Olive pomace juice(OPJ),a standardized byproduct of olive oil production containing>10%hydroxytyrosol,was investigated for its potential as a neuroprotective food ingredient against scopolamine-induced cognitive de...Olive pomace juice(OPJ),a standardized byproduct of olive oil production containing>10%hydroxytyrosol,was investigated for its potential as a neuroprotective food ingredient against scopolamine-induced cognitive decline in C57BL/6 mice.Oral administration of OPJ improved multiple aspects of learning and memory,including prolonged latency in the Passive Avoidance test,increased exploration in the Novel Object Recognition test,reduced escape latency in the Morris Water Maze,and enhanced working memory in the Radial Arm Maze.At the molecular level,OPJ activated the NRF2-HO-1 antioxidant pathway while suppressing NF-κB signaling,upregulated antioxidant enzymes,and reduced inflammatory mediators,with a significant increase in glutathione content.Importantly,OPJ stimulated the AMPKα-SIRT1-PGC1αsignaling axis,and enhanced the CREB-BDNF-TrkB pathway,thus supporting cellular energy homeostasis,synaptic plasticity,and neuronal survival.OPJ also increased the expression of tight junction proteins and BDNF,suggesting improved neuronal network stability.Neuropathological analyses further showed inhibition of tau phosphorylation,β-secretase expression,and acetylcholinesterase activity,and indicated elevated acetylcholine levels and protection of hippocampal neurons from scopolamine-induced injury.Collectively,these findings demonstrate that OPJ alleviates cognitive impairment through the coordinated regulation of oxidative stress,inflammation,and neurotrophic signaling.Notably,this study is the first to link the cognitive benefits of OPJ to the AMPKα-SIRT1-PGC1αand CREB-BDNF-TrkB pathways,highlighting its potential as a sustainable food-derived ingredient for neuroprotection with applications in functional foods and nutraceuticals.展开更多
基金supported by the Technology development Program(RS-2024-00427643)funded by the Ministry of SMEs and Startups(MSS,Korea).
文摘Olive pomace juice(OPJ),a standardized byproduct of olive oil production containing>10%hydroxytyrosol,was investigated for its potential as a neuroprotective food ingredient against scopolamine-induced cognitive decline in C57BL/6 mice.Oral administration of OPJ improved multiple aspects of learning and memory,including prolonged latency in the Passive Avoidance test,increased exploration in the Novel Object Recognition test,reduced escape latency in the Morris Water Maze,and enhanced working memory in the Radial Arm Maze.At the molecular level,OPJ activated the NRF2-HO-1 antioxidant pathway while suppressing NF-κB signaling,upregulated antioxidant enzymes,and reduced inflammatory mediators,with a significant increase in glutathione content.Importantly,OPJ stimulated the AMPKα-SIRT1-PGC1αsignaling axis,and enhanced the CREB-BDNF-TrkB pathway,thus supporting cellular energy homeostasis,synaptic plasticity,and neuronal survival.OPJ also increased the expression of tight junction proteins and BDNF,suggesting improved neuronal network stability.Neuropathological analyses further showed inhibition of tau phosphorylation,β-secretase expression,and acetylcholinesterase activity,and indicated elevated acetylcholine levels and protection of hippocampal neurons from scopolamine-induced injury.Collectively,these findings demonstrate that OPJ alleviates cognitive impairment through the coordinated regulation of oxidative stress,inflammation,and neurotrophic signaling.Notably,this study is the first to link the cognitive benefits of OPJ to the AMPKα-SIRT1-PGC1αand CREB-BDNF-TrkB pathways,highlighting its potential as a sustainable food-derived ingredient for neuroprotection with applications in functional foods and nutraceuticals.
