title: Hematoxylin Inhibits Amyloid β-Protein Fibrillation and Alleviates Amyloid-Induced Cytotoxicity.
abstract: Accumulation and aggregation of amyloid β-protein (Aβ) play an important role in the pathogenesis of Alzheimer's disease. There has been increased interest in finding new anti-amyloidogenic compounds to inhibit Aβ aggregation. Herein, thioflavin T fluorescent assay and transmission electron microscopy results showed that hematoxylin, a natural organic molecule extracted from Caesalpinia sappan, was a powerful inhibitor of Aβ42 fibrillogenesis. Circular dichroism studies revealed hematoxylin reduced the β-sheet content of Aβ42 and made it assemble into antiparallel arrangement, which induced Aβ42 to form off-pathway aggregates. As a result, hematoxylin greatly alleviated Aβ42-induced cytotoxicity. Molecular dynamics simulations revealed the detailed interactions between hematoxylin and Aβ42. Four binding sites of hematoxylin on Aβ42 hexamer were identified, including the N-terminal region, S8GY10 region, turn region, and C-terminal region. Notably, abundant hydroxyl groups made hematoxylin prefer to interact with Aβ42 via hydrogen bonds. This also contributed to the formation of π-π stacking and hydrophobic interactions. Taken together, the research proved that hematoxylin was a potential agent against Aβ fibrillogenesis and cytotoxicity.
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.|College of Biotechnology and National and Local United Engineering Lab of Metabolic Control Fermentation Technology, Tianjin University of Science & Technology , Tianjin 300457, P. R. China.
authors.forename: Fufeng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, P. R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dong
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029911:Caesalpinia / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D006416:Hematoxylin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D066329:Protein Aggregates / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D006416:Hematoxylin