Brazilian Medicinal Plants with Antiamyloidogenic Activity

Amyloid fibrillation is a process involved in a large set of pathologies, including diabetes and Alzheimer's. Although Brazil has a large biodiversity, until now there are no records regarding Brazilian plants as a source for inhibitors of amyloid fibrillation of amylin. Since one of the great concerns involving amylin is the toxicity of its aggregates, the aim of this study was to investigate the inhibitory activity of 68 Brazilian plant extracts and isolated specialized metabolites against the amyloid aggregation of amylin using mass spectrometry as a tool to characterize the chemical profile of the most active ones. Amylin kinetics assays were performed based on ThT monitoring, using curcumin as a control for aggregation inhibition. The most active extracts were analyzed by ultra-performance liquid chromatography coupled to mass spectrometry and the data processed using different workflows for dereplication. Chemometric tools such principal components analysis and partial least square discriminant analysis (PLS-DA) were used for data analysis. From the active Struthanthus acuminatus (syn. Struthanthus concinnus) and S. marginatus, hexane extracts 3-O-n-acyl-lup-20(29)-en-3 beta, 7 beta,15 alpha-triol, taraxerol, and obtusifoliol as well as other triterpene and steroid mixtures were isolated and evaluated towards the amyloid aggregation of amylin. However, their activities were not as satisfactory as the original extracts, indicating that they are not likely to embody the whole activity found with the extract. Fifteen, out of the 68 extracts tested, showed promising activity against amylin aggregation, 5 of them being the most active among the tested extracts, reducing the increase in fluorescence to a minimal level. By PLS-DA analysis, four features were revealed as potential discriminant of the species evaluated. These data demonstrate the potential for Brazilian flora as a source in the search for substances capable of reducing amyloid fibrillation.