Today, Alzheimer’s disease (AD)—the most common neurodegenerative disorder, which affects 50 million people—remains incurable. Several studies suggest that one of the main pathological hallmarks of AD is the accumulation of abnormal amyloid beta (Aβ) aggregates; therefore, many therapeutic approaches focus on anti-Aβ aggregation inhibitors. Taking into consideration that plant-derived secondary metabolites seem to have neuroprotective effects, we attempted to assess the effects of two flavones—eupatorin and scutellarein—on the amyloidogenesis of Aβ peptides. Biophysical experimental methods were employed to inspect the aggregation process of Aβ after its incubation with each natural product, while we monitored their interactions with the oligomerized Aβ through molecular dynamics simulations. More importantly, we validated our in vitro and in silico results in a multicellular organismal model—namely, Caenorhabditis elegans—and we concluded that eupatorin is indeed able to delay the amyloidogenesis of Aβ peptides in a concentration-dependent manner. Finally, we propose that further investigation could lead to the exploitation of eupatorin or its analogues as potential drug candidates.

Alzheimer’s disease (AD) is the most common form of dementia. Given the link between oxidative stress and AD, many studies focus on the identification of natural antioxidants against AD. Although their antioxidant capacity is important, increasing data suggest that additional activities are related to their beneficial effects, including properties against amyloid beta (Aβ) aggregation. Sideritis spp. (mountain tea) extracts possess not only antioxidant activity but also other bioactivities that confer neuroprotection. Although various Sideritis spp. extracts have been extensively studied, there are scarce data on S. clandestina subsp. peloponnesiaca (SCP) phytochemical composition and neuroprotective potential, while nothing is known of the responsible compounds. Given that SCP is a weaker antioxidant compared to other Sideritis spp., here, we investigated its potential beneficial properties against Aβ aggregation. We characterized different SCP extracts and revealed their anti-aggregation activity by taking advantage of established C. elegans AD models. Importantly, we identified two pure compounds, namely, sideridiol and verbascoside, being responsible for the beneficial effects. Furthermore, we have revealed a potential anti-Aβ aggregation mechanism for sideridiol. Our results support the use of mountain tea in the elderly against dementia and demonstrate the activity of sideridiol against Aβ aggregation that could be exploited for drug development.

Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease–protein–drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein–protein, protein–drug, and disease–drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition.