Evaluation of polyphenols as possible therapeutics for amyloidoses: Comparative analysis of Kaempferol and Catechin

Several mammalian proteins fold abnormally under non physiological conditions, to form pathological deposits that are associated with many degenerative diseases. In vitro variation of solvent conditions and pH can lead to partial unfolding and subsequent fibril formation. In the present study, we examined the effects of low pH on goat brain cystatin (GBC) with a focus on amyloid fibril formation. The results demonstrate that GBC can form amyloid like fibrils at pH 3.0. Moreover this study is aimed at exploring the inhibitory activity of polyphenols, Kaempferol (KM) and Catechin (CA) against the fibrillation of GBC. Using fluorescence spectroscopic analysis with Thioflavin T, CD and electron microscopic studies, anti-fibrillation effects of polyphenols, KM and CA were analyzed. The study also revealed that KM and CA produced a concentration dependent anti-fibrillogenic effects with KM producing more pronounced effect compared to CA. The study proposed a mechanistic approach assuming structural constraints and specific aromatic interactions of polyphenols with 13 sheets of GBC fibrils. (C) 2015 Elsevier B.V. All rights reserved.