title: Echinacoside inhibits amyloid fibrillization of HEWL and protects against Aβ-induced neurotoxicity.
abstract: Amyloid protein depositions play crucial roles in a variety of degenerative disorders composing amyloidosis. There is a great interest in developing small molecule inhibitors of amyloidogenic processes. We examined the inhibitory effects of echinacoside (ECH) with different concentrations and at different fiber-forming stages in vitro utilizing the hen egg-white lysozyme (HEWL) model system. We also evaluated the antioxidant capacity of ECH by using elimination tests for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (HO) free radicals. We investigated the protection provided by ECH against neurotoxicity induced by β-amyloid protein (Aβ). Through spectroscopic analyses, electron microscopy, cell viability assay, and hemolysis assay, we found that ECH dose dependently inhibited HEWL aggregation, and this inhibition occurred in different fiber-forming stages. ECH could also scavenge the DPPH and OH free radicals in a concentration-dependent manner. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluoresceindiacetate (DCFH-DA) fluorescent measurement results indicated that ECH could increase viability of rat pheochromocytoma PC12 cells injured by Aβ and suppress the increase in intracellular reactive oxygen species (ROS) triggered by Aβ. The present study findings facilitate a better understanding of the interaction between ECH and amyloid-forming proteins and also shed light on the protection of ECH against amyloid fibril-induced neuronal cell death.
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China; Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, 169 West Changle Road, Xi'an 710032, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, People's Republic of China. Electronic address: yyswjb@fmmu.edu.cn.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry; D016716:PC12 Cells; D010851:Picrates / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001713:Biphenyl Compounds; D006027:Glycosides; D010851:Picrates; D020011:Protective Agents; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; C004931:1,1-diphenyl-2-picrylhydrazyl; C421864:hen egg lysozyme; D009113:Muramidase; C060297:echinacoside
keywords: Echinacoside; Hen egg-white lysozyme; β-Amyloid protein