez
- Philippe Pihán
- Rene L. Vidal
- Rodrigo Pérez-Arancibia
- Ulises Ahumada
Organizations
- Air Force Office of Scientific Research
- FONDEF
- Instituto Millenium
- National Fund for Scientific and Technological Development
- The Michael J. Fox Foundation