eprintid: 17569 rev_number: 8 eprint_status: archive userid: 2 dir: disk0/00/01/75/69 datestamp: 2025-04-09 23:30:12 lastmod: 2025-04-09 23:30:13 status_changed: 2025-04-09 23:30:12 type: article metadata_visibility: show creators_name: Romero‐Marquez, Jose M. creators_name: Navarro‐Hortal, María D. creators_name: Varela‐López, Alfonso creators_name: Calderón Iglesias, Rubén creators_name: Puentes, Juan G. creators_name: Giampieri, Francesca creators_name: Battino, Maurizio creators_name: Sánchez‐González, Cristina creators_name: Xiao, Jianbo creators_name: García‐Ruiz, Roberto creators_name: Sánchez, Sebastián creators_name: Forbes‐Hernández, Tamara Y. creators_name: Quiles, José L. creators_id: creators_id: creators_id: creators_id: ruben.calderon@uneatlantico.es creators_id: creators_id: francesca.giampieri@uneatlantico.es creators_id: maurizio.battino@uneatlantico.es creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: jose.quiles@uneatlantico.es title: Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology ispublished: pub subjects: uneat_sn divisions: uneatlantico_produccion_cientifica divisions: uninimx_produccion_cientifica full_text_status: public keywords: acetylcholinesterase (AChE) | by-product | Caenorhabditis elegans | cyclooxygenase-2 (COX-2) | ferric reducing antioxidant power (FRAP) |glutathione (GSH) | phytochemical abstract: Alzheimer'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. date: 2025-04 publication: Food Frontiers id_number: doi:10.1002/fft2.70013 refereed: TRUE issn: 2643-8429 official_url: http://doi.org/10.1002/fft2.70013 access: open language: en citation: Artículo Materias > Alimentación <http://repositorio.unini.edu.mx/view/subjects/uneat=5Fsn.html> Universidad Europea del Atlántico > Investigación > Producción Científica <http://repositorio.unini.edu.mx/view/divisions/uneatlantico=5Fproduccion=5Fcientifica.html> Universidad Internacional Iberoamericana México > Investigación > Artículos y libros <http://repositorio.unini.edu.mx/view/divisions/uninimx=5Fproduccion=5Fcientifica.html> Abierto Inglés Alzheimer'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. metadata Romero‐Marquez, Jose M.; Navarro‐Hortal, María D.; Varela‐López, Alfonso; Calderón Iglesias, Rubén; Puentes, Juan G.; Giampieri, Francesca; Battino, Maurizio; Sánchez‐González, Cristina; Xiao, Jianbo; García‐Ruiz, Roberto; Sánchez, Sebastián; Forbes‐Hernández, Tamara Y. y Quiles, José L. mail SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, ruben.calderon@uneatlantico.es, SIN ESPECIFICAR, francesca.giampieri@uneatlantico.es, maurizio.battino@uneatlantico.es, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, SIN ESPECIFICAR, jose.quiles@uneatlantico.es <http://repositorio.unini.edu.mx/id/eprint/17569/1/Food%20Frontiers%20-%202025%20-%20Romero%E2%80%90Marquez%20-%20Olive%20Leaf%20Extracts%20With%20High%20%20Medium%20%20or%20Low%20Bioactive%20Compounds%20Content.pdf> (2025) Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology. Food Frontiers. ISSN 2643-8429 document_url: http://repositorio.unini.edu.mx/id/eprint/17569/1/Food%20Frontiers%20-%202025%20-%20Romero%E2%80%90Marquez%20-%20Olive%20Leaf%20Extracts%20With%20High%20%20Medium%20%20or%20Low%20Bioactive%20Compounds%20Content.pdf