title: Anti-fibrillation propensity of a flavonoid baicalein against the fibrils of hen egg white lysozyme: potential therapeutics for lysozyme amyloidosis.
abstract: More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3 M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20-fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in Congo red assay and appearance of a network of long rope-like fibrils in transmission electron microscope (TEM) analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose-dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150-μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 and 450 nm, respectively, together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.
authors.affiliation: a Department of Biochemistry, Faculty of Life Sciences , Aligarh Muslim University , Aligarh , India.
authors.forename: Naveed Ahmad
authors.initials: NA
authors.lastname: Fazili
authors.affiliation: b Department of Chemistry, Faculty of Sciences , Aligarh Muslim University , Aligarh , India.
authors.forename: Imtiyaz Ahmad
authors.initials: IA
authors.lastname: Bhat
authors.affiliation: a Department of Biochemistry, Faculty of Life Sciences , Aligarh Muslim University , Aligarh , India.
authors.forename: Waseem Feeroze
authors.initials: WF
authors.lastname: Bhat
authors.affiliation: a Department of Biochemistry, Faculty of Life Sciences , Aligarh Muslim University , Aligarh , India.
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D055808:Drug Discovery; D044950:Flavanones / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000648:ultrastructure; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D044950:Flavanones; D059808:Polyphenols; C006680:baicalein; C421864:hen egg lysozyme; D009113:Muramidase
keywords: Congo red; amyloid fibrils; baicalein; negative ellipticity; therapeutics