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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.

SUBMITTER: Perez-Arancibia R

PROVIDER: S-EPMC8320977 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Pérez-Arancibia Rodrigo R Ordoñez Jose Luis JL Rivas Alexis A Pihán Philippe P Sagredo Alfredo A Ahumada Ulises U Barriga Andrés A Seguel Ivette I Cárdenas César C Vidal Rene L RL Hetz Claudio C Delporte Carla C

PloS one 20210729 7

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 fr ...[more]

PMID: 34324551

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Project description:Obesity is associated with metabolic abnormalities that increase the risk and severity of several diseases. This study aimed to explore whether the aqueous extract of Annona squamosa Linn leaves (ASE) can ameliorate metabolic abnormalities associated with high fat (HF) diet-induced obesity. Forty-eight male Wistar rats were distributed among four treatment groups: a standard low-fat diet group, a HF diet group, and two HF diet groups with a daily oral dose of ASE (100 or 200 mg/kg body weights) administered for 9 weeks. Daily energy intake, body weight, blood glucose levels and glucose tolerance, and insulin tolerance were evaluated. At the end of the study, organs, and tissues were collected and weighed for analysis, and blood samples were collected to determine the serum insulin levels and serum liver enzymes. Total phenolic and flavonoid contents and 2,2-Diphenyl-1-picrylhydrazyl free radical antioxidant activity of the ASE were evaluated. Oral administration of the low dose of ASE to HF diet-fed rats significantly reduced the long-term food intake and body weight gain without altering adiposity compared with untreated HF diet-fed rats. This outcome was accompanied by a significant improvement in insulin sensitivity and a reduction in fasting blood glucose (FBG) levels measured at weeks 6 and 9 of the study. The high dose of ASE had a short-term effect on body weight gain and food and caloric intake, and in the long-term, it improved FBG levels measured at weeks 6 and 9 of the study. The high dose of ASE resulted in hyperinsulinemia and high homeostatic model assessment for insulin resistance (HOMA-IR) value compared to healthy rats. Total phenolic and flavonoid contents were 74.9 ± 0.491 mg of gallic acid equivalent and 20.0 ± 0.091 mg quercetin equivalent per g of ASE, respectively. The antioxidant activity of ASE expressed as half-maximal inhibitory concentration (IC50) value was 8.43 ± 0.825 mg/mL. These data suggest that ASE can safely and potently reduce the development of insulin resistance induced by HF diet feeding and lowering body weight gain in a dose-dependent manner.

Dataset Information

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

Publications

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

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