Examining the inhibitory potency of food additive fast green FCF against amyloid fibrillogenesis under acidic conditions

Abstract

More than thirty human proteins and/or peptides can fold incorrectly to form amyloid deposits associated with several protein aggregation diseases. No cure is currently available for treating these diseases. This work is aimed at examining the inhibitory potency of fast green FCF, a biocompatible dye, toward the fibrillogenesis/aggregation of lysozyme. As verified by ThT binding assay along with transmission electron microscopy, fast green FCF was observed to suppress the generation of lysozyme fibrils in a concentration-dependent manner. We next used circular dichroism absorption spectroscopy, ANS fluorescence spectroscopy, and SDS-PAGE to characterize the structural alterations in lysozyme samples upon the addition of fast green FCF. Furthermore, experiments with the addition of fast green FCF at different time points of incubation showed that fast green FCF also exhibited disaggregating activity against the preformed/existing lysozyme fibrils. We believe that the results from this study suggest a potential therapeutic role of biocompatible molecules in treating or preventing protein aggregation diseases.

Binding and Inhibitory Effect of the Dyes Amaranth and Tartrazine on Amyloid Fibrillation in Lysozyme

“…In this context, it is also pertinent to mention that several research groups have probed the inhibitory effect of small molecules on fibrillogenesis in LSZ under varying conditions. ,,− The inhibitory effect of many small molecules like aromatic polyphenols, − benzofurans, acridines, as well as flavones has been investigated. − The influence of several dyes like the food additive brilliant blue FCF, fast green FCF, brilliant blue G, methylene blue, , Congo red, , and its lipophilic analogue Chrysamine-G on fibrillogenesis has also been studied. Most of these molecules exhibited a concentration/dose dependent inhibitory action against fibrillogenesis in protein.…”

“…Most of these molecules exhibited a concentration/dose dependent inhibitory action against fibrillogenesis in protein. For example, the effect of the food additives brilliant blue FCF and fast green FCF on fibrillogenesis in LSZ was studied at varying molar ratios and both dyes showed a concentration dependent inhibitory influence on fibrillation. , The inhibitory effect of the nontoxic dietary pigment curcumin on fibrillogenesis in LSZ has also been investigated in the concentration range from 1 to 100 μM, and it was observed from ThT fluorescence emission assay (percentage reduction in ThT fluorescence) that curcumin inhibited fibrillogenesis more effectively at higher concentrations . On the basis of the same ThT fluorescence assay, the inhibitory potency of AMTH and TZ was found to be comparatively lower than that of curcumin at 25 and 100 μM concentrations, respectively.…”

Fast Green FCF Alleviates Pain Hypersensitivity and Down-Regulates the Levels of Spinal P2X4 Expression and Pro-inflammatory Cytokines in a Rodent Inflammatory Pain Model

“…Recently, the role of FGF in protein-aggregation has been investigated. FGF suppresses the generation of amyloid fibrils in lysosomes under acidic conditions, suggesting a potential role of FGF in preventing amyloid-aggregation diseases ( How et al, 2016 ). However, the biological action of FGF and the underlying mechanism in inflammatory pain has not been explored yet.…”

Inhibition of the formation of lysozyme fibrillar assemblies by the isoquinoline alkaloid coralyne

“…The far-UV CD spectra of HEWL showed an a-rich conformation (B35.90% a-helix, B15.10% b-sheet, B49% turns and unordered) which was characterized by a minimum at B208 nm and a negative shoulder at B222 nm before the advent of fibrillation (with or without COR) 22,105,106 With the increase in time there was a structural transition in HEWL which caused a prominent shift in its secondary structure to a b-sheet rich conformation. 22,72,106 After 9 h the CD spectrum of HEWL showed a marked change and was characterized by a well defined minimum at 221 nm. This is characteristic of the b-sheet rich conformation (B0.90% a-helix, B50.70% b-sheet, B48.40% turns and unordered).…”

“…Natural as well as synthetic small molecules capable of inhibiting fibrillation of various proteins/peptides are known. [18][19][20][21][22] Lysozyme is basically N-acetylmuramide glyconohydrolase which is a monomeric globular protein with 129 amino acid residues. It is found abundantly in various animal protective secretions and lymphatic tissues.…”