Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-β Peptide Toxicity

Abstract

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-β peptide (Aβ) accumulation, where the soluble oligomers of Aβ (AβOs) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease. Lignans are compounds extracted from conifers and have several medicinal properties. Eudesmin (Eu) is an extractable lignan from the wood of Araucaria araucana, a native tree from Chile. This metabolite has shown a range of biological properties, including the ability to control inflammation and antibacterial effects. Objective: In this study, the neuroprotective abilities of Eu on synaptic failure induced by AβOs were analyzed. Methods: Using neuronal models, PC12 cells, and in silico simulations we evaluated the neuroprotective effect of Eu (30 nM) against the toxicity induced by AβOs. Results: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against AβOs toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the AβOs toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the Aβ aggregation process inducing a decrease in AβOs toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu. Conclusion: We believe that Eu represents a novel lead that reduces the Aβ toxicity, opening new research venues for lignans as neuroprotective agents.

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study

“…Recently, Mentese and colleagues reported that vanillic acid exhibited ovoprotective effects in a cisplatin-induced rat model of ovotoxicity by activating Nrf2 [ 37 ]. Furthermore, studies have shown that the renal protective effects of magnolin in rat kidney injury models are attributed to its antioxidative, anti-inflammatory, and antiapoptotic properties [ 51 , 52 ], while eudesmin (a tetrahydrofurofuranoid lignan) has been found to possess neuroprotective properties in an amyloid-β-induced model of Alzheimer’s disease [ 53 ]. These findings lead us to speculate that the ovoprotective effects of MFE may be attributed to the cytoprotective activities of vanillic acid, magnolin, and eudesmin.…”

An examination of Alzheimer’s disease and white matter from 1981 to 2023: a Bibliometric and visual analysis

“…At present, the journal boasts an impressive impact factor of 4. Distinguished by its thematic focus on AD pathogenesis and therapeutic interventions, the Journal of Alzheimer’s Disease has recently witnessed noteworthy investigations delving into the ramifications of compounds such as resveratrol, kaempferol, and Eduesmin on AD pathophysiology ( 29 – 32 ). In essence, the number of articles published by research collectives serves as a testament to their active engagement and contributions within a given scientific sphere.…”

“…Evidently, the United States' robust healthcare investments surpassing those of other nations potentially elucidate the concentration of AD and cerebral white matter research publications in this region (27,28). Moreover, it is notable that most collaborative efforts concerning AD and cerebral white matter are anchored in the United States, seamlessly (29)(30)(31)(32). In essence, the number of articles published by research collectives serves as a testament to their active engagement and contributions within a given scientific sphere.…”

Introduction to The Special Issue: Novel Molecular Pathways and Therapeutic Challenges in Neurodegenerative Diseases

“…In an article by Daly et al [15], they give insight into understanding the association with intervention; the Alzheimer's Disease-Associated Processes and Targets (ADAPT) ontology provides a new dimension to understanding novel neurodegenerative pathways. Furthermore, Castillo and colleagues [16] highlight the neuroprotective properties of eudesmin, a natural lignin from the tree Araucaria Araucana. This lignan prevents amyloid-␤ peptide toxicity in cell models and may lead to novel molecules in therapeutic intervention.…”