Aggregation of α-synuclein (αSN) is implicated in neuronal degeneration in Parkinson’s disease and has prompted searches for natural compounds inhibiting αSN aggregation and reducing its tendency to form toxic oligomers. Oil from the olive tree (Olea europaea L.) represents the main source of fat in the Mediterranean diet and contains variable levels of phenolic compounds, many structurally related to the compound oleuropein. Here, using αSN aggregation, fibrillation, size-exclusion chromatography–multi-angle light scattering (SEC-MALS)-based assays, and toxicity assays, we systematically screened the fruit extracts of 15 different olive varieties to identify compounds that can inhibit αSN aggregation and oligomer toxicity and also have antioxidant activity. Polyphenol composition differed markedly among varieties. The variety with the most effective antioxidant and -aggregation activities, Koroneiki, combined strong inhibition of αSN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic αSN oligomers. Fractionation of the Koroneiki extract identified oleuropein aglycone, hydroxy oleuropein aglycone, and oleuropein as key compounds responsible for the differences in inhibition across the extracts. These phenolic compounds inhibited αSN amyloidogenesis by directing αSN monomers into small αSN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences in the level of effective phenolic compounds in different olive varieties, insights that have implications for long-term human health.

Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]⁻ equivalent to C₆₄H₁₀₄O₃₃ and the putatively found active metabolite at m/z 1283.58 [M + formic-H]⁻ corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM.

Several approaches have been dedicated to activate the cryptic gene clusters in the genomes of actinomycetes for the targeted discovery of new fascinating biomedical lead structures. In the current study, N-acetylglucosamine was used to maximize the chemical diversity of sponge-derived actinomycete Actinokineospora spheciospongiae sp. nov. HR–ESI–MS was employed for dereplication study and orthogonal partial least square-discriminant analysis was applied to evaluate the HR–ESI–MS data of the different fractions. As a result, two new fridamycins H (1) and I (2), along with three known compounds actinosporin C (3), D (4), and G (5) were isolated from the solid culture of sponge-associated actinomycete Actinokineospora spheciospongiae sp. nov., elicited with N-acetylglucosamine. Characterization of the isolated compounds was pursued using mass spectrometry and NMR spectral data. Fridamycin H (1) exhibited significant growth inhibitory activity towards Trypanosoma brucei strain TC221. These results highlight the potential of elicitation in sponge-associated actinomycetes as an effective strategy for the discovery of new anti-infective natural products.