Interaction, inhibition and disruption of lysozyme fibrillar aggregates by the plant alkaloid berberine.

This study investigated the interaction and impact of berberine, a pharmacologically important natural alkaloid, on lysozyme amyloidosis with the aim to develop effective anti-amyloidogenic agents. Interaction between berberine and lysozyme was analyzed using both theoretical and experimental tools to unleash its anti-amyloidogenic potency. The intrinsic fluorescence of lysozyme was quenched by berberine through static mechanism, indicating the presence of single binding site predominantly involving TRP residues. Complexation with berberine caused microenvironmental and conformational changes in lysozyme as shown by synchronous and 3D fluorescence spectroscopic analysis. Molecular docking and dynamic simulation study revealed the probable binding site and pharmacokinetics involved in lysozyme-berberine complexation. Berberine significantly inhibited lysozyme fibrillation which was confirmed by Thioflavin T, Congo red, Nile red and ANS assays. FTIR and circular dichroism studies revealed that berberine reduced β-sheet content of lysozyme fibrillar samples, indicating inhibition of fibril formation. Additionally, berberine can degrade pathogenic mature fibril as well. Amyloid inhibition and defibrillation was visualised by atomic force microscopy.