Metabolomic profiling of myrtle leaves extracts and evaluation of their anti-amyloidogenic activity against Aβ1-42 peptide

Neurodegenerative disorders, such as Alzheimer’s disease (AD), are characterized by the accumulation of extracellular insoluble aggregates of misfolded proteins, notably the Amyloid-β (Aβ) peptide, that lead to synaptic dysfunction and nerve cell death [1]. Among the strategies aimed at counteracting Aβ aggregation, natural polyphenolic compounds, particularly flavonoids and catechins, have shown promising anti-amyloidogenic and neuroprotective properties [2-4]. Myrtle (Myrtus communis) is an evergreen aromatic plant, historically used in cooking and liqueur production. While the leaves are often considered a waste product, they could represent a valuable resource, as they are known to contain a variety of bioactive compounds [5]. Here we describe the characterization of hydro-alcoholic extracts of myrtle leaves using a combined NMR and LC-HRMS metabolomic approach. Both total extracts and phenolic-enriched fraction were analyzed, revealing the presence of several bioactive compounds, including flavonoids, hydrolysable tannins, myrtucommulones, organic acids, and glycosylated phenolic acids. The biological activity of myrtle leaves extracts was evaluated at first by binding assays employing STD-NMR to confirm direct binding interactions between selected extract compounds and Aβ1-42 oligomers. Furthermore, myrtle extracts anti-amyloidogenic activity against Aβ1-42 peptide was investigated by other complementary approaches, such as Fourier-transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM), which provided structural and morphological evidence supporting a significant alteration in Aβ1-42 aggregation pathway after incubation with myrtle extracts. Our data suggest that myrtle bioactive compounds could represent promising tools for the safe and sustainable prevention and treatment of neurodegenerative disorders by exploiting the combination of their antioxidant, anti-inflammatory, and anti-amyloidogenic properties [2] in the modulation of early molecular events linked to neurodegeneration.