The Anti-amyloidogenic effect of natural product extracts on amyloid-like fibril formation of trypsin in aqueous organic solvents

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The formation of amyloid fibrils has been associated with several human diseases. The appearance of amyloid aggregation is an indicator of different central nervous system neurological disorders and neurodevelopmental diseases, which affect the brain and peripheral tissues. The misfolding and aggregation of proteins cause a large number of different neurodegenerative diseases. Amyloid is a generic structural form of the polypeptide chain and most proteins can form amyloid-like fibrils under proper conditions. Natural product extracts contain important bioactive compounds without undesirable side effects, which are necessary for the prevention and cure of various diseases. 52 phenolic compounds were identified in culinary herbs and spices. The aromatic rings of polyphenols may competitively interact with aromatic residues in amyloidogenic proteins, prevent the π-π interaction and block the self-assembly process. The phenolic hydroxyls of polyphenols may inhibit amyloid fibril formation via binding the hydrophobic residues in amyloidogenic proteins. Here we report the inhibitory effect of some natural product extracts on the formation of amyloid fibrils using trypsin as a model protein in aqueous ethanol. Inhibition of aggregation and fibrillation of trypsin was determined based on turbidity measurement, aggregation kinetics assay, amyloid specific dye Congo red (CR), fouriertransformed infrared (FTIR) spectroscopy, electronic circular dicroism (ECD) and transmission electron microscopy (TEM). The experiments revealed that great anti-fibrillation activity was exerted by chili extract, P. ginseng extract, grapefruit seed extract, peppermint extract, Eduscho coffee extract, and Egri bikavér red wine. It was found that the amount of fibril formation was greatly reduced with increasing concentration of extracts and the inhibitory effect is dose-dependent.

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