@article{uneatlantico17569,
          author = {Jose M. Romero?Marquez and Mar{\'i}a D. Navarro?Hortal and Alfonso Varela?L{\'o}pez and Rub{\'e}n Calder{\'o}n Iglesias and Juan G. Puentes and Francesca Giampieri and Maurizio Battino and Cristina S{\'a}nchez?Gonz{\'a}lez and Jianbo Xiao and Roberto Garc{\'i}a?Ruiz and Sebasti{\'a}n S{\'a}nchez and Tamara Y. Forbes?Hern{\'a}ndez and Jos{\'e} L. Quiles},
            year = {2025},
         journal = {Food Frontiers},
           title = {Olive Leaf Extracts With High, Medium, or Low Bioactive Compounds Content Differentially Modulate Alzheimer's Disease via Redox Biology},
           month = {Abril},
        keywords = {acetylcholinesterase (AChE) {\ensuremath{|}} by-product {\ensuremath{|}} Caenorhabditis elegans {\ensuremath{|}} cyclooxygenase-2 (COX-2) {\ensuremath{|}} ferric reducing antioxidant power (FRAP) {\ensuremath{|}}glutathione (GSH) {\ensuremath{|}} phytochemical},
             url = {http://repositorio.uneatlantico.es/id/eprint/17569/},
        abstract = {Alzheimer's disease (AD) involves {\ensuremath{\beta}}-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 A{\ensuremath{\beta}} 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 A{\ensuremath{\beta}} 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.}
}