Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology

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Auteurs principaux: Jose M. Romero‐Marquez, María D. Navarro‐Hortal, Alfonso Varela‐López, Rubén Calderón‐Iglesias, Juan G. Puentes, Francesca Giampieri, Maurizio Battino, Cristina Sánchez‐González, Jianbo Xiao, Roberto García‐Ruiz, Sebastián Sánchez, Tamara Y. Forbes‐Hernández, José L. Quiles
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author Jose M. Romero‐Marquez
María D. Navarro‐Hortal
Alfonso Varela‐López
Rubén Calderón‐Iglesias
Juan G. Puentes
Francesca Giampieri
Maurizio Battino
Cristina Sánchez‐González
Jianbo Xiao
Roberto García‐Ruiz
Sebastián Sánchez
Tamara Y. Forbes‐Hernández
José L. Quiles
author_facet Jose M. Romero‐Marquez
María D. Navarro‐Hortal
Alfonso Varela‐López
Rubén Calderón‐Iglesias
Juan G. Puentes
Francesca Giampieri
Maurizio Battino
Cristina Sánchez‐González
Jianbo Xiao
Roberto García‐Ruiz
Sebastián Sánchez
Tamara Y. Forbes‐Hernández
José L. Quiles
Jose M. Romero‐Marquez
María D. Navarro‐Hortal
Alfonso Varela‐López
Rubén Calderón‐Iglesias
Juan G. Puentes
Francesca Giampieri
Maurizio Battino
Cristina Sánchez‐González
Jianbo Xiao
Roberto García‐Ruiz
Sebastián Sánchez
Tamara Y. Forbes‐Hernández
José L. Quiles
collection Wiley Open Access
contents Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology Jose M. Romero‐Marquez María D. Navarro‐Hortal Alfonso Varela‐López Rubén Calderón‐Iglesias Juan G. Puentes Francesca Giampieri Maurizio Battino Cristina Sánchez‐González Jianbo Xiao Roberto García‐Ruiz Sebastián Sánchez Tamara Y. Forbes‐Hernández José L. Quiles Food Frontiers ABSTRACTAlzheimer's disease (AD) involves β‐amyloid plaques and tau hyperphosphorylation, driven by oxidative stress and neuroinflammation. Cyclooxygenase‐2 (COX‐2) and acetylcholinesterase (AChE) activities exacerbate AD pathology. Olive leaf (OL) extracts, rich in bioactive compounds, offer potential therapeutic benefits. This study aimed to assess the anti‐inflammatory, anti‐cholinergic, and antioxidant effects of three OL extracts (low, mid, and high bioactive content) in vitro and their protective effects against AD‐related proteinopathies in Caenorhabditis elegans models. OL extracts were characterized for phenolic composition, AChE and COX‐2 inhibition, as well as antioxidant capacity. Their effects on intracellular and mitochondrial reactive oxygen species (ROS) were tested in C. elegans models expressing human Aβ and tau proteins. Gene expression analyses examined transcription factors (DAF‐16, skinhead [SKN]‐1) and their targets (superoxide dismutase [SOD]‐2, SOD‐3, GST‐4, and heat shock protein [HSP]‐16.2). High‐OL extract demonstrated superior AChE and COX‐2 inhibition and antioxidant capacity. Low‐ and high‐OL extracts reduced Aβ aggregation, ROS levels, and proteotoxicity via SKN‐1/NRF‐2 and DAF‐16/FOXO pathways, whereas mid‐OL showed moderate effects through proteostasis modulation. In tau models, low‐ and high‐OL extracts mitigated mitochondrial ROS levels via SOD‐2 but had limited effects on intracellular ROS levels. High‐OL extract also increased GST‐4 levels, whereas low and mid extracts enhanced GST‐4 levels. OL extracts protect against AD‐related proteinopathies by modulating oxidative stress, inflammation, and proteostasis. High‐OL extract showed the most promise for nutraceutical development due to its robust phenolic profile and activation of key antioxidant pathways. Further research is needed to confirm long‐term efficacy. 10.1002/fft2.70013 http://creativecommons.org/licenses/by-nc-nd/4.0/
doi_str_mv 10.1002/fft2.70013
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id wiley_oa_10_1002_fft2_70013
institution Wiley Open Access
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publishDate 2025
publisher Wiley
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spellingShingle Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology
Jose M. Romero‐Marquez
María D. Navarro‐Hortal
Alfonso Varela‐López
Rubén Calderón‐Iglesias
Juan G. Puentes
Francesca Giampieri
Maurizio Battino
Cristina Sánchez‐González
Jianbo Xiao
Roberto García‐Ruiz
Sebastián Sánchez
Tamara Y. Forbes‐Hernández
José L. Quiles
Food Frontiers
Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology Jose M. Romero‐Marquez María D. Navarro‐Hortal Alfonso Varela‐López Rubén Calderón‐Iglesias Juan G. Puentes Francesca Giampieri Maurizio Battino Cristina Sánchez‐González Jianbo Xiao Roberto García‐Ruiz Sebastián Sánchez Tamara Y. Forbes‐Hernández José L. Quiles Food Frontiers ABSTRACTAlzheimer's disease (AD) involves β‐amyloid plaques and tau hyperphosphorylation, driven by oxidative stress and neuroinflammation. Cyclooxygenase‐2 (COX‐2) and acetylcholinesterase (AChE) activities exacerbate AD pathology. Olive leaf (OL) extracts, rich in bioactive compounds, offer potential therapeutic benefits. This study aimed to assess the anti‐inflammatory, anti‐cholinergic, and antioxidant effects of three OL extracts (low, mid, and high bioactive content) in vitro and their protective effects against AD‐related proteinopathies in Caenorhabditis elegans models. OL extracts were characterized for phenolic composition, AChE and COX‐2 inhibition, as well as antioxidant capacity. Their effects on intracellular and mitochondrial reactive oxygen species (ROS) were tested in C. elegans models expressing human Aβ and tau proteins. Gene expression analyses examined transcription factors (DAF‐16, skinhead [SKN]‐1) and their targets (superoxide dismutase [SOD]‐2, SOD‐3, GST‐4, and heat shock protein [HSP]‐16.2). High‐OL extract demonstrated superior AChE and COX‐2 inhibition and antioxidant capacity. Low‐ and high‐OL extracts reduced Aβ aggregation, ROS levels, and proteotoxicity via SKN‐1/NRF‐2 and DAF‐16/FOXO pathways, whereas mid‐OL showed moderate effects through proteostasis modulation. In tau models, low‐ and high‐OL extracts mitigated mitochondrial ROS levels via SOD‐2 but had limited effects on intracellular ROS levels. High‐OL extract also increased GST‐4 levels, whereas low and mid extracts enhanced GST‐4 levels. OL extracts protect against AD‐related proteinopathies by modulating oxidative stress, inflammation, and proteostasis. High‐OL extract showed the most promise for nutraceutical development due to its robust phenolic profile and activation of key antioxidant pathways. Further research is needed to confirm long‐term efficacy. 10.1002/fft2.70013 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology
topic Food Frontiers
url https://iadns.onlinelibrary.wiley.com/doi/10.1002/fft2.70013