Inhibition of fibrillation of human γD-crystallin by a flavonoid morin

Abstract

To inhibit the formation of amyloid fibrils by human gamma D-crystallin (HGD), a series of four flavonoids (quercertin, rutin, morin and hesperetin) was tested. Only morin had demonstrated significant inhibition of HGD fibrillation. Results from fluorimetric assay techniques (using thioflavin T and ANS), FTIR, circular dichroism and microscopic imaging (fluorescence microscopy and transmission electron microscopy) confirmed HGD fibrillation inhibition by morin. HGD-morin complex formation at ground state resulted tryptophan fluorescence quenching through static mechanism, which was also confirmed by determining the excited-state life time of HGD tryptophan residues. Forster resonance energy transfer occurs from HGD to morin. Synchronous, three-dimensional fluorescence, FTIR and circular dichroism results suggest that major changes in HGD conformation did not occur on binding with morin. The interactions between HGD and morin involve hydrogen bonding and/or van der Waals forces. Docking predictions also support experimental results.